Brevet FR3087130A1 — publié le 20200417

Description Title of Invention: SYSTEMS AND METHODS FOR DE- LIVERING A POLYMERIC MATERIAL TO A TREATMENT SITE During a Radio Frequency Ablation Procedure Cross-reference to related applications 100011 This application daims priority to U.S. Provisional Application No. 62/745,652, filed October 15, 2018, which is herein incorporated hy referenced in its entirety. Technical Field 100021 The present disclosure relates to a temperature-controlled system for delivering a stimuli-responsive biomaterial to a treatment site. Background Art [0003] Pain in the knccs, hip, or back may manifcst itsclf to such a high degrec that the patient' s quality of lift is grcatly diminishcd. In such cases, a physicien may perform an electrosurgical procedure applying high frequency radiofrequency (RF) energy to treat, cut, ablate or coagulais tissue structures including neural tissue. In this minimally invasive procedure, a probe is inserted into a patient's body and placed at the nerve site responsible for the pain. High lrequency energy is delivered to the region of tissue from an energy source such as a generator via an active electrode of the probe. The resistance of tissue, located proximate the active electrode of the probe, to the high frequency energy causes the tissue temperature to rise and a lesion is formed at the nerve site. While this desyncing of the nerve provides the desired pain relief, often, the tissue proximate to the probe heats up l'aster Chan tissue farther away from the probe limiting the size of the lesion. [0004] Following a radiofrequency ablation (RFA) procedure, angiogenesis will begin at the ablation site. This is a typical response for nerve tissue that has undergone catastrophic damage. However, due to the destructive nature of RFA therapies, the nerve is unable to sync with its pre-ablation downstream counterpart. As a result, the distal/ downstream nerve site will degrade from a process known as Wallerian degradation. Wallerian degradation prevents the proper re-growth between the two sites and results in the nerve structure at the ablation site growing in an uncontrolled marner known as a growth cone. It is hypothesized that this process is responsible for the pain felt by patients several months to years alter the RFA procedure. Angiogenesis can be manipulated by stopping or slowing the regrowth of the nerve tissue. This requires administering a chemical, hiological, or comhination of growth antagonist to the nerve ablation site. However, several drawhacks exist for this approach, including: the lodstics needed to place the growth inhihitor molecule(s), regulate the release of the 2 molecule(s), and sustained release of the growth inhibitor molecule(s) at the ablation site. histead of prohibiting nerve regrowth, the innovative approach described herein comprises mitigating and manipulating nerve growth at the ablation site to prevent the formation of an unregulated growth cone and further delay the return of pain for the recipients of RFA. [0005] As described in co-pending U.S. Application No. titled "Compositions, Systems, Kits and Methods for Neural Ablation" (Attorney Docket No. 10964-006US1) filed concurrently herewith and incorporatcd herein hy reference, Nomatcrials can be applied proximatelover the lesion and/or nerve ablation site during a RF procedure to manipulate and mitigatc nerve growth. The layer of biomatcrial can also serve to provide a physical barder that prevents immune development. These biomatcrials can be provided at the treatment site during/following the RF procedure and would benefit from the claimed delivery system. In some examples, the biomaterial comprises a stimuli-responsive biocompatiblc polymer, e.g., a thermoresponsive polymcr, that must be cooled to its liquid phase temperature for delivery through a syringc and/or introducer cannula. As the polymcr warms within the body it solidifies to providc a physical barder between the lesions site and surrounding tissue. Accordingly, a need in the art exists for a coolcd syringe that can maintain the temperature of the polymer below its liquid-solid phase transition temperature. In other examples, the biornaterial comprises a crosslinkable biomaterial fortned from a first precursor and a second precursor which react in situ to fonn a polymeric matrix. In some of these embodiments, the first precursor and the second precursor must be separately stored prior to being combined at the treatment site. Accordingly, a need in the art exils for a double ban-el delivery system that maintains the first precursor and the second precursor in separate volumes before combining at the treatment site and/or in the delivery cannula. Summary of Invention [0006] Systems and mcthods for delivering a biomaterial to a trcatmcnt site arc described herein. An example temperature-controlled system for del ivering a stimuli-rcsponsivc biomaterial to a trcatmcnt site can include a syringe that maintains a thermoresponsivc polymer liquid contained therein at a temperature below its liquid-solid phase transition temperature. The syringe can include a body defining a volume for containing a thermoresponsive polymer liquid, a distal end of the body includes a delivery tip, and a plunger sized and configured to move within the volume of the body to convey the thermoresponsive polymer liquid through the delivery tip. The body of the syringe can include a cooling mechanism for maintaining an interior surface of the body at a temperature below the liquid-solid phase transition temperature of the ther- 3 moresponsive polymer liquid. Thc cooling mcchanism can includc an insulativc matcrial provided around the hody of the syringc. The hody of the syringc can also be formcd from a double wall vacuum insulatcd matcrial. The cooling mcchanism can also includc a cooling pad couplcd to the exterior of the hody of the syringc. The cooling mcchanism can also includc a chillcd water system where a volume of chillcd watcr is flowed around the hody of the syringc. The cooling mcchanism can also includc a thermoclectric coolcr. [0007] The temperature-controlled system can also includc an clongated introduccr cannula including a central channel sized and configurcd to receive the delivery tip of the syringc. The system can further includc a cooled radiofrequency (RF) probe sized for insertion into the central channel of the introduccr cannula, the cooled RF probe being configurcd to circulate watcr at a temperature that maintains the introduccr cannula at a temperature bclow the liquid-sol id phase transition temperature of the thermoresponsive polymer liquid. Thc introduccr cannula can includc at least one of an insulative matcrial providcd around the introducer cannula, a double wall vacuum insulatcd matcrial, a cooling pad couplcd to the introduccr cannula, a thermoclectric coolcr, or a chillcd water system for flowing a volume of chillcd water around the introduccr cannula. [0008] The temperature-controlled system can maintain an interior surface of the hody of the syringc at a temperature below about hody temperature. The intcrior surface of the body of the syringe can be maintained at a temperature between about 28°C and about 42°C. [0009] The temperature-controlled system can maintain an interior surface of the body of the syringe at a temperature below about room temperature. The interior surface of the body of the syringe can be maintained at a temperature between about 19°C and about 25°C. [0010] The temperature-controlled system can maintain the syringe or the thermoresponsive polymer at a temperature below about 20°C. [0011] The temperature-controlled system can maintain the syringe or the thermoresponsive polymer at a temperature at or below about 4°C. [0012] An example system for delivering a biomaterial to a radio frequency ablation treatment site can include a syringe and an elongated introducer cannula. The syringe can include a body defining a volume for containing a biomaterial, a distal end of the body includes a delivery tip, and a plunger sized and configured to move within the volume of the body to convey the biomaterial through the delivery tip. The elongated introducer cannula can include a central channel sized and configured to receive the delivery tip of the syringe, and an engagement feature provided at a proximal end of the introducer cannula for coupling with a corresponding engagement feature provided at a distal end of the syringe. The syringc and introducer cannula can bc movable between an unlocked and locked configuration, where in the unlocked configuration the syringc and introduccr cannula engagement features arc not couplcd, and where in the locked configuration the syringe and introduccr engagement features arc couplcd. In the unlocked configuration axial movcment of the plunger within the volume of the body can he prohibitcd, preventing flow of the hiomaterial through the delivery tip. In the locked configuration axial movement of the plunger within the volume can bc permitted thereby providing flow of the hiomaterial through the delivery tip and into the introduccr cannula. The system can furthcr includc a restraint mcchanism couplcd to the plunger, wherein the restraint mcchanism is configured to restrict axial movement of the plunger within the volume. Thc engagement fcaturc providcd at the proximal end of the introduccr cannula can he a female Lucr fitting, and the engagement fcaturc providcd at the distal end of the syringe can he a male Lucr fitting, where rotational movement between the male and female Lucr fittings results in secured coupling between the introduccr cannula and the syringc. The engagement fcaturc providcd at the proximal end of the introduccr cannula can includc at least one of a recess, a projection, a tapered surface for press fitting with the syringc, a clip, a thrcad, a bayonct mount, and the engagement fcaturc providcd at the distal end of the syringc can includc a corresponding at least one of a projection, a recess, a tapered surface for press fitting with the introducer cannula, a clip, a thread, and a bayonet mount, where coupling movement between the engagement features of the introducer cannula and syringe results in a secured coupling between the introducer cannula and the syringe. [0013] The system can further include a tagging system configured to determine the unlocked and locked configurations of the syringe and introducer cannula. The tagging system can include a radiotrequency identification (RFID) integrated circuit, wherein the RFID integrated circuit continus alignment of a locking portion of the introducer cannula with a corresponding locking portion of the syringe, where when the RFID integrated circuit detennines that the locking portions of the introducer cannula and syringe are not in alignment, the introducer cannula and syringe are in the unlocked configuration, and when the RFID integrated circuit detennines that the locking portions of the introducer cannula and syringe are in alignment, the introducer cannula and syringe are in the locked configuration. [0014] The delivery tip can include an 18-gauge, 19-gauge, or 20-gauge needle. At least a portion of the delivery tip can be coupled to the proximal end of the introducer cannula and extends at least partially into the central channel of the introducer cannula. [0015] An example system for delivering a crosslinkable biomaterial to a treatment site can include a syringe having a body defining a first volume for containing a first precursor and a separate second volume separate from the first volume for containing a second precursor, a distal end of the hody includes a delivery tip. Thc syringe can also includc a plunger sized and configured to [nove within the first and second volumes of the hody to convey the first and second precursors through the delivery tip. The delivery tip can includc an elongated nccdle defining a first bore and a separate second bore, wherein the first bore is in fluid communication with the first volume of the syringe and the second bore is in fluid communication with the second volume of the syringe, such that the first precursor and the second precursor transmitted through the needle combine as thcy pass through a distal end of the needle. [0016] The system for delivering a crosslinkahlc hiomaterial can also include a barrier separating the first volume from the second volume is opcncd such that contents of the first volume and the second volume combine within the syringe beforc passing through the delivery tip. The system for delivering a crosslinkablc hiomaterial can also include an clongatcd introduccr cannula including a central channel sized and configured to receive the delivery tip therethrough. [0017] An example method of delivering a stimuli-responsive hiomaterial to a treatment site can includc inscrting an introduccr cannula into a hody of a patient, wherein a distal end of the introduccr cannula is located insidc the body of the patient and proxi mate a treatment site and a proximal end of the introducer cannula is located outside the hody of the patient. Thc method can furthcr includc inscrting a delivery tip of a syringe into the proximal end of the introducer cannula, wherein a stimuli-responsive biomaterial is contained within a body of the syringe. The method can further include maintaining the stimuli-responsive biomaterial at a temperature below its liquid-solid phase transition temperature. The method can further include depressing a plunger of the syringe to advance the stimuli-responsive biomaterial in its liquid state through a delivery tip of the syringe and to the treatment site. [0018] The method can further include cooling an interior surface of the body of the syringe to a temperature below the liquid-solid phase transition temperature of the stimuliresponsive biomaterial. The method can further include cooling the introducer cannula using a cooled radiofrequency (RF) probe during a cooled RF ablation procedure. The method can further include cooling the introducer cannula to a temperature below the liquid-solid phase transition temperature of the stimuli-responsive biomaterial using a cooled radiofrequency (RF) probe during a cooled RF ablation procedure. The method can further include moving the introducer cannula and syringe between an unlocked and locked configuration, wherein in the unlocked configuration axial movement of the plunger of the syringe is prohibited, and wherein in the locked configuration axial movement of the plunger of the syringe is permitted. The stimuli-responsive biomaterial can be a thermoresponsive polymer comprising a poloxamer. 6 [00191 Other systems, methods, features and/or advantages will be or may become apparent to one with skill in the art upon examination of the following drawings and detailed description. lt is intended that all such additional systems, methods, features and/or advantages be included within this description and be protected by the accompanying daims Brief Description of Drawings [0020] The components in the drawings are not necessarily to scale relative to each other. Like reference numerals designate corresponding parts throughout the several views. [0021] 1-fie.1A1 is a perspective view of a temperature-controlled system for delivering a thermoresponsive polymer to a treatment site according to implementations described herein. [0022] [fig.1B] is a perspective vicw of an example temperature-controlled system for de- livering a thermoresponsive polymer to a treatment site according to implementations dcscrihed herein. [0023] [fig.2] is a perspective view of the temperature-controlled system of FIG. 1A including a delivery needle. [0024] [fig.3] is a perspective view of the temperature-controlled system of FIG. 1A and an example probe assemhly. [0025] [fig.4] is a perspective view of the example probe of FIG. 3. [0026] [fig.5] is a perspective view of a system for delivering a polymer to a treatment site according to implementations described herein. [0027] [fig.6A] is a perspective vicw of a system for delivering a polymer according to im- plementations described herein. [0028] [Fig. 6B] is a perspective view of a portion of the mixing chambcr of FIG. 6A. [0029] [fig.7] is a top vicw of an example probe positioncd within an intervcrtchral dise of a patient. [0030] [fig.8]is a top view of an example system for delivering a polymer within an inter- vertebral dise of a patient. Description of Embodiments [0031] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. Methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure. As used in the specification, and in the appended claims, the singular forms ' a," an," "the" include plural referents unless the context clearly dictates otherwise. The term "comprising" and variations thereof as used herein is used synonymously with the term -including" and variations thereof and are open, non-limiting terms. The terms optional" or "optionally" used herein mean that the 7 subsequently described feature, °vent or circumstancc may or may not occur, and that the description includes instances where said feature, °vent or circurnstancc occurs and instances whcre it does not. Ranges may be exprcssed herein as from -about" one particular value, and/or to "about" another particular value. Whcn such a range is expressed, an aspect includcs from die one particular value and/or to the other particular value. Similarly, when values arc expressed as approximations, by use of the antecedent -about," it will be undcrstood that the particular value forms another aspect. it will he further undcrstood that the endpoints of cach of the ranges arc significant hoth in relation to the other endpoint, and independently of the other endpoint. As uscd hcrein, the ternis "about" or "approxirnately," when uscd in reference to temperature, mean within plus or minus 10 percentage of the referenced temperature. While impiementations will be dcscrihcd for controlling the temperature of and injecting a biomaterial during an RF ablation procedure and/or cooled RF ablation procedure, it will hccome evidcnt to those skillcd in the art that the implementations arc not limited thercto, but arc applicable for biomatcrials other than stimuli-responsive l'incompatible polymcr, e.g., a thermoresponsive polymers, and crosslinkahlc biornatcrials and/or procédures other than RF ablation. [0032] Rcfcrring now to FIGS. 1 A-8, example temperature-controlled systems arc dcscrihcd. The temperaturc-control system can be uscd for dclivcring a stimuli-responsive biocompatible polymer, such as a thermoresponsive polymer, to a treatment site during an electrosurgical procedure, including, for example, an RF ablation procedure. The temperature-control system may be used with systems used for RF treatment of bodily tissue, in particular, cooled probes including some fonn of temperature and/or impedance monitoring concepts and their corresponding systems, such as those described in U.S. Patent Nos. 6,896,675, 7,163,536, 7,294,127, 7,824,404, 8,043,287, 8,187,268, 8,361,063, 8,518,036, 8,740,897, 8,864,759, 8,882,755, 8,951,249, 9,364,281, 9,468,275, 10,206,739, 10/327,839, the disclosures of which are incorporated herein by reference. [0033] As used herein, a "thermoresponsive polymer," "thennosensitive polymer" or "inverse thermosensitive polymer" is a polymer that exhibits a change in physical property in response to temperature. For example, a thermoresponsive polymer can be in a liquid state at a relatively low temperature (e.g., when cooled or refrigerated) but in a gel and/or solid state at a relatively high temperature (e.g., at room temperature or body temperature). In other words, a thennoresponsive polymer can change phase in dependence on temperature. As described in more detail below, the syringe 100 can maintain a thermoresponsive polymer at a temperature below its liquid-solid phase transition temperature such that the thermoresponsive polymer is in a liquid state within the syringe 100 and prior to delivery to the treatment site. A "poloxamer" is an 8 cxamplc thermoresponsive polymcr. Poloxamers can be used for drug del ivcry as well as crcating a physical harricr between the target nervc and the surrounding tissue. Although poloxamers arc described in the cxamplcs herein, this disclosurc contemplates that the thermoresponsive polymcr is not limitcd to poloxamers. [0034] In some embodiments, the inverse thermosensitive polymer can exhibit a transition temperature of from 10°C to 37°C. In somc cases, the inverse thermosensitivc polymcr can be a liquid at 4°C, and undergoes a transition from a liquid to a gel or solid upon an incrcasc in temperature from 4°C to 37°C. In somc cases, the inverse thermosensitive polymcr can be a liquid at 23°C, and undergoes a transition from a liquid to a gel or solid upon an incrcase in temperature from 23°C to 37°C. [0035] A numbcr of suitahle inverse thermosensitive polymers arc known in the art, and suitahle for use in conjunction with the methods dcscrihcd hercin. In somc cxamplcs, the inverse thermosensitivc polymer can comprise a poly(alkylene oxidc), such as a poly(alkylene oxidc) block copolymcr. In certain cxamplcs, the inverse thermosensitive polymcr comprises a poloxamcr, a poloxaminc, or a comhination thereof. For cxamplc, the inverse thermosensitive polymer can comprise poloxamer 407, poloxamer 188, poloxamcr 234, poloxamcr 237, poloxamcr 338, poloxaminc 1107, poloxaminc 1307, or a comhination thcrcof. In some embodiments, the inverse thermosensitive polymcr can comprise poloxamer 407, poloxamcr 188, or a comhination thercof. [0036] In certain embodiments, the inverse thermosensitive polymer can comprise (i) from 20% to 40% by weight of a first inverse thermosensitive polymer defined by Formula I below: [Chem.1] Formula I wherein a is an integer from 90 to 110 and b is an integer from 50 to 60, wherein the first inverse thermosensitive polymer has a molecular weight of from 9,500 Da to 15,000 Da, and wherein the first inverse thermosensitive polymer has a polyoxyethylene content of from 70% to 75%; and (ii) from 5% to 50% by weight of a second inverse thermosensitive polymer defined by Formula I below: [Chem.2] Formula I 9 wherein a is an integcr from 70 to 90 and h is an integer from 20 to 35, wherein the first inverse thermosensitive polymer has a molecular weight of from 7,500 Da to 10,000 Da, and wherein the first inverse thermosensitive polymer has a polyoxyethylene content of from 78% to 85%. [0037] The system can include a syringe 100 including a body 102 defining a volume containing a biomatcrial, c.g., a thermoresponsive polymer. The biomaterial can be introduced into the patient hefore, during, and/or after the RF ablation procedure. For example, the biomaterial can be introduced at the treatment site hefore and/or during the ablation procedure to insulate various tissue structures and/or help conduct and direct the clectrical signal at select target tissue. In another example, the biomatcrial can he delivered to the treatment site hefore and/or during the ahlation procedure to create a physical barrier between the targct nerve and the surrounding tissue. In another example, the biomaterial can he introduced at the treatment site during/simultaneous with the RF ahlation procedure to facilitatc cooling of the treatrnent site. In anothcr example, the biomaterial can he introduced at the treatment site hefore, during, and/or after the ablation procedure for drug delivery to the target ncrvous structure and/or surrounding tissue. Likewise, the biomaterial can be introduced at the treatment site hefore, during, and/or after the ablation procedure to facilitatc additional and/or continucd modulation of the targct nervous structure. [0038] The biomaterial can he contained in the volume defined by the space between a scal 112 and a delivery tip 130 of the syringe 100. The proximal and distal ends of the syringe 100 are labeled 101A and 101B, respectively, in FIGS. 1A and 1B. As used herein, the terris "distal and "proximal' are defined with respect to the user and when the device is in use. That is, the terra "distal refers to the part or portion further away from the user, while the terni "proximal" refers to the part or portion doser to the user, when the device is in use. The syringe 100 can include the delivery tip 130 at the distal end 101B with an opening providing fluid communication from the volume of the body 102. The system can also include a plunger 104 sized and configured to move axially within the volume of the body 102. The axial direction is labeled by dashed line 160 in FIGS. 1A and 1B. When the plunger 104 moves axially within the body 102, the biomaterial liquid can be conveyed through the opening of the delivery tip 130. For example, as the plunger 104 is translated in the axial direction, the biomaterial liquid is pushed by the seal 112 and exits the syringe 100 through the opening of the delivery tip 130. The body 102 and the plunger 104 can include [langes 110 and 108, respectively, which assist a user operating the syringe 100. [0039] Referring again to FIGS. 1A-2, the syringe 100 can maintain a biomaterial comprising a thermoresponsive polymer liquid, e.g., a poloxamer, at a temperature below its liquid-solid phase transition temperature. As described above, the thermore- sponsive polymer can change state in dependence on temperature. Accordingly, in sonie implcmentations, the syringe 100 can be configurcd to keep the thermoresponsive polymer cool such that it is maintained in a liquid state within the syringc 100 prior to delivery to the treatment site. During a medical proccdure such as RF ablation, the thermoresponsive polymcr such as a poloxamer used for drug delivery can be dispensed from the syringe 100 to the treatment site as a liquid where it then transitions phase as the temperature of the polymer changes. It should be undcrstood that the liquid-solid phase transition temperature is a charactcristic of the material, and the syringe 100, needle/cannula 132 and/or introduccr 200 can be configurcd to maintain the thermoresponsive polymcr at the desired temperature to prevent solidification of the biomaterial before it rcaches the treatment site. The phase transition temperature can range, for example, between about 5°C and 45°C for different materials. [0040] The body 102 of the syringc 100 can includc a cooling mechanism 150 for maintaining an interior surface of the body 102 at a temperature helow the liquid-solid phase transition temperature of the thermoresponsive polymer liquid. As provided in FIGS. 1 A and 1B, the cooling mcchanism 150 can include a sleeve-like structure that extends circumferentially around the perimeter of the body 102 of the syringe 100 and along a length of the body 102. For example, the sleeve-like structure of the cooling mechanism 150 can be applicd over the distal end of the syringe 100 such that the delivery tip 130 cxtends through an opening at the distal end of the cooling mechanism 150. The body 102 of the syringe 100 may then slide within the elongated annular opening defined by the body of the cooling mechanism 150 to a desired position, where the location of the body 102 with respect to the cooling mechanism 150 is fixed. As illustrated in FIG. 1A, the cooling mechanism 150 defines a sleeve-like structure, wrapping circumferentially around the body 102 of the syringe 100, and covering a portion of the overall length of the body 102, without covering the distal end of the syringe 100. In another example (not shown), the cooling mechanism 150 defines a sleeve-like structure that wrapping circumferentially around the body 102 of the syringe 100 and extends along the entire length of the body 102, without covering the distal end of the syringe 100. In a further example, illustrated in FIG. 1B, the cooling mechanism 150 defines a sleeve-like structure that wraps circumferentially around the body 102 and extends along the entire length of the body 102 of the syringe 100. As provided in FIG. 1B, the distal end of the cooling element 150 extends over at least a portion of the distal end of the body adjacent the delivery tip 130. [0041] The cooling mechanism 150 may include a window 152 to provide visual access by the user to the body 102 and the contents of the plunger 100. For example, the window 152 allows the user to visually inspect the liquid and/or solid state of the polymer contained therein, the location of the plunger 104 within the body 102, and/or 11 any markings on the exterior of the body 102. Tt is also contemplatcd that the cooling mcchanism 150 will not includc a window 152, but rathcr daine an unintcrrupted structure cxtcnding circumfercntially around the entire circurnference of the body 102. [0042] The cooling mcchanism 150 can he integrally formcd with the body 102 of the syringc 100. Thc cooling mcchanism 150 can lie removably and/or fixcdly couplcd to the syringc 100 in a position to cool the thermoresponsive polymer liquid containcd therein. The cooling mechanism 150 can be removably and/or fixcdly coupled to the body 102 of the syringc 100 hy a mcchanical and/or chemical fastener (e.g., adhesive). Various mcchanical fasteners includc, for example, recess or dotent and corresponding projection providcd between the cooling mcchanism 150 and the syringe 100, tapered surface for providing a press fit between the cooling mcchanism 150 and the syringc 100, clip, thrcad, hayonet mount, weld, or any other mcchanical fastener. Likewise, the cooling mcchanism 150 can he formcd around the body 102 such that removal of the cooling mcchanism 150 is not possible without damaging the cooling mcchanism 150 and/or the syringe 100. [0043] The cooling mcchanism 150 can includc an insulativc material providcd around the body 102 of the syringc 100. The insulativc material can optionally he attached to one or more portions or arcas on the exterior of the body 102 of the syringc 100. Thc insulativc material can optionally he a thin insulating material such as THINSULATE from 3M Company of Maplewood, Minnesota. Alternatively or additionally, the cooling mechanism 150 and/or body 102 of the syringe 100 can be formed from a double wall vacuum insulated material. Alternatively or additionally, the cooling mechanism 150 can be used to provide active cooling to the syringe 100 and the thermoresponsive polymer. For example, the cooling element 150 can include a cooling pad coupled or attached to the exterior of the body 102 of the syringe 100. For example, the cooling pad component can include, for example, an "instant cold" pad (e.g., water and ammonium nitrate solution the combination of which results in an endothermic reaction causing the cooling pad to rapidly chill) and/or reusable gel cold pad. As described above, the cooling mechanism 150 can be removably coupled to the body 102 of the syringe 100. Similarly, the cooling pad component can be separable from the cooling mechanism 150. For example, the cooling pad component can be replaced in the case of an "instant cold" pad type cooling pad, or the reusable gel cold pad can be chilled for later use. [0044] Altematively or additionally, the cooling mechanism 150 can include a thermo- electric cooler such as a Peltier cooler. Thennoelectric coolers are known in the art and are therefore not described in further detail herein. Altematively or additionally, in some implementations, the cooling mechanism 150 can include a chilled water system. The chilled water system can be configured to flow water around the body 102 of the 12 syringe 100. Optionally, the chillcd water can he treated with ozone, which can improvc hcat transfer capability of the cooling mechanism 150. [0045] The cooling mcchanism 150 can he used to maintain an interior surface of the body 102 of the syringc 100 at a temperature helow about body temperature (c.g., between about 28°C and about 32°C external body temperature or between about 35°C and about 42°C internai body temperature). In some implemcntations, an interior surface of the body 102 of the syringc 100 can be maintaincd at a temperature helow about room temperature (e.g., the temperature of a hospital/operating room between about 19°C and about 25°C). In some implémentations, the syringc 100 and/or the thermoresponsive polymer can be maintaincd a temperature below about 20°C. In some impiemcntations, the syringc 100 and/or the thermoresponsive polyrner can be maintaincd at a temperature at or bclow about 4°C. It should he understood that the temperature ranges providcd above arc providcd only as examples. This disclosure contemplates maintaining the syringc 100 and/or thermoresponsive polymer at temperatures other than thosc providcd as examples. As described herein, the syringc 100 can he configured to maintain the thermoresponsive polymer at the material-dependent temperature that prevents solidification. [0046] The cooling mcchanism 150 may includc one or more temperature sensors along its length for mcasuring the temperature of the thermoresponsive polymer contained within the syringc 100. The cooling mcchanism 150 may also includc a temperature indicator for providing information to the user regarding the temperature of the thermoresponsive polymer. The temperature indicator may extend along the length of the cooling mechanism 150 and identify the conesponding temperature of the syringe 100 and/or thermoresponsive polymer at that location. For example, the temperature indicator may identify temperatures along the length of the cooling mechanism 150 so that the user is able to determine if any portion of the thermoresponsive polymer is at a temperature above the phase transition temperature and thereby solidifying within the body 102 of the syringe 100. This is particularly relevant to help the user identify if the thermoresponsive polymer has solidified in the (listai portion of the body 102 and is preventing or inhibiting the flow of the polymer through the delivery tip 130. [0047] Referring now to FIG. 3, the system can optionally include an elongated introducer cannula 200. In some implementations, RF ablation can be perfonned on a patient via a catheter, and the introducer cannula 200 can serve as the catheter through which RF ablation is perfonned, for example, by coupling a cooled RF probe 300 to and/or passing through the introducer cannula 200 to the treatment site. The introducer cannula 200 is used to provide access to the treatment site within the patient's body. The introducer cannula 200 can define proximal and distal ends and a central channell bore extending therebetween. In use, the proximal end of the introducer cannula 200 is 13 located outsidc of the patient's body and the distal cnd of the introduccr cannula 200 is located insidc the patient' s body adjacent the treatment site. The central channel is sized and configurcd to receive the delivery tip 130 of the syringe 100 therethrough. The introduccr cannula 200 can includc a single port for acccssing the central channel, alternative, the introduccr cannula 200 can includc separate ports for each of the syringe 100/delivery tip 130/ncedle 132 and the RF probe 300. As described in more detail helow, the elongate shaft 310 of a probe assemhly 300 may he introduccd to the treatment site through the longitudinal bore of the introduccr cannula 200. The introduccr cannula 200 may further comprise one or more depth markers in order to enable a user to determine the depth of the distal cnd of the introducer cannula 200 within a patient's body. Additionally, the introduccr cannula 200 may comprise one or more radiopaque markers to ensure the correct placement of the introduccr cannula 200 when using fluoroscopic guidance. The introduccr cannula 200 may comprise one or more temperature sensors along its length. In such cmhodiments, the one or more temperature sensors may he placed proximate to the distal end of the introduccr cannula 200 so as to enable the one or more temperature sensors to measure the temperature of tissue surrounding the distal end of the introduccr cannula 200. The introduccr cannula 200 may includc multiple temperature sensing elements disposed along the introduccr cannula 200 may he used to indicate the sizc of the lesion as it expands. This may he particularly useful in the treatment of tumor tissue, for example. The introducer cannula 200 may include temperature sensing elements disposed along its central channel for measuring a temperature of the syringe 100, cooling mechanism 150, and/or probe 300. Introducer cannulas 200 may be made of various materials, as is known in the art and, if said material is electrically conductive, the introducer tubes may be electrically insulated along all or part of their length, in order to prevent energy from being conducted to undesirable locations within a patient's body. [0048] Optionally, a second cooling mechanism 250 can be provided to reduce the tem- perature of the introducer cannula 200. It is contemplated that the second cooling mechanism 250 can be similar to the cooling mechanism 150 as described above. For example, the second cooling mechanism 250 of the introducer cannula 200 can include at least one of an insulative material provided around the introducer cannula 200, a double wall vacuum insulated material, a cooling pad coupled to the introducer cannula 200, a theimoelectric cooler, or a chilled water system for flowing a volume of chilled water around the introducer cannula 200. [0049] As illustrated in FIG. 2, the delivery tip 130 of the syringe 100 can include a needle/ cannula 132 for transmitting the biomaterial liquid from the body 102 of the syringe 100, through the introducer cannula 200, and to the treatment site. For example, needle/cannula 132 can include an 18-gauge, 19-gauge, or 20-gauge needle. The in- 14 troduccr cannula 200 into which the dclivcry tip 130 and needle/cannula 132 is inscrted can have a 17-gauge opening. It should hc undcrstood that the sizes of the needle and/or introduccr cannula described abovc arc provided only as examples. This disclosure contemplates using a needle and/or introduccr cannula having sizes othcr than thosc provided as examplcs. The needle/cannula 132 can be flexible or rigid. The needle/cannula 132 can cxtend at least partially into a central channel of the introducer cannula 200. In one example, the needlc/cannula 132 extends only partially into the central channel of the introduccr cannula 200 such that the biomaterial liquid passes through the central channel of the introduccr cannula 200 to the treatment site. In another example, the needlc/cannula 132 extends to the distal end of the introducer 200 and/or bcyond the distal end of the introduccr 200 such that the liquid biomaterial passes directly from the distal end of the needlc/cannula 132 to the treatment site. [0050] The introduccr cannula 200 is operahle to casily and securely couple with probe assemhly 300 and/or syringc 100. For example, the proximal end of the introducer cannula 200 at the introduccr huh 206 may he fitted with a connector able to mate reversihly with the huh 324 of probe assemhly 300 and/or the delivery tip 130 of the syringc 100. In an example system, the connector betwcen the introduccr cannula 200 probe assemhly 300 and/or syringe 100 comprises a Luer fitting. Luer fittings arc standardized (c.g., International Organization for Standardization (ISO)) fluid connection fittings known in the art and arc therefore not dcscribcd in further detail herein. It is desirable to couple the delivery tip 130 to the proximal end of the introducer cannula 200, for example, when the needle/cannula 132 extends only partially into the introducer cannula 100. A liquid-tight coupling between the delivery tip 130 and the proximal end of the introducer cannula 200 ensures that none of the liquid biomaterial escapes from the proximal end of the introducer cannula 200. Likewise, in an example syringe 100 not including a needle/cannula 132, a liquid-tight coupling between the delivery tip 130 and the introducer cannula 200 allows the introducer cannula 200 to provide fluid communication of the liquid biomaterial between the syringe 100 body 102 and the treatment site while ensuring that none of the liquid biomaterial escapes from the proximal end of the introducer cannula 200. [0051] In an example system, the connector between the introducer cannula 200 and the syringe 100 includes an engagement/locking feature that limits and/or prohibits movement of the plunger 104 and the resulting dispensing of the biomaterial. For example, the connector can include a locking feature is provided at the proximal end of the introducer cannula 200 and couples with a corresponding engagement feature 106 provided at the distal end of the syringe 100. Engagement between the engagement/ locking feature in the hub 206 of the introducer cannula 200 and the engagement features 106 of the syringe 100 can be used to limit and/or prohibit movement of the plunger 104 and the resulting dispcnsing of the biomaterial. The engagement/locking feature is movablc between unlocked and locked configurations. As used hercin, when in the unlocked configuration, engagement fcaturc 106 and the corresponding engagement/locking feature in the huh 206 arc not couplcd. In the unlockcd configuration, axial movement of the plungcr 104 within the volume of the body 102 is prohihited. On the other hand, when in the locked configuration, the engagement feature 106 and the corresponding engagement/locking feature in the huh 206 arc couplcd, and axial movement of the plunger 104 within the volume is permitted. Optionally, the engagement fcaturc 106 and corresponding engagement feature in the huh 206 can be male and female Lucr fittings providcd at the distal end of the syringc 100 and the proximal end of the introducer cannula 200, respectively. Rotational movement between the male and female Lucr fittings results in secured coupling between the introducer cannula 200 and the syringc 100. It should he understood that Luer fittings arc providcd only as examples of engagement features. This disclosure contemplates that the engagement feature 106 and corresponding engagement feature in the huh 206 can be fittings other than Luer fittings. For example, the engagement feature 106 and corresponding engagement fcaturc in the huh 206can optionally include at least one of a recess or dotent provided in one of the delivery tip 130 or huh 206 and a corresponding a projection provided in the opposing structure, clip, thrcad, hayonet mount, or any other mcchanical fastener/coupling capable for providing a secure and generally leakproof coupling and locking feature between the syringe 100 and the introducer cannula 200. This disclosure contemplates that feature 106 and corresponding engagement feature in the hub 206 can be configured to couple and allow for relative movement between the locked and unlocked configurations. It should be understood that the design of the engagement feature 106 and corresponding engagement feature in the hub 206 should not be limited by the examples provided above. [0052] Optionally, and as shown in FIGS. 1A and 1B, the system can include a plunger restraint mechanism 120 coupled to the plunger 104. The restraint mechanism 120 can be configured to restrict (e.g., physically restrict) axial movement of the plunger 104 and delivery of the thennoresponsive polymer. The restraint mechanism 120 can be removed by a user to permit axial movement of the plunger 104 within the body 102 of the syringe 100. As illustrated in Ras. lA and 1B, the restraint mechanism 120 is in the foret of an elongated c-shaped clip that is received over the stem portion of the plunger 104 between flange 108 of the plunger 104 and flange 110 of the body 102. Opposing sicles of the restraint mechanism 120 can be tlexed to increase the gap therebetween and remove the restraint mechanism 120 from the plunger 104 stem. As illustrated in FIGS. lA and 1B, the length of the plunger restraint mechanism 120 corresponds to the location of the seal 112 within the body 102, where the location of the 16 scal 112 is determinative of the volume of the biomaterial includcd in the body 102. It is contemplated that different lengths of restraint mechanisms 120 can he providcd to accommodats different scal 112 locations, i.c., different volumes of biomaterial. In another example (not shown), the plunger restraint mechanism 120 is in the form of a break-away/tear-away tab or harrier that restricts axial movement of the plungcr 104. [0053] As providcd above, the temperature-controlled syringc 100 described hercin rnay he used with systems providing RF treatment of hodily tissue, in particular, cooled probes including some forrn of temperature and/or itnpedance monitoring. An example probe 300 is providcd in FIGS. 3 and 4. The probe 300 includes an clongate member, comprising an clongated shaft 310, a distal tip rcgion 312 comprising one or more energy del ivcry devices, a distal end 314, a proximal rcgion 316, and a proximal end 318. With reference to FIG. 3, an embodiment of a system suitable for use with probe 300 may comprise one or more of: one or more introduccr cannula 200; one or more dispersive rcturn clectrodes (not shown); one or more sources of cooling, for example pump 340; one or more energy sources, for example generator 350 and one or more connecting means, for example tube 342 and/or sable 352 [0054] Probe 300 comprises an clectrically insulated portion 320 and an clectrically exposed conductivc portion 322. Elcctrically exposed conductivc portion 322 may also he referred to as an active clectrode and is an example of an "energy del ivcry portion" of the probe 300. The proximal rcgion 316 of probe 300 comprises a hub 324. Hub 324 is structured to operatively connect other devices, such as connecter cables, cannulae, tubes, or other hubs, for example, to probe 300. For example, probe 300 may be coupled to an energy source and/or to a source of cooling via respective connecting means (for example, an electrical cable and/or flexible tubing) which may be associated with hub 324. Hub 324 may also serve as a handle or grip for probe 300. Hub 324 may be manufactured from a number of different materials, including, but not limited to, plastics, polymers, metals, or combinations thereof. Furthermore, hub 324 may be attached to probe 300 by a number of different means. For example, in one embodiment, hub 324 may be made from polypropylene, and may be attached to probe 300 by insert molding. [0055] The size of probe 300 may vary, depending upon which of the method embodiments, described herein below, are used. In some examples, the length from distal end 314 to proximal end 318 of probe 300 may be between about 5 cm and about 40 cm and the outer diameter of shaft 310 may be between about 0.65 mm and about 2.00 mm (between about 20 G and about 12 G). In one specific example, the length of the probe may be about 7.5 cm and the outer diameter may be about 1.5 mm Furthernlore, the size and chape of active electrode 322 may vary, as is further described in U.S. Patent Application Ser. No. 11/457,697 (issued as U.S. Patent No. 10/206,739), previously in- 17 corporated herein hy reference. For example, in some embodiments, active clectrode 322 may be between about 2 mm and about 8 mm in lcngth. In other embodiments, active electrode 322 may comprise suhstantially only the distal face of probe 300. [0056] In some embodiments, clectrically insulatcd portion 320 may be formed hy coating a portion of shaft 310 with an electrically insulativc coating, covering, or shcathing. For example, in one particular embodiment, shaft 310 of probe 300 may be fahricatcd from a l'incompatible [notai or alloy, for example stainlcss steel, which may be overlaid in part hy an insulating coating, for example polytetrafluoroethylene (PTFE). In other embodiments, shaft 310 may be fahricated from another metal, such as nitinol or titanium, and/or die insulating coating may comprise a different clectrically insulating matcrial, including but not limited to polyethylene terephthalate (PET). In other embodiments, other tais or electrically insulating matcrials may be used. [0057] The probe 300 is structurcd such that it may be coolcd hy the internai circulation of a cooling fluid. Such a configuration, whereby a cooling medium does not exit from a distal region 312 of probe 300, may be referred to as an internally-cooled probe. The cooling fluid may lie any fluid suitablc for removing hcat from probe 300 during surgcry, for example water. Other exampies of cooling fluid include, but arc not limited to, liquid nitrogcn and saline. Furthermore, the fluid may be at any temperature suitable for removing hcat from the probe during surgcry, for example between about 0° C. and about 25° C. More spccifically, the temperature of the fluid may be at about room temperature (21° C.), about 4° C., or about 0° C., depending on the application. [0058] The fluid may be delivered or circulated at a wide range of flow-rates. An ap- propriate flow-rate may be deteimined or calculated based on a number of factors, including the conductivity and heat capacity of probe 300, the cooling fluid and/or the tissue, and the desired temperature of (lista]. end 314 of probe 300, among other factors. In some embodiments, the fluid may be delivered at between about 10 ml/min and about 30 ml/min. [0059] As mentioned hereinabove, one or more fluids may be delivered from a reservoir to the probe 300 for the purposes of cooling the probe 300. The fluid(s) may be delivered to the probe 300 via a number of means, and the invention is not limited in this regard. For example, in one embodiment and with reference to FIG. 3, the reservoir of fluid may comprise a container, for example an intravenous (IV) bag 330, which is elevated above the patient. Tubing 332, for example clear plastic flexible tubing, may be used to connect the reservoir to an inlet in probe 300. A valve 334 may be placed at the junction of the container and the tubing (or at some other location between the container and the probe), such that when the valve 334 is opened, gravity may cause fluid to flow towards probe 300. After circulation within probe 300, fluid may exit probe 300 via tubing, which may drain into another reservoir, for example a second IV 18 hag, or into a sink or other drain. In anothcr embodiment, at least one pump may he uscd to deliver fluid to the probe 300. [0060] The probe 300 can also includc a peristaltic pump 340 operatively connected to a reservoir of fluid and configured to circulate the chilled fluid (e.g., deionized (DI) water). The reservoir of fluid may he an IV hag, a polypropylene vial or burette, or anothcr container, for example. The pump 340 may pump the fluid from the reservoir to an inlet in probe 300. After circulating in probe 300, the fluid may exit the probe through an outlet in probe 300 and may flow through a tube to cuber the sanie or a different reservoir or, alternatively, to an alternat° location as described ahove. A hcat sink, hcat exchanger, or other cooling source such as a refrigerant chiller may he uscd to cool the fluid Act exiting the probe 300. A second pump, gravity, or a source of suction, for example, may assist in drawing the fluid out of the probe 300. The use of other types of pumps to supply a cooling fluid to and return a cooling fluid from the probe 300 is contemplated including, for example, a centrifuga] pump or a piston pump. Further details regarding the cooling source arc provided in U.S. patent application Ser. No. 11/105,527 (filed on Apr. 14, 2005) and Ser. No. 10/864,410 (filcd on Dec. 10, 2005). [0061] By leaving the probe 300 coupled to the introducer cannula 200 and running the pump 340 hefore delivering the thermoresponsive polymer within the syringe 100 via the cannula 200, the probe 300 can bc uscd to pre-cool the introducer cannula 200 and/ or treatment site by circulating chilled liquid through the probe 300. In some impiementations, the probe 300 can be used to maintain the introducer cannula 200 at a temperature below the liquid-solid phase transition temperature of the thermoresponsive polymer. [0062] Probe 300 is structured to be operatively connected to an energy source, for example a generator 350. The connecting means for connecting probe 100 to generator 350 may comprise any composent, device, or apparatus operable to make one or more electrical connections, for example an insulated wire or cable. In one embodiment, the connecting means comprises an electrical cable 352 terminating at hub 324 as well as a connector at a proximal end thereof. Cable 352 may be operable to couple to energy source 350 directly or indirectly, for example via an intermediate cable. At least one wire or other electrical conductor associated with cable 352 may be coupled to conductive portion of shaft 310, for example by a crimp or solder connection, in order to supply energy from energy source 350 to shaft 310. In one specific embodiment, a 4-pin medical connector is used to connect cable 352 to an intermediate cable (not shown), which may be further attached to a 14-pin connector capable of being automatically identified when connected to generator 350. Further details regarding such an embodiment are disclosed in U.S. patent application Ser. No. 10/122,413 (filed on Apr. 19 16, 2002), incorporatcd hcrein hy reference. [0063] Gencrator 350 may producc various types of encrgy, for example microwave or radio-frequency clectrical energy. In some emhodiments, generator 350 produces radiofrcquency clectrical current, having a frcquency of betwecn about 10 kHz and about 1000 kHz, at a power of hetween about 1 W and about 50 W. An example of an RF generator that may he used as part of a system of the prcscnt invention is the Pain Management Gencrator (PMG) of Baylis Medical Company Inc. (Montreal, QC, Canada). Further details regarding embodi monts of cnergy sources arc disclosed in U.S. Patent Application Ser. No. 11/457,697 (issued as U.S. Patent No. 10/206,739), previously incorporatcd hcrein hy reference. [0064] As illustrated in FIGS. 3 and 4, the temperature-controlled syringe 100 and probe 300 described hcrein when used in conjunction with one or more introducer cannulas 200, may further comprise one or more stylets 400. The stylet 400 may have a heveled tip to facilitate insertion of the introducer cannula 200 into a patient' s body. Various forms of stylets 400 arc well known in the art and the prcsent invention is not limited to include only one spccific form. [0065] Optionally, thc system can include a motor. The motor can he operahly couplcd to the syringe 100 and/or the cooling unit 150/250. The motor can he configured to control the flow of the biomatcrial from thc syringe 100 and/or thc flow of cooling fluid in the cooling unit 150/250. [0066] The system can optionally include a tagging system. In some implementations, the tagging system includes an electronically scannable code including, but not limited to, a bar code or QR code. For example, the electronically scannable code can be provided on the body 102 of the syringe 100 such that the electronically scannable code can be read by the system prior to delivering the biomaterial. The electronically scannable code can encode information including, but not limited to, the temperature at which to maintain the biomaterial and/or the flow rate. Such information can be used by the system for controlling the motor, cooling unit 150/250, and/or cooled RF probe 300. Alternatively or additionally, in some implementations, the system can optionally include a tagging system configured to determine the unlocked and locked configurations of the syringe 100 and introducer cannula 200. For example, the tagging system can include a radioti-equency identification (RFID) integrated circuit. The RFID integrated circuit can be provided on portions of the engagement features 106, 206 described above. For example, each of the introducer cannula 200 and the syringe 100 can include a respective locking portion. Optionally, the corresponding locking portions can be provided on the corresponding engagement features 106, 206 described above. The RFID Integrated circuit can confirm alignment of a locking portion of the introducer cannula 200 with a corresponding locking portion of the syringe 100. When the RFID intcgratcd circuit &termines that thc locking portions of the introduccr cannula and syringc arc not in alignmcnt, the introduccr cannula 200 and syringc 100 arc in the unlockcd configuration. As dcscrihcd abovc, the syringc and introduccr cannula engagement fcatures 106,206 arc not couplcd in the unlockcd configuration and axial movcmcnt of the plungcr 104 is prohibitcd. Whcn the RFID intcgratcd circuit dctcrmincs that the locking portions of the introduccr cannula and syringc arc in alignmcnt, the introduccr cannula 200 and syringc 100 arc in the lockcd configuration. As dcscrihcd above, the syringc and introduccr cannula engagement fcaturcs 106,206 arc couplcd in the lockcd configuration and axial movcmcnt of the plungcr 104 is permittcd. Optionally, the RFID intcgratcd circuit can providc information to thc systcm, and such information can hc uscd for controlling the motet- and/or cooling unit 150/250. In somc implcmcntations, such information can hc uscd to control lights or othcr indicators providcd hy the system to facilitatc manual or automatic control. It should hc undcrstood that the tagging systems dcscrihcd ahovc arc providcd only as cxamplcs. This disclosurc contemplates using tagging systems othcr than cicctronically scannahlc codes and/or RFID intcgratcd circuits. [0067] As illustratcd in FIGS. 5-6B, in some implcmcntations, the syringc 100 can have a double harrcl configuration. A double harrcl configuration can hc uscd to combine or mix a crosslinkahlc biomaterial at the treatment site. As dcscrihcd in more dctail below, the crosslinkahlc hiomatcrial can be formcd from a first precursor and a second precursor which react in situ to form a polymeric matrix. Accordingly, the first precursor and the second precursor must be separately stored prior to being combined at the treatment site. As provided in FIGS. 5-6B, the body 102 of the double barrel syringe 100 can define a second volume 102a separate from the main volume 102b and conesponding plungers first plunger 104a and a second plunger 104b. The main volume 102a can be configured to contain a first precursor and the second volume 102b can be configured to contain a second precursor. Optionally, the syringe 100 may include a cooling mechanism 150 for maintaining the first and second precursors at a desired temperature. Illustrated in FIG. 5, the delivery tip 130 can include an elongated needle 132 defining a first bore 132a and a separate second bore 132b, where the first bore 132a is in fluid communication with the main volume 102a of the syringe 100 and the second bore 132b is in fluid communication with the second volume 102b of the syringe 100. Accordingly, a first precursor and a second precursor transmitted through the needle 132 first contact/combine as they pals through a distal end of the needle 132. Alternatively, as illustratcd in FIG. 6A, the delivery tip 130 and/or needle/cannula 132 can include a mixing chamber wherein the first precursor and the second precursor combine before exiting the needle/cannula 132 and/or introducer cannula 200. The mixing chamber can be positioned at any suitable point along the length of the delivery 21 tip 130 and/or needle/cannula 132. In some examples, the mixing chamber is positioncd entirely within the delivery tip 130, such that the first and second precursors arc combined before entering the needle/cannula 132. In anothcr example, the mixing chamber is positioncd within the distal region of the needlc/cannula 132. In a further example, as illustrated in FIG. 6A, the mixing chamber is positioned along a majority of the length of the needle/cannula 132. [0068] The mixing chamber can includc one or more fluid channels configurcd to mix two solutions flowing into the mixing channel from the first body 102a and the second body 102h. The mixing chamber can adopta varicty of geometries, hased on for example the solutions to he mixed and the length of the mixing chamber. For example, the mixing chamber can he configured to mix (e.g., to render homogencous) two solutions which flow through the mixer. The mixing chamber can he, for example, a channel (e.g., a serpentine or tortuous channel, or a channel containing one or more protrusions) which induces turbulent flow so as to mix the fluids. As illustrated in FIG. 6A and 6B, the mixing chamber can includc a hclical mixing path, the mixing path is defined hy helixes that forrn 180° turns within the central lumen of the needle/cannula 132. Each turn mixes the two precures about 50%, such that a homogenous mixture exits the needle/cannula 132 and is introduccd at the treatment site. In anothcr example (net shown), a barder separating the main volume from the second volume can he opened such that contents of the main volume and the second volume combine within the syringe 100 before passing through the delivery tip 130. [0069] Suitable precursor molecules can be selected in view of the desired properties of the crosslinkable biomaterial and resultant polymeric matrix. In some cases, the crosslinkable biomaterial comprises one or more oligomeric or polymeric precursor molecules. For example, precursor molecules can include, but are not limited to, polyether derivatives, such as poly(alkylene oxide)s or derivatives thereof, polysaccharides, peptides, and polypeptides, poly(vinyl pyrrolidinone) ("PVP"), poly(amino acids), and copolymers thereof. [0070] The precursor molecules can further comprise one or more reactive groups. Reactive groups are chemical moieties in a precursor molecule which are reactive with a moiety (such as a reactive group) present in another precursor molecule to fonn one or more covalent and/or non-covalent bonds. Examples of suitable reactive groups include, but are not lirnited to, active esters, active carbonates, aldehydes, isocyanates, isothiocyanates, epoxides, alcohols, amines, thiols, maleimides, groups containing one or more unsaturaturated C-C bonds (e.g., alkynes, vinyl groups, vinylsulfones, acryl groups, methacryl groups, etc.), azides, hydrazides, dithiopyridines, N-succinimidyl, and iodoacetamides. Suitable reactive groups can be incorporated in precursor molecules to provide for crosslinking of the precursor molecules. [0071] -In some embodiments, one or more of the prccursor molecules comprises a poly(alkylcnc oxidc)-hascd oligorner or polymer. Poly(alkylcnc oxidc)-based oligorner and polymcrs arc known in the art, and includc polycthylcnc glycol ("PEG"), polypropylcnc oxidc ("PPO"), polycthylcnc oxide-co-polypropylene oxidc ("PEO-PPO"), co-polycthylcnc oxidc block or random copolymcrs, poloxamers, mcroxapols, poloxamincs, and polyvinyl alcohol ("PVA"). Block copolymcrs or homopolymers (when A=B) may hc lincar (AB, ABA, ABABA or ABCBA type), star (A 'B or BA'C, whcrc B is at lcast n-valent, and n is an integer of from 3 to 6) or hranchcd (multiple A's depending from one B). In certain embodiments, the poly(alkylene oxide)-hased oligomer or polymcr comprises PEG, a PEO-PPO block copolymcr, or comhinations thereof. -In some embodiments, one or more of the prccursor molecules is defined hy Formula 1 or Formula 11: [Chcm.3] lula 1 ail whercin: W is a hranch point; A is a rcactivc group (e.g., a nucicophilic group or a conjugatcd unsaturatcd group); m and n arc integcrs of from 1 to 500 (e.g., an intcgers of from 1 to 200); and j is an integer greater (han 2 (e.g., an integer of from 2 to 8). [0072] -In some embodiments, one or more of the prccursor molecules comprises a biomacromolecule. The biomacromolecule can be, for example, a protein (e.g., collagen) or a polysaccharide. Examples of suitable polysaccharides include cellulose and derivatives thereof, dextran and derivatives thereof, hyaluronic acid and derivatives thereof, chitosan and derivatives thereof, alginates and derivatives thereof, and starch or derivatives thereof. Polysaccharides can derivatized by methods known in art. For example, the polysaccharide backbone can be modified to influence polysaccharide solubility, hydrophobicity/hydrophilicity, and the properties of the resultant polymeric matrix formed from the polysaccharide (e.g., matrix degradation time). In certain embodiments, one or more of the precursor molecules comprises a biomacromolecule (e.g., a polysaccharide) which is substituted by two or more (e.g., from about 2 to about 100, from about 2 to about 25, or from about 2 to about 15) 23 reactive groups (e.g., a nucicophilic group or a conjugatcd unsaturated group). [0073] -In some cases, the crosslinkable biomaterial can comprise a first precursor molecule which comprises an oligomer or polymer having one or more first reactive groups, cach first reactive group comprising one or more pi bonds, and a second precursor molecule comprises an oligomer or polymer having one or more second reactive groups, cach second reactive group comprising one or more pi bonds. The first reactive group can be reactive (e.g., via a Click chemistry reaction) with the second reactive group, so as to form a covalent bond hetween the first precursor molecule and the second precursor molecule. For example, the first reactive group and the second reactive group undergo a cycloaddition rcaction, such as a [3+2] cycloaddition (e.g., a Huisgen-type 1,3-dipolar cycloaddition hetween an alkync and an azidc) or a DiclsAider reaction. [0074] -In some cases, the crosslinkable biomaterial can comprise a first precursor molecule which comprises an oligomer or polymer having one or more nucicophilic groups (e.g. amino groups, thiol groups hydroxy groups, or combinations thercof), and a second prccursor molecule which comprises an oligomer or polymer having one or more conjugatcd unsaturated groups (e.g., vinyl sulfonc groups, acryl groups, or cornbinations thereof). In such cases, the first precursor molecule and the second precursor molecule can rcact via a Michael-type addition reaction. Suitablc conjugated unsaturated groups arc known in the art, and include those moictics descrihed in, for example, U.S. Patent Application Publication No. US 2008/0253987 to Rehor, et al., which is incorporated herein by reference in its entirety. [0075] In certain embodiments, the crosslinkable biomaterial can comprise a first precursor molecule and a second precursor molecule. The first precursor molecule comprises a poly(alkylene oxide)-based oligomer or polymer having x nucleophilic groups, wherein x is an integer greater than or equal to 2 (e.g., an integer of from 2 to 8, or an integer of from 2 to 6). The poly(alkylene oxide)-based polymer can comprise, for example, poly(ethylene glycol). The nucleophilic groups can be selected from the group consisting of sulthydryl groups and amino groups. The first precursor molecule can have a molecular weight of from about 1 kDa to about 10 kDa (e.g., from about 1 kDa to about 5 kDa). In some embodiments, the first precursor molecule comprises pentaerythritol poly(ethylene glycol)ether tetrasulfhydryl. [0076] The second precursor molecule can comprise a biomacromolecule having y conjugated unsaturated groups, wherein y is an integer greater than or equal to 2 (e.g., an integer of from 2 to 100, or an integer of from 2 to 25). The biomacromolecule can comprise a polysaccharide, such as dextran, hyaluronic acid, chitosan, alginate, or derivatives thereof. The conjugated unsaturated groups can be selected from the group consisting of vinyl sulfone groups and acryl groups. The second precursor molecule 24 can have a tnolecular wcight of from about 2 kDa to about 250 kDa (e.g., from about 5 kDa to about 50 kDa). In some embodiments, the second prccursor molccule comprises dcxtran vinyl sulfonc. [0077] In some cmbodiments, the in situ crosslinking of the prccursor molecules takcs place undcr basic conditions. In thcse emboditnents, the crosslinkahlc hiomatcrial can furthcr includc a hase to activatc the crosslinking of the prccursor molecules. A varicty of hases comply with the requirements of catalyzing, for example, Michacl addition rcactions undcr physiological conditions without hcing detrimental to the patient's body. Suitahle hases includc, but arc not limited to, tcrtiary alkyl-amines, such as trihutylamine, tricthylamine, ethyldiisopropylaminc, or N,N-dimethylhutylaminc. For a givcn composition (and mainly dcpendent on the type of prccursor molecules), the gclation tinic can Ir dcpendant on the type of hase and of the pH of the solution. Thus, the gclation time of the composition can Ir controlled and adjustcd to the dcsircd application by varying the pH of the basic solution. [0078] In some cmbodiments, the hase, as the activator of the covalent crosslinking reaction, is selected from aqucous huffer solutions which have thcir pH and pK value in the sanie range. The pK range can Ir between 9 and 13. Suitablc buffers include, but arc not limited to, sodium carbonate, sodium borate and glycine. In one cmbodiment, the hase is sodium carbonate. [0079] An example mcthod of dclivcring a hiomatcrial to a treatment site is also described generally as follows. This disclosure contemplates using the temperature-controlled systems desctibed above with respect to FIGS. 1-4 to deliver the biomaterial liquid to the treatment site. However, it is contemplated that the double banel syringe 100 depicted in FIGS. 5-6B for use with a crosslinkable biomaterial may also be used. [0080] With a patient lying on a radiolucent table, fluoroscopic guidance can optionally be used to percutaneously insert an introducer canula (e.g., the introducer cannula 200 shown in FIG. 3) into a body of a patient, where a distal end of the introducer cannula 200 is located inside the body of the patient and proximate a treatment site and a proximal end of the introducer cannula 200 is located outside the body of the patient (e.g., as shown in FIGS. 7 and 8). For example, as illustrated in Figure 7, the introducer cannula 200 is inserted into the posterior of an intervertebral disc 600. In addition to fluoroscopy, other ails, including but not limited to impedance monitoring and tactile feedback, may be used to assist a user to position the introducer or probe assemblies within the patient's body. Impedance monitoring allows the user to distinguish between tissues by monitoring impedance as a device is inserted into the patient's body. With respect to tactile feedback, different tissues may offer different amounts of physical resistance to an insertional force. This allows a user to distinguish between different tissues by feeling the force required to insert a device through a given tissue. if more than one probe 300 assemblies arc needed to facilitatc the treatment, additional introduecr cannulas 200 can he inserted into the patient in the sanie manner, and the stylets 400 removed. [0081] As described hercin, the introducer cannula can he uscd as the catheter through with RF ablation is performed. Probe assemblies 300 arc inscrted into each of introducers placing electrodes 322 proximate the tissue and/or nervous structure hcing trcated. Once in place, a stimulating clectrical signal may he cmitted from cither of clectrodes 322 to a dispersive clectrode or to the other clectrode 322 (if two arc uscd). This signal may hc uscd to stimulatc sensory ncrvcs whcre rcplication of symptomatie pain would vcrify proximity/placement at the targct nervous structure that the dise is pain-eausing. A different signal may be uscd to stimulatc motor nerves whcrc a motor rcaction indicatcs unsafc proximity to motor ncrves that should not be heated. As is well known in the art, various frequencies and voltages can be uscd to stimulatc hoth scnsory and motor nervcs. Observation of said stimulation can take the foret of visual, scnsory, mechanical, or clectrical détection of muscle activity, or the farm of sensory or clectrical detection of nociceptive or other scnsory neural activity (c.g. temperature sensation). The electrical energy ("stimulation energy") applicd during this step is beneficially capable of cliciting a response from a neural structure without damaging the neural structure. Using this step, it can be determined whether a targct nerve or nerves has a function that would contraindicatc its ablation or functional altcration. In one cmbodiment, the lack of a contraindication would lead to the step of delivering energy, whereas the presence of a contraindication would lead back to the step of inserting one or more probe assemblies, whereby the step of inserting a probe assembly includes modifying the position of a probe assembly within the body. Furthermore, in some embodiments, a method of this aspect of the present invention may comprise a step of stimulating neural tissue after a treatment procedure in order to determine the effectiveness of the treatment procedure. [0082] Probe assemblies 300 are connected to an RF generator 350 as well as to peristaltic pumps 340 to cool distal tip regions 312 of the probe 300. Radio frequency energy is delivered to electrodes 322 and the power is altered according to the temperature measured by a temperature sensing element provided on the tip of electrode 322 such that a desired temperature is reached between at the distal tip region 312. During the procedure, a treatment protocol such as the cooling supplied to the probe assemblies 300 and/or the power transmitted to the probe assemblies 300 may be adjusted in order to maintain a desirable treatment area chape, size and unifon-nity. The cooling devices may be independently controlled to alter the rate of cooling to the electrode 322. Following treatment, energy delivery and cooling are stopped and probe assemblies 106 are removed from introducers. 26 [0083] The mcthod can also include inscrting a dclivcry tip of a syringc (e.g., the syringc 100 shown in FIGS. 1 A-2 and 5-6B) into the proximal end of the introduccr cannula 200. As described herein with respect to FIGS. 1A-2, a biomaterial such as a stimuliresponsive biomaterial, e.g., a thermoresponsive polymer cornprising a poloxamer, can he containcd within a body of the syringc. Likcwisc, as descrihed with respect to FIGS. 5-6B, a crosslinkahlc biomaterial can he containcd with the body of the syringe. As described abovc, the biomaterial can he used before, during and aftcr an RF ablation procedure to insulate various tissue structures, conduct and direct the clectrical signal to target tissue, to facilitatc cooling of the treatment site, for drug delivery to the targct nervous structure and/or surrounding tissue, to creatc a physical harrier hctwccn the target nerve and the surrounding tissue, and/or to facilitate additional and/or continucd modulation of the target nervous structure. Accordingly, in an example trcatmcnt mcthod, with the probe 300 removcd from the introducer cannula 200, the needld cannula 132 is inscrted into the introducer cannula 200 (FIG. 8), the plunger is dcpressed, and the biomatcrial is introduced to thc treatment site. In anothcr example, with the probe 300 maintaincd within the introducer cannula 200, the needle/cannula 132 is insertcd into the introducer cannula 200, the plunger dcpressed, and the biomaterial is introduced into the trcatrncnt site. [0084] Optionally, the dclivcry tip 130 can he coupled to thc proximal end of the introducer cannula 200 to provide a liquid-tight fit. However, whcre the syringc 100 does not include a needle/cannula 132 the delivery tip 130 is coupled to the proximal end of the introducer cannula 200 to provide a liquid-tight fit. Optionally, the method can include moving the introducer cannula 200 and syringe 100 from a locked to an unlocked configuration, for example, using engagement features (e.g., the engagement features 106, 206 shown in FIGS. 1A-2) to allow depression of the plunger 104. [0085] Where the biomaterial comprises a thermoresponsive polymer, the method can further include maintaining the thennoresponsive polymer at a temperature below its liquid-solid phase transition temperature. The plunger 104 of the syringe 100 is depressed to advance the thennoresponsive polymer in its liquid state through a delivery tip 130 of the syringe 100 and to the treatment site. Following injection, the liquid composition can form a polymeric matrix at (e.g., a solid or gel) at the treatment site upon injection into a physiological environment. The polymeric matrix can substantially surround the lesion, thereby modulating neural regeneration at the lesion site. For example, the polymeric matrix can lirait or prevent macrophages from accessing the lesion site. Macrophages secrete growth factors that drive neurogenesis at the proximal end of the nerve. By limiting and/or preventing the ability of macrophages to access the lesion site, the quantity of neural growth factors reaching the lesion site (and by extension nerve growth at the proximal end of the nerve) can be controlled. If 27 desired, active agents to control nerve growth can also he incorporated in the polymcric matrix. In these embodiments, the polymcric matrix can funetion as a dcpot, providing for controllcd, local delivering these active agents at the lesion site. Thus, neural regeneration at the lcsion site can he guided and controlled using a polymcric matrix, therehy prolonging the pain-relieving effects of the neural ablation procédures. [0086] Where the hiomaterial comprises a thermoresponsive polymer, the mcthod can include cooling the syringe 100, the introduccr cannula 200, and/or thermoresponsive polymcr to a temperature below the liquid-solid phase transition temperature of the thermoresponsive polymcr. This can he accomplishcd, for example, using a cooling mcchanism, c.g., the cooling mcchanism 150 shown in FIGS. 1 A-2). The method can be performed during an RF ablation procedure. In this implementation, the mcthod can optionally includc cooling the introduccr cannula using a coolcd RF probe (e.g., the coolcd RF probe 300 shown in FIG. 2). Altcrnativcly or additionally, this can he accomplished, for example, using a cooling mechanism (e.g., the second cooling mcchanism 250 shown in FIG. 4). Optionally, the introduccr cannula can he coolcd to a temperature bclow the liquid-solid phase transition temperature of the thermoresponsive polymer. [0087] Although the subject matter has heen described in language specific to structural features and/or methodological acts, it is to he understood that the suhject matter defined in the appended claims is not necessarily limited to the specific features or acts described above. Rather, REVENDICATIONS1. A temperature-controlled system for del ivering a stimuli-responsive biomatcrial to a treatment site, the system comprising: a syringe including: a body defining a volume for containing a thermoresponsive polymcr liquid, a distal end of the body includes a delivery tip, and a plunger sized and configured to move within the volume of the body to convey the thermoresponsive polymer liquid through the delivery tip, wherein the syringe maintains the thermoresponsive polymer liquid at a temperature below its liquid-solid phase transition temperature. The system of daim 1, wherein the body of the syringe includes a cooling mechanism for maintaining an interior surface of the body at a temperature below the liquid-solid phase transition temperature of the thermoresponsive polymer liquid. The system of daim 2, wherein the cooling mechanism includes at least one of an insulative material provided around the body of the syringe, a cooling pad coupled to the exterior of the body of the syringe, a chilled water system where a volume of chilled water is flowed around the body of the syringe, and a thermoelectric cooler. The system of daim 2, wherein the body of the syringe is fonned from a double wall vacuum insulated material. The system of any of daims 1-4, further comprising: an elongated introducer cannula including a central channel sized and configured to receive the delivery tip of the syringe, and a cooled radiofrequency (RF) probe sized for insertion into the central channel of the introducer cannula, the cooled RF probe being configured to circulate water at a temperature that maintains the introducer cannula at a temperature below die liquid-solid phase transition temperature of the thermoresponsive polymer liquid. The system of daim 5, wherein the introducer cannula includes at least one of an insulative material provided around the introducer cannula, a double wall vacuum insulated material, a cooling pad coupled to the introducer cannula, a thermoelectric cooler, or a chilled water system for flowing a volume of chilled water around the introducer cannula. The system of any of daims 1-6, wherein an interior surface of the body of the syringe is maintained at a temperature below about body 29 temperature, wherein the interior surface of die hody of the syringc is tnaintained at a temperature hetween about 28°C and about 42°C. [Claim 8] The system of any of daims 1-7, whercin an interior surface of the hody of the syringc is maintaincd at a temperature helow about room temperature, wherein the interior surface of the hody of the syringc is tnaintained at a temperature hetween about 19°C and about 25°C. [Claim 9] The system for delivering a hiomaterial to a radio frequency ablation treatment site, the system comprising: a syringc including: a hody defining a volume for containing a hiomaterial, a distal end of the hody includcs a delivery tip, and a plunger sized and configured to [nove within the volume of the hody to convey the hiomaterial through the delivery tip, and an clongated introducer cannula including: a central channel sized and configured to receive the delivery tip of the syringc, an engagement feature provided at a proximal end of the introducer cannula for coupling with a corresponding engagement feature provided at a distal end of the syringc, wherein the syringe and introducer cannula arc movahle hetween an unlocked and locked configuration, where in the unlocked configuration the syringe ami introducer cannula engagement features are not coupled, and where in the locked configuration the syringe and introducer engagement features are coupled. [Claim 10] The system of daim 9, wherein in the unlocked configuration axial movement of the plunger within the volume of the body is prohibited, preventing flow of the biomaterial through the delivery tip, wherein in the locked configuration axial movement of the plunger within the volume is permitted thereby providing flow of the biomaterial through the delivery tip and into the introducer cannula. [Claim 11] The system of any of daims 9-10, further comprising a restraint mechanism coupled to the plunger, wherein the restraint mechanism is configured to restrict axial movement of the plunger within the volume. [Claim 12] The system of any of daims 9-11, wherein the engagement feature provided at the proximal end of the introducer cannula is a female Luer fitting, wherein the engagement feature provided at the distal end of the syringe is a male Luer fitting, and 30 wherein rotational tnovement between the male and female Lucr fittings results in secured coupling between the introduccr cannula and the syringe. [Claim 13] The system of any of daims 9-12, wherein the engagement feature provided at the proximal end of the introduccr cannula includes at least one of a recess, a projection, a tapered surface for press fitting with the syringc, a clip, a thread, a bayonct mount, wherein the engagement feature provided at the distal end of the syringc comprising a corresponding at least one of a projection, a mecs s, a tapered surface for press fitting with the introduccr cannula, a clip, a thrcad, and a bayonct mount, wherein coupling movement between the engagement features of the introduccr cannula and syringc results in a secured coupling between the introduccr cannula and the syringc. [Claim 14] The system of any of daims 9-13, wherein at least a portion of the delivery tip is couplcd to the proximal end of the introduccr cannula and extends at least partially into the central channel of the introduccr cannula. [Claim 15] A system for delivering a crosslinkable hiomaterial to a treatment site, the system comprising: a syringe including: a body defining a first volume for containing a first precursor and a separate second volume separate from the first volume for containing a second precursor, a distal end of the body includes a delivery tip, and a plunger sized and configured to move within the first and second volumes of the body to convey the first and second precursors through the delivery tip, wherein the delivery tip includes an elongated needle defining a first bore and a separate second bore, wherein the fu-st bore is in tluid communication with the first volume of the syringe and the second bore is in tluid communication with the second volume of the syringe, such that the first precursor and the second precursor transmitted through the needle combine as they pass through a distal end of the needle.