Patent Description:
Conventionally, bone tissue regeneration is achieved by filling a bone defect with a bone material, for example, a bone graft. Over time, the bone graft is incorporated by the host and new bone remodels the bone graft. Bone material can include bone from the patient's own body, synthetic bone material, natural substitute bone material or combinations thereof.

To deliver the bone material to the bone defect, often times the bone material is mixed with liquid or a therapeutic agent, powder, fiber or granular material. Further, transfer of bone material to the dispensing device is often done by crude and messy packing of the bone dispensing device which can cause unwanted waste and spillage of bone material. During transfer and delivery of the bone material, these devices can also increase the risk of contamination of the bone material. Additionally, some dispensing devices can cause damage to surrounding tissue of a surgical site during administration of the bone material. Moreover, bone material can clog certain dispensing devices due to its consistency and/or due to the design of the dispensing device and the amount of bone material cannot be controlled effectively when this occurs.

It would therefore be desirable to provide a bone material dispensing device that allows easier loading of the bone material, which reduces the risk of contamination and spillage of bone material from the dispensing device. It would also be beneficial to provide a dispensing device that reduces clogging during dispensing of the bone material and is also able to deliver the bone material incrementally in controlled amounts to a bone defect. Various bone material dispensing devices are known, e.g., from <CIT>, <CIT> or <CIT>. <CIT> discloses a bone graft delivery apparatus comprising a housing including a barrel and a handle. A magazine is coupled to the housing and has a plurality of chambers. Each of the chambers is configured to support a bone graft. A plunger is supported by the housing and is configured to selectively pass through one of the chambers and along the barrel. A selector knob is operably coupled to a plurality of stops that are coupled to the plunger. The selector knob is movable into a plurality of positions, wherein each position employs one of the stops. A trigger mechanism is supported by the housing and is operably coupled to the plunger to advance the plunger along the barrel. A first of the stops prevents the plunger from being moved forward past a first predetermined plunger position when the selector knob is in a first of the positions. A second of the stops prevents the plunger from being moved forward past a second predetermined plunger position when the selector knob is in a second of the positions. <CIT> discloses a delivery apparatus for delivering material to a medical treatment site which comprises a plurality of containers for containing the material, a dispensing outlet and means for bringing each container into communication with the outlet and means for transferring material from the containers and through the outlet. The plurality of containers may be removably mounted within a removable cartridge. The apparatus is arranged so that the cartridge is biased to sequentially move each of the containers into communication with the outlet. The outlet may be provided at the end of a dispensing nozzle where the dispensing nozzle has an inner cross-sectional area that is uniform and the same as the containers so that no taper is provided as the material is dispensed from the containers and out of the outlet. <CIT> discloses a graft material injector device. The injector device includes an elongated injector tube and a side loading aperture for receiving graft material. A graft material loader and a cover for the side loading aperture may optionally be included.

The bone material dispensing device of the present invention reduces the risk of contamination and spillage of bone material from the dispensing device, administers the bone material to a bone defect and reduces clogging during incremental dispensing of the bone material.

The invention provides a bone material dispensing device to administer bone material according to claim <NUM> and a method for loading the bone material dispensing device according to claim <NUM>. Further embodiments of the invention are described in the dependent claims.

While multiple embodiments are disclosed, still other embodiments of the present disclosure will become apparent to those skilled in the art from the following detailed description. As will be apparent, the disclosure is capable of modifications in various obvious aspects, all without departing from the scope of the present disclosure. Accordingly, the detailed description is to be regarded as illustrative in nature and not restrictive. <FIG> do not show an embodiment claimed as such, but may help understanding aspects of the invention.

In part, other aspects, features, benefits and advantages of the embodiments will be apparent with regard to the following description, appended claims and accompanying figures.

It is to be understood that the figures are not drawn to scale. Further, the relation between objects in a figure may not be to scale, and may in fact have a reverse relationship as to size. The figures are intended to bring understanding and clarity to the structure of each object shown, and thus, some features may be exaggerated in order to illustrate a specific feature of a structure.

It is noted that, as used in this specification and the appended claims, the singular forms "a," "an," and "the," include plural referents unless expressly and unequivocally limited to one referent.

The term "allograft" refers to a graft of tissue obtained from a donor of the same species as, but with a different genetic make-up from, the recipient, as a tissue transplant between two humans.

The term "autologous" refers to being derived or transferred from the same individual's body, such as for example an autologous bone marrow transplant.

The term "xenograft" refers to tissue or organs from an individual of one species transplanted into or grafted onto an organism of another species, genus, or family.

The term "mammal" refers to organisms from the taxonomy class "mammalian," including, but not limited to, humans; other primates, such as chimpanzees, apes, orangutans and monkeys; rats, mice, cats, dogs, cows, horses, etc..

The term "patient" refers to a biological system to which a treatment can be administered. A biological system can include, for example, an individual cell, a set of cells (e.g., a cell culture), an organ, or a tissue. Additionally, the term "patient" can refer to animals, including, without limitation, humans.

The term "bone material" includes natural and/or inorganic material such as, for example, inorganic ceramic and/or bone substitute material. The bone material can also include natural bone material such as, for example, bone which is cortical, cancellous or cortico-cancellous of autogenous, allogenic, xenogenic, or transgenic origin. In some embodiments, bone material can include demineralized bone material such as, for example, substantially demineralized bone material, partially demineralized bone material, or fully demineralized bone material.

"Demineralized" as used herein, refers to any material generated by removing mineral material from tissue, e.g., bone tissue. In certain embodiments, the demineralized compositions described herein include preparations containing less than <NUM>% calcium and preferably less than <NUM>% calcium by weight. Partially demineralized bone (e.g., preparations with greater than <NUM>% calcium by weight but containing less than <NUM>% of the original starting amount of calcium) is also considered within the scope of the application. In some embodiments, demineralized bone has less than <NUM>% of its original mineral content.

The unit "inches" used throughout the description is converted to "millimeters" (mm) as follows: <NUM> inch = <NUM>,<NUM>.

The unit "ounces" (oz) used throughout the description is converted to "grams" (g) as follows: <NUM> oz = <NUM>,<NUM>.

In some embodiments, demineralized bone has less than <NUM>% of its original mineral content. In some embodiments, demineralized bone has less than <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> and/or <NUM>% of its original content. In some embodiments, "demineralized" is intended to encompass such expressions as "substantially demineralized," "superficially demineralized," "partially demineralized," "surface demineralized," and "fully demineralized.

"Partially demineralized" is intended to encompass "surface demineralized. " "Partially demineralized bone" is intended to refer to preparations with greater than <NUM>% calcium by weight but containing less than <NUM>% of the original starting amount of calcium. In some embodiments, partially demineralized comprises <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> and/or <NUM>% of the original starting amount of calcium.

In some embodiments, the demineralized bone may be surface demineralized from about <NUM>-<NUM>%. In some embodiments, the demineralized bone is <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> and/or <NUM>% surface demineralized. In various embodiments, the demineralized bone may be surface demineralized from about <NUM>-<NUM>%. In some embodiments, the demineralized bone is <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> and/or <NUM>% surface demineralized.

"Superficially demineralized" as used herein, refers to bone-derived elements possessing at least about <NUM> weight percent of their original inorganic mineral content, the expression "partially demineralized" as used herein refers to bone-derived elements possessing from about <NUM> to about <NUM> weight percent of their original inorganic mineral content and the expression "fully demineralized" as used herein refers to bone containing less than <NUM>% of its original mineral context.

"Demineralized bone matrix" as used herein, refers to any material generated by removing mineral material from bone tissue. In preferred embodiments, the DBM compositions as used herein include preparations containing less than <NUM>% calcium and preferably less than <NUM>% calcium by weight.

"Biocompatible" as used herein, refers to materials that, upon administration in vivo, do not induce undesirable long-term effects.

"Osteoconductive" as used herein, refers to the ability of a non-osteoinductive substance to serve as a suitable template or substance along which bone may grow.

"Osteogenic", as used herein, refers to the ability of an agent, material, or implant to enhance or accelerate the growth of new bone tissue by one or more mechanisms such as osteogenesis, osteoconduction, and/or osteoinduction.

"Osteoinductive" as used herein, refers to the quality of being able to recruit cells from the host that have the potential to stimulate new bone formation. Any material that can induce the formation of ectopic bone in the soft tissue of an animal is considered osteoinductive. For example, most osteoinductive materials induce bone formation in athymic rats when assayed.

The terms "upper", "lower", "top", "bottom", "side", "proximal", "distal" and so forth have been used herein merely for convenience to describe the present invention and its parts as oriented in the drawings. It is to be understood, however, that these terms are in no way limiting to the disclosure since the dispensing systems described herein may obviously be disposed in different orientations when in use.

The term "removably engage" includes engagement of two or more components that can be used or combined into one element via the engagement of the two or more elements with a connecting means, a locking means, or by placing the elements tightly together. The two or more elements may be positioned adjacent to each other and each include a contacting surface.

For the purposes of this specification and appended claims, unless otherwise indicated, all numbers expressing quantities of ingredients, percentages or proportions of materials, reaction conditions, and other numerical values used in the specification and claims, are to be understood as being modified in all instances by the term "about. " Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the present invention. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.

Notwithstanding the numerical ranges and parameters set forth herein, the broad scope of the invention is an approximation; the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements. Moreover, all ranges disclosed herein are to be understood to encompass any and all subranges subsumed therein. For example, a range of "<NUM> to <NUM>" includes any and all subranges between (and including) the minimum value of <NUM> and the maximum value of <NUM>, that is, any and all subranges having a minimum value of equal to or greater than <NUM> and a maximum value of equal to or less than <NUM>, e.g., <NUM> to <NUM>.

Reference will now be made in detail to certain embodiments of the disclosure, examples of which are illustrated in the accompanying figures. While the disclosure will be described in conjunction with the illustrated embodiments, it will be understood that they are not intended to limit the disclosure to those embodiments. On the contrary, the disclosure is intended to cover all alternatives, modifications, and equivalents that may be included within the disclosure as defined by the appended claims.

The headings below are not meant to limit the disclosure in any way; embodiments under any one heading may be used in conjunction with embodiments under any other heading.

A bone material dispensing device <NUM> is provided that is used to administer bone material to a surgical site in incremental amounts, as shown in <FIG>. The bone material dispensing device can be a bone material dispensing gun that reduces the risk of contamination and spillage of bone material from the dispensing device, and administers the bone material to a surgical site (e.g., bone defect) while reducing damage to surrounding tissue. The bone material dispensing device reduces clogging and allows incremental dispensing of the bone material. The bone material dispensing device is also configured for left handed and right handed use. A surgical site can include, but is not limited to injury, defects brought about during the course of surgery, infection, malignancy or developmental malformation. Specific bones which can be repaired or replaced with the bone material can include, but are not limited to the ethmoid; frontal; nasal; occipital; parietal; temporal; mandible; maxilla; zygomatic; cervical vertebra; thoracic vertebra; lumbar vertebra; sacrum; rib; sternum; clavicle; scapula; humerus; radius; ulna; carpal bones; metacarpal bones; phalanges; ilium; ischium; pubis; femur; tibia; fibula; patella; calcaneus; tarsal and metatarsal bones. In some embodiments, the bone material dispensing device administers bone material to at least a portion of the spinal cord such as vertebrae or a vertebra V1, as shown in <FIG>.

The bone material dispensing device includes a housing <NUM> having a proximal end <NUM>, a distal end <NUM>, and a longitudinal axis AA disposed therebetween. The proximal end of the housing includes a first opening <NUM> and the distal end includes a second opening <NUM>. The first opening and the second opening are configured to slidably receive at least a portion of a plunger <NUM>, as described herein.

The first opening has a diameter D1 and the second opening has a diameter D2, as shown in <FIG>. D1 and D2 are the same diameter. In some embodiments, D1 and D2 can have different diameters. In some embodiments, the diameters D1 and D2 can be from about <NUM> millimeters (mm) to about <NUM>. The diameters can be from about <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> to about <NUM>. The first and second openings can be shaped and can be round, oval, rectangular or square.

The plunger, as described herein, has a proximal end <NUM> and a distal end <NUM>. The plunger is configured to assist in the dispensing/administration of the bone material to a surgical site, as described herein. This allows for controlled and incremental administration of the bone material to the bone defect. In some embodiments, the proximal end or the distal end of the plunger can include a rim and/or a pushplate to assist in dispensing the bone material. The diameter D3 of the plunger is smaller than diameters D1 and D2, as shown in <FIG>. In some embodiments, the diameter D3 of the plunger is slightly smaller than diameters D1 and D2 but allows at least a portion of the plunger to slide within the openings. In some embodiments, diameter D3 can be from about <NUM> millimeters (mm) to about <NUM>. The diameter D3 can be from about <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> to about <NUM>. The plunger can also have a certain length L1 of from about <NUM> to about <NUM> inches, as shown in <FIG>. In some embodiments, the length L1 of the plunger can be from about <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> to about <NUM> inches. The plunger length can be smaller, larger or the same size as the cannula, as described herein. In some embodiments, the plunger can be flexible or rigid.

The bone material dispensing device includes a tubular member <NUM> that is pivotably connected to the housing and is configured for lateral movement relative to longitudinal axis AA of the housing. The tubular member includes a proximal end <NUM>, a distal end <NUM> and longitudinal axis AA is disposed therebetween when the tubular member is in a first position, as described herein. The tubular member can be conical and the distal end can be tapered.

The proximal end of the tubular member includes a proximal opening <NUM> and the distal end of the tubular member includes a distal opening <NUM>. A channel <NUM> is disposed therebetween. The proximal opening, the distal opening and the channel of the tubular member are configured to receive at least a portion of the plunger such that when bone material is disposed within the channel, the plunger can be advanced into the channel to dispense or administer the bone material, as described herein. For example, the tubular member is movable in a first position to align the proximal opening of the tubular member with the second opening of the housing to allow the tubular member to receive at least the portion of the plunger (as shown in <FIG>) to dispense the bone material. The tubular member is also movable in a second position to misalign the proximal opening of the tubular member with the second opening of the housing to prevent the tubular member from receiving at least the portion of the plunger.

As described above, the tubular member is pivotably connected to the housing via a pivot point, such as a hinge <NUM>. The hinge is transverse relative to longitudinal axis AA. The hinge facilitates rotation of the tubular member relative to the housing in the directions shown by arrows A and B, shown in <FIG>. The hinge can alternatively be or can include a pivot pin, or a rod. The tubular member pivots towards and away from the housing at an angle α1 of from about <NUM> to about <NUM> degrees, as shown in <FIG>. In some embodiments, α1 is from about <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> to about <NUM> degrees. The tubular member can be pivoted so that there is enough space provided for the tubular member to be loaded with bone material.

The tubular member locks with a portion of the distal end of the housing via a detent <NUM> that is located between the tubular member and the housing. The detent locks the tubular member in the first position, as described above. The detent can be a catch, a lever, a spring, a hinged catch that engages a notch of a ratchet, or a combination thereof. The locking will allow the openings to align (as shown in <FIG>) and the plunger to be slid through the openings. In some embodiments, when the tubular member is swiveled open, the holes are misaligned and the plunger cannot be slid through the tubular member, as shown in <FIG>.

In some embodiments the tubular member can be entirely detachable and can snap connect to the housing. In some embodiments, the tubular member can be entirely detachable and connect with a screw-on thread form to the housing. In some embodiments, the tubular member can be pivotably connected to the housing in a similar manner to a breach loaded shot-gun. It should be noted that one of ordinary skill in the art can modify the tubular member and its connection to the housing to adjust the design of the bone material dispensing device.

The housing includes a trigger assembly <NUM>, as shown in <FIG> that is configured to allow incremental slidable movement of the plunger to dispense the bone material, as described herein. The trigger assembly includes a driving handle <NUM> and a stationary handle <NUM>. The driving handle includes a proximal end <NUM>, a distal end <NUM> and a longitudinal axis BB disposed therebetween. The proximal end of the driving handle is configured for pivotable engagement with an intermediate portion of the stationary handle and a proximal end of a driving pawl, as described below. The proximal end of the driving handle includes an extension <NUM>, as shown in <FIG>. The extension has an angle α2, as shown in <FIG>. The extension can have an angle α2 from about <NUM> to about <NUM> degrees. In some embodiments, the extension can have an angle α2 of from about <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> to about <NUM> degrees. The extension is configured for engagement with a proximal end of a driving pawl, as described below.

The proximal end of the driving handle includes a recess <NUM> that is distal to the extension. The recess is configured for engagement with a pin <NUM> such that the proximal end of the driving handle pivotable engages with the stationary handle, as described herein.

A surface <NUM> of the driving handle includes gripping surfaces <NUM> and a projection <NUM>, as shown in <FIG>. The gripping surfaces and the projection are configured for engagement with a user's hand such that the driving handle can be controlled effectively by the user. The gripping surfaces can be raised or straight and the projection can be curved or straight. The gripping surface can also be roughened to increase the control that the user has over the driving handle.

The surface of the driving handle can also define cutouts <NUM>. The cutouts can be oval, round, square, triangular, rectangular or any other regular or irregular shape. There can be one or more cutouts formed from the surface of the driving handle, such as <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> or more cutouts. The user moves the driving handle in the direction of the stationary handle. The driving handle engages the active pawl, which slides the plunger longitudinally and incrementally in the direction of the distal end. This allows for bone material to be incrementally dispensed from the bone material dispensing device.

The stationary handle includes a proximal end <NUM>, an intermediate portion <NUM>, a distal end <NUM> and a longitudinal axis CC disposed between the proximal end and the distal end. The proximal end of the stationary handle includes a first side <NUM>, a second side <NUM> and a third side <NUM>. The first, second and third sides are part of the housing. The proximal end of the stationary handle can be monolithic with the housing and the first, second and third sides can be monolithic or fixed to the stationary handle. Portions of the first side and the second side form part of hinge <NUM>, as shown in <FIG> and <FIG>. The third side includes a slot <NUM> that is configured for engagement with a portion of a passive pawl, as described herein and shown in <FIG>.

The intermediate portion of the stationary handle is configured for engagement with the proximal end of the driving handle. A recess <NUM>, as shown in <FIG> is formed in the intermediate portion and is configured for engagement with pin <NUM>, as shown in <FIG> such that the proximal end of the driving handle pivotable engages with the stationary handle, as described herein and shown in <FIG>. The driving handle pivots toward and away from the stationary handle at an angle α3 of from about <NUM> to about <NUM> degrees, shown in <FIG> and <FIG>. In some embodiments, α3 is from about <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> to about <NUM> degrees.

A recess <NUM>, as shown in <FIG>, is formed in a portion of the second side of the stationary handle and is configured for engagement with a pin <NUM> such that a passive pawl can pivotably engage with the housing, as described herein and shown in <FIG>. In some embodiments, the stationary handle and the housing are monolithic with one another. In some embodiments, the stationary handle and the housing are not monolithic.

The trigger assembly of the housing further includes a driving pawl <NUM> and a passive pawl <NUM>. The driving pawl is configured to work in conjunction with a resilient member to assist the stationary handle and the driving handle in incremental slideable movement of the plunger such that the plunger dispenses the bone material. In the embodiment shown in <FIG>, the resilient member shown as a spring is concentric with the plunger. On movement of the driving handle to the stationary handle, the spring is compressed and the stored energy pushes the plunger longitudinally in increments. The driving pawl is disposed at one end of the resilient member and the other end of the resilient member biases against the housing and plunger.

The driving pawl includes a first end <NUM> and a second end <NUM>, as shown in <FIG>. The first end of the driving pawl is configured for movable engagement with the extension of the driving handle. The first end of the driving pawl can have a concave portion <NUM> that engages with the extension of the driving handle. The driving pawl includes a third opening <NUM> that is in alignment and in between the first opening and the second opening of the housing, as shown in <FIG>. The third opening is configured to slidably receive at least a portion of the plunger <NUM>, as described herein. The third opening can be centrally located on the driving pawl.

The third opening has a diameter D4, as shown in <FIG>. D4 can be the same diameter as D1 and D2, and D4 has a greater diameter than plunger diameter D3. In some embodiments, D4 can have a different diameter than D1 and D2. In some embodiments, diameter D4 can be from about <NUM> millimeters (mm) to about <NUM>. Diameter D4 can be from about <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> to about <NUM>. The third opening can be shaped and can be round, oval, rectangular or square.

The second end of the driving pawl includes a lever <NUM> that is configured for slidable engagement with the slot of the third side of the stationary handle. The lever can be variously shaped, including but not limited to T-shaped, as shown in <FIG>.

The passive pawl includes a first end <NUM>, and a second end <NUM>, as shown in <FIG>. The passive pawl is configured to work in conjunction with a resilient member to control when the plunger is advanced during dispensing of the bone material and retracted after dispensing or reloading of the bone material. The passive pawl allows the plunger to be adjusted so that the plunger can be located adjacent to the bone material and if more bone material is added to the cannula or the tubular member, the plunger can be adjusted to be placed adjacent to the additional bone material. In this way, the bone material dispensing device can easily accommodate various quantities of bone material.

The first end of the passive pawl can be angled. The second end of the passive pawl includes a recess <NUM> configured for engagement with pin <NUM> such that the passive pawl can pivotably engage with the housing, as shown in <FIG>. The passive pawl can pivot at an angle α4 of from about <NUM> to about <NUM> degrees, as shown in <FIG>. In some embodiments, α4 is from about <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> or from about <NUM> degrees.

The passive pawl includes a fourth opening <NUM> that is above and in alignment with the first opening and the second opening of the housing, and the third opening of the driving pawl, as shown in <FIG>. The fourth opening is configured to slidably receive at least a portion of the plunger <NUM>, as described herein. The fourth opening can be centrally located on the passive pawl.

The fourth opening has a diameter D5, as shown in <FIG>. D5 can be the same diameter as D1, D2 and D4, and has a greater diameter than plunger diameter D3. In some embodiments, D5 can have a different diameter than D1, D2 and D4. In some embodiments, diameter D5 can be from about <NUM> millimeters (mm) to about <NUM>. Diameter D5 can be from about <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> to about <NUM>. The fourth opening can be shaped and can be round, oval, rectangular or square.

A recess <NUM> is located on an underside of the passive pawl, shown in <FIG> and is configured for engagement with an end of a resilient member, as described herein. The recess can be variously shaped, such as, for example, rectangular, round, oval or square.

The trigger assembly includes a first resilient member, such as a first spring <NUM> that is configured for engagement with the passive pawl, as described herein. The first spring is disposed between a first portion <NUM> of the housing and the passive pawl, as shown in <FIG>. The first spring comprises a distal end <NUM> configured for engagement with a stanchion <NUM> located on the first portion of the housing, and a proximal end <NUM> which is disposed within recess <NUM> located on the underside of the passive pawl. The first spring is adjacent to the fourth opening or plunger, and can also be concentric to the plunger. On moving the passive pawl toward the stationary handle, the first spring can be compressed and store energy, which will allow the plunger to be withdrawn or adjusted to allow bone material to be added to the cannula.

The trigger assembly includes a second resilient member, such as second spring <NUM> that is configured for engagement with the driving pawl, as described herein. The second spring is disposed concentric to the plunger and is disposed between a second portion <NUM> of the housing and the driving pawl, as shown in <FIG>. The second spring comprises a distal end <NUM> that engages with second opening <NUM> of the housing, and a proximal end <NUM> that engages with first opening <NUM> of the housing. At least a portion of the plunger is configured to be slidably received by the second spring, as described herein.

In some embodiments, the tubular member is configured to engage with a cannula, such as, for example, a folding cannula <NUM>, as shown in <FIG>, which is not according to the invention and is present for illustration purposes only. The folding cannula is configured to be loaded with the bone material and engages the tubular member and/or the plunger for dispensing the bone material into a surgical site, as shown in <FIG>. The folding cannula comprises a proximal end <NUM> and a distal end <NUM>. The folding cannula is segmented into an upper compartment <NUM> and a lower compartment <NUM>, and the folding cannula is movable in a folded configuration (<FIG>) and an unfolded configuration (<FIG>) about a fold line <NUM>.

The folding cannula has a diameter D6 that is larger than a diameter D7 of distal opening <NUM> of the tubular member so as to allow at least a portion of the folding cannula to be held within the tubular member, as shown in <FIG>, <FIG> and <FIG>. In some embodiments, diameter D6 can be from about <NUM> millimeters (mm) to about <NUM>. The diameter D6 can be from about <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> to about <NUM>. The folding cannula can have differing diameters throughout the folding cannula and does not have to have a uniform diameter. The diameter D7 has a larger diameter than the plunger diameter D3. The diameter D7 can be from about <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> to about <NUM>.

In some embodiments, the folding cannula engages with a funnel or funnel portion <NUM> that is configured to removably engage and partially enclose the tubular member, as shown in <FIG> and <FIG>. The funnel portion matingly engages conically with the distal end of the tubular member. As shown in <FIG>, the funnel portion includes a proximal end <NUM> and a distal end <NUM>. The proximal end engages with a portion of the housing to lock the funnel portion to the housing via a locking member <NUM>, as shown in <FIG>. It will be understood that shown is a cross sectional view of the cannula and the funnel portion. The distal end of the funnel portion can be various dimensions and can be a certain length L2, such as <NUM> to about <NUM> inches. In some embodiments, the length of the distal end of the funnel portion can be from about <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> to about <NUM> inches. In some embodiments, a dog-point can be added between the housing and the funnel portion to provide an even more secure engagement between the housing and the funnel portion. In some embodiments, the funnel portion is separate or is a component of the folding cannula. In some embodiments, the funnel portion is flexible or rigid, or only one of the funnel portion or the plunger is flexible. In operation, to load the bone material dispensing device with bone material, the tubular member is rotated in the direction of arrow B, as shown in <FIG>. The tubular member is then loaded with the bone material, or the folding cannula is loaded with the bone material and inserted into the proximal end of the tubular member so that at least a portion of the folding cannula is held within the tubular member and at least a portion of the folding cannula is fed through the distal opening of the tubular member, as shown in <FIG>. The tubular member is then moved about hinge <NUM> in a first position, as shown by arrow A in <FIG> and the funnel portion engages with the tubular member and/or the combination tubular member and the folding cannula. The funnel portion is then locked onto the housing via the locking member, as shown in <FIG>.

The distal end of the funnel portion is then inserted into a surgical site, such as, for example, vertebra V1, as shown in <FIG>. The distal end of the funnel portion can be inserted into the surgical site before or after the funnel portion is locked onto the housing, as shown in <FIG> and <FIG>. For example, the funnel portion can be placed at the surgical site first and then locked with the housing. In the first position, the proximal opening of the tubular member is aligned with the second opening of the housing to allow the tubular member to receive at least the portion of the plunger to dispense the bone material. The plunger is then translated in the direction of arrow F shown in <FIG> and <FIG>, into the fourth opening of the passive pawl, the first opening of the housing, the third opening of the driving pawl and the second opening of the housing via the trigger assembly.

The driving handle of the trigger assembly contacts the first end of the driving pawl, as shown in <FIG>, when the driving handle is moved toward the stationary handle in the direction shown by arrow C in <FIG> and <FIG>, and movement of the driving handle toward the stationary handle causes the driving pawl to compress the second spring in the direction shown by arrow D in <FIG> and transient energy from the compressed second spring allows incremental slidable movement of the plunger, as shown by arrow E in <FIG>. Since diameter D4 of the third opening of the driving pawl is slightly larger than diameter D3 of the plunger, and the driving pawl is driven off axis using extension <NUM> of the driving handle, as the driving handle presses downward on the driving pawl it tilts and diameter D4 becomes the same size as diameter D3, pinching the plunger. Any further advancement of the driving handle results in the driving pawl pinching the plunger harder and advancing the plunger. As soon as the pressure on the driving handle is released, the second spring pushes up on the driving pawl again increasing the size of D4, allowing the driving pawl to slide back up the plunger, returning it to the starting position to push again.

Movement of the driving handle toward the stationary handle also causes the first spring to be compressed against the first portion of the housing by the passive pawl. The driving handle is released and the driving handle moves in the direction shown by arrow G of <FIG>. The proximal end of the passive pawl is then pushed in a downward direction, as shown by arrow H in <FIG> to again compress the first spring so that the first spring contains transient energy such that the user can retract the plunger in a proximal direction, as shown by arrow I of <FIG> and <FIG>. The advancement and retraction of the plunger can be controlled by the passive pawl and the first spring. For example, the passive pawl pinches the plunger, preventing the plunger from retracting while the driving pawl is returned to its starting position. Further, the passive pawl allows the plunger to move through the fourth opening because the passive pawl pivots and is spring loaded via the first spring.

Once the bone material dispensing device is finished dispensing bone material, the tubular member is also movable in a second position, as shown by <FIG> and <FIG> to misalign the proximal opening of the tubular member with the second opening of the housing to prevent the tubular member from receiving at least the portion of the plunger.

In some embodiments, various orthopedic implants can be used in conjunction with the bone material dispensing device.

In some embodiments, the folding cannula can be made of a memory shape polymer and/or alloy to allow the folding cannula to move from an unfolded configuration to a folded configuration without the need for a locking mechanism. Memory shape polymers include, but are not limited to polyethers, polyacrylates, polyamides, polysiloxanes, polyurethanes, polyethers amides, polyurethane/ureas, polyether esters, polynorborene, cross-linked polymers such as cross-linked polyethylene and cross-linked poly(cyclooctene), inorganic-organic hybrid polymers, and copolymers such as urethane/butadiene copolymers, styrene-butadiene copolymers. Memory shape alloys include, but are not limited to TiNi, CuZnAl, and FeNiAl alloys. In some embodiments, the folding cannula can be fabricated by injection molding of plastic materials comprising rigid, surgical grade plastic and/or metal materials.

In some embodiments, components of the bone material dispensing device may be made from materials, such as for example, polyurethane, polyurea, polyether(amide), PEBA, thermoplastic elastomeric olefin, copolyester, and styrenic thermoplastic elastomer, steel, aluminum, stainless steel, titanium, nitinol, metal alloys with high non-ferrous metal content and a low relative proportion of iron, carbon fiber, glass fiber, plastics, ceramics or combinations thereof. The folding cannula, funnel portion, plunger or tubular member may optionally include one or more tapered regions. In various embodiments, these components may be blunt, beveled, diamond point, ball tip, trocar tip, etc. These components may also have a tip style vital for accurate treatment of the patient depending on the surgical site. Examples of tip styles include, for example, Trephine, Cournand, Veress, Huber, Seldinger, Chiba, Francine, Bias, Crawford, deflected tips, Hustead, Lancet, or Tuohey. In some embodiments, the bone material dispensing device can be made from materials that allow the bone material dispensing device to be reusable, or alternatively made from materials that allow for a single, disposable use.

In some embodiments, the shape of the folding cannula may be selected for particular applications. Such shape and configuration may include, for example, the basic shape of a folding cannula (e.g., a tubular shaped cannula).

A method of loading a bone material dispensing device with the bone material is provided. The method comprising loading a bone material dispensing device (e.g., gun) with the bone material, the bone material dispensing device comprising a housing having a proximal end, a distal end, and a longitudinal axis, the proximal end having a first opening and the distal end having a second opening, the first opening and the second opening configured to slidably receive at least a portion of a plunger; and a tubular member pivotably connected to the housing and configured for lateral movement relative to the longitudinal axis of the housing, the tubular member comprising a proximal opening, a distal opening and a channel disposed therebetween, the proximal opening, the distal opening and the channel of the tubular member configured to receive at least the portion of the plunger, the tubular member being movable in a first position to align the proximal opening of the tubular member with the second opening of the housing to allow the tubular member to receive at least the portion of the plunger to dispense the bone material.

Moving the tubular member in a second position to misalign the proximal opening of the tubular member with the second opening of the housing prevents the tubular member from receiving at least the portion of the plunger.

When the driving handle is pivoted, the driving pawl moves a defined amount. If a translation distance X is multiplied by a diameter of the funnel portion or the cannula, a cylinder of volume can be calculated. The bone material dispensing device can be adjusted to dispense a predefined amount of bone material per pivot of the driving handle. In some embodiments, the predefined amount of bone material dispensed from the bone material dispensing device can be of from about <NUM><NUM> to about <NUM><NUM> or from about <NUM> ounces (oz) to about <NUM> oz.

In some embodiments, the bone material can be dispensed in a quantifiable, controlled and predefined amount of from about <NUM><NUM> to about <NUM><NUM>. The bone material may be dispensed in a quantifiable, controlled and predefined amount of from about <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> to about <NUM><NUM>. In some embodiments, the bone material can be dispensed in a quantifiable, controlled and predefined amount of from about <NUM> oz to about <NUM> oz. The bone material may be dispensed in a quantifiable, controlled and predefined amount of from about <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> to about <NUM> oz.

The bone material can be mixed with liquid material and optionally a therapeutic agent until a desired consistency of the bone material is achieved (e.g., putty, paste, etc.). The bone material can be mixed with a suitable diluent and then loaded. The folding cannula may have enough space to allow for the bone material and a volume of diluent to be mixed. In some embodiments, the diluent includes dextrose, other sugars including but not limited to sucrose, fructose, glucose, lactated ringer's, polyols including but not limited to mannitol, xylitol, sorbitol, maltitol, lactitol, polysaccharides including but not limited to native or pre-gelatinized starch, maltodextrins, cyclodextrins, mineral compounds including but not limited to dicalcium or tricalcium phosphate, either dihydrate or anhydrous, cellulose derivatives including but not limited to microcrystalline cellulose, lactoses either monohydrates thereof or anhydrous, as well as their mixtures such as dicalcium phosphate dihydrate, mannitol, pre-gelatinized maize starch, microcrystalline cellulose and their mixtures, water and/or NaCl (saline). In some embodiments, the saline is <NUM>% saline or <NUM>% saline. In some embodiments, other delivery vehicles can be used for example, D5W (dextrose in <NUM>% water), D5NS (dextrose in <NUM>% water and normal saline) and D5W/<NUM>/2NS (D5Wand ½ normal saline), blood, mesenchymal stem cells, or the like.

In various embodiments, a kit is provided comprising the bone material dispensing device. The kit may include additional parts along with the bone material dispensing device including the bone material and other components to be used to administer the bone material (e.g., wipes, needles, syringes, other mixing devices, etc.). The kit may include the bone material dispensing device in a first compartment. The second compartment may include the bone material. The third compartment may include a tray used for loading the bone material dispensing device with the bone material. In some embodiments, the shape of the tray may be selected for particular applications. Such shape and configuration may include, for example, the basic shape of a tray (e.g., a square shaped box, etc.).

The fourth compartment may include a vial holding the carrier and any other instruments needed for the delivery. A fifth compartment may include gloves, drapes, wound dressings and other procedural supplies for maintaining sterility of the implanting process, as well as an instruction booklet, which may include a chart that shows how to administer the bone material after mixing it. A sixth compartment may include needles, additional devices and/or sutures. Each tool may be separately packaged in a plastic pouch that is sterilized. A seventh compartment may include an agent for radiographic imaging. A cover of the kit may include illustrations of the dispensing/administering procedure and a clear plastic cover may be placed over the compartments to maintain sterility.

In various embodiments, one or more components of the bone material dispensing device is sterilized by radiation in a terminal sterilization step in the final packaging. Terminal sterilization of a product provides greater assurance of sterility than from processes such as an aseptic process, which require individual product components to be sterilized separately and the final package assembled in a sterile environment.

In various embodiments, gamma radiation is used in the terminal sterilization step, which involves utilizing ionizing energy from gamma rays that penetrate deeply into the bone material dispensing device. Gamma rays are highly effective in killing microorganisms, they leave no residues, nor do they have sufficient energy to impart radioactivity to the apparatus. Gamma rays can be employed when the device is in the package and gamma sterilization does not require high pressures or vacuum conditions, thus, package seals and other components are not stressed. In addition, gamma radiation eliminates the need for permeable packaging materials.

In various embodiments, electron beam (e-beam) radiation may be used to sterilize one or more components of the bone material dispensing device. E-beam radiation comprises a form of ionizing energy, which is generally characterized by low penetration and high-dose rates. E-beam irradiation is similar to gamma processing in that it alters various chemical and molecular bonds on contact, including the reproductive cells of microorganisms. Beams produced for e-beam sterilization are concentrated, highly-charged streams of electrons generated by the acceleration and conversion of electricity.

Other methods may also be used to sterilize the bone material dispensing device including, but not limited to, gas sterilization such as, for example, with ethylene oxide or steam sterilization.

The bone material dispensing device can be used to treat a variety of conditions including osteoporosis, bone fracture repair or healing, dental procedures for which increased bone formation in the jaw is of clinical benefit, repair of craniofacial bone defects induced by trauma or congenital defects such as cleft palate/lip, and a number of other musculoskeletal disorders where native bone growth is inadequate, which will be evident to those of ordinary skill in the art. The bone material can be administered to treat open fractures and fractures at high risk of non-union, and in subjects with spinal disorders, including subjects in need of spine fusion (e.g., anterior lumbar interbody fusion, posterior lumbar spinal fusion, and cervical spine fusion) or subjects having degenerative disc disease or arthritis affecting the lumbar and cervical spine.

In some embodiments, the bone material can be demineralized bone material. The demineralized bone material can comprise demineralized bone, powder, chips, granules, shards, fibers or other shapes having irregular or random geometries. These can include, for example, substantially demineralized, partially demineralized, or fully demineralized cortical and cancellous bone. These also include surface demineralization, where the surface of the bone construct is substantially demineralized, partially demineralized, or fully demineralized, yet the body of the bone construct is fully mineralized. The configuration of the bone material can be obtained by milling, shaving, cutting or machining whole bone.

In some embodiments, the bone material can comprise elongated demineralized bone fibers having an average length to average thickness ratio or aspect ratio of the fibers from about <NUM>:<NUM> to about <NUM>:<NUM>. In overall appearance the elongated demineralized bone fibers can be round, spherical, granular, elongated, powders, chips, fibers, cylinders, threads, narrow strips, thin sheets, or a combination thereof. In some embodiments, the bone material comprises elongated demineralized bone fibers and chips. In some embodiments, the bone material comprises fully demineralized fibers and surface demineralized chips. In some embodiments, the ratio of fibers to chips or powders is from about <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, or <NUM> fibers to about <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, or <NUM> chips.

In some embodiments, the bone material comprises demineralized bone matrix fibers and demineralized bone matrix chips in a <NUM>:<NUM> ratio. In some embodiments, the bone material comprises demineralized bone matrix fibers and demineralized bone matrix chips in a ratio of <NUM>:<NUM> to about <NUM>:<NUM> fibers to chips.

In some embodiments, the bone material can be an inorganic material, such as an inorganic ceramic and/or bone substitute material. Exemplary inorganic materials or bone substitute materials include but are not limited to aragonite, dahlite, calcite, brushite, amorphous calcium carbonate, vaterite, weddellite, whewellite, struvite, urate, ferrihydrate, francolite, monohydrocalcite, magnetite, goethite, dentin, calcium carbonate, calcium sulfate, calcium phosphosilicate, sodium phosphate, calcium aluminate, calcium phosphate, hydroxyapatite, alpha-tricalcium phosphate, dicalcium phosphate, β-tricalcium phosphate, tetracalcium phosphate, amorphous calcium phosphate, octacalcium phosphate, BIOGLASS™ fluoroapatite, chlorapatite, magnesium-substituted tricalcium phosphate, carbonate hydroxyapatite, substituted forms of hydroxyapatite (e.g., hydroxyapatite derived from bone may be substituted with other ions such as fluoride, chloride, magnesium sodium, potassium, etc.), or combinations or derivatives thereof.

In some embodiments, the bone material can comprise mineral particles, which comprise tricalcium phosphate and hydroxyapatite in a ratio of about <NUM>:<NUM> to about <NUM>:<NUM>. In some embodiments, the mineral particles can comprise tricalcium phosphate and hydroxyapatite in a ratio of about <NUM>:<NUM> to about <NUM>:<NUM>. In some embodiments, the mineral particles can comprise tricalcium phosphate and hydroxyapatite in a ratio of about <NUM>:<NUM>.

In some embodiments, the bone material may be seeded with harvested bone cells and/or bone tissue, such as for example, cortical bone, autogenous bone, allogenic bones and/or xenogeneic bone while it is mixed.

In some embodiments, the bone material may be mixed with one or more therapeutic agents, for example, an anti-inflammatory agent, an analgesic agent, an osteoinductive growth factor, an antimicrobial agent or a combination thereof. Osteoinductive agents include one or more members of the family of Bone Morphogenetic Proteins ("BMPs"). BMPs are a class of proteins thought to have osteoinductive or growth-promoting activities on endogenous bone tissue, or function as pro-collagen precursors. Known members of the BMP family include, but are not limited to, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM> (GDF-<NUM>), BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM> as well as polynucleotides or polypeptides thereof, as well as mature polypeptides or polynucleotides encoding the same.

BMPs utilized as osteoinductive agents comprise one or more of BMP-<NUM>; BMP-<NUM>; BMP-<NUM>; BMP-<NUM>; BMP-<NUM>; BMP-<NUM>; BMP-<NUM>; BMP-<NUM>; BMP-<NUM>; BMP-<NUM>; BMP-<NUM>; BMP-<NUM>; BMP-<NUM>; BMP-<NUM>; BMP-<NUM>; BMP-<NUM>; or BMP-<NUM>; as well as any combination of one or more of these BMPs, including full length BMPs or fragments thereof, or combinations thereof, either as polypeptides or polynucleotides encoding the polypeptide fragments of all of the recited BMPs. The isolated BMP osteoinductive agents may be administered as polynucleotides, polypeptides, full length protein or combinations thereof.

Indeed, the osteoinductive factors are the recombinant human bone morphogenetic proteins (rhBMPs) because they are available in unlimited supply and do not transmit infectious diseases. In some embodiments, the bone morphogenetic protein is a rhBMP-<NUM>, rhBMP-<NUM>, rhBMP-<NUM>, or heterodimers thereof. Recombinant BMP-<NUM> can be used at a concentration of about <NUM>/mL to about <NUM>/mL, preferably about <NUM>/mL.

The bone material may include or be mixed with one or more members from the TGF-β superfamily. For example, the matrix may include AMH, ARTN, GDF1, GDF10, GDF11, GDF15, GDF2, GDF3, GDF3A, GDF5, GDF6, GDF7, GDF8, GDF9, GDNF, INHA, INHBA, INHBB, INHBC, INHBE, LEFTY1, LEFTY2, MSTN, NODAL, NRTN, PSPN, TGFB1, TGFB2, TGFB3, FGF, basic FGF, VEGF, insulin-like growth factor, EGF, PDGF, nerve growth factor or combinations thereof.

The bone material may include or be mixed with a therapeutic agent including, but not limited to, IL-<NUM> inhibitors, such Kineret® (anakinra), which is a recombinant, non-glycosylated form of the human interleukin-<NUM> receptor antagonist (IL-1Ra), or AMG <NUM>, which is a monoclonal antibody that blocks the action of IL-<NUM>. The bone material may include or be mixed with therapeutic agents including excitatory amino acids such as glutamate and aspartate, antagonists or inhibitors of glutamate binding to NMDA receptors, AMPA receptors, and/or kainate receptors. The bone material may include or be mixed with therapeutic agents to reduce inflammation including but not limited to interleukin-<NUM> receptor antagonists, thalidomide (a TNF-α release inhibitor), thalidomide analogues (which reduce TNF-α production by macrophages), quinapril (an inhibitor of angiotensin II, which upregulates TNF-α), interferons such as IL-<NUM> (which modulate TNF-α receptor expression), or aurin-tricarboxylic acid (which inhibits TNF-α).

The bone material may include or be mixed with a therapeutic agent including, but not limited to, an analgesic agent. Examples of analgesic agents include, but are not limited to, acetaminophen, tramadol, lidocaine, bupivacaine, ropivacaine, opioid analgesics such as buprenorphine, butorphanol, dextromoramide, dezocine, dextropropoxyphene, diamorphine, fentanyl, alfentanil, sufentanil, hydrocodone, hydromorphone, ketobemidone, levomethadyl, levorphanol, meperidine, methadone, morphine, nalbuphine, opium, oxycodone, papaveretum, pentazocine, pethidine, phenoperidine, piritramide, dextropropoxyphene, remifentanil, sufentanil, tilidine, tramadol, codeine, dihydrocodeine, meptazinol, dezocine, eptazocine, flupirtine or a combination thereof.

The bone material may include or be mixed with a therapeutic agent including, but not limited to, an anti-inflammatory agent. An example of an anti-inflammatory agent includes, but is not limited to, clonidine, sulindac, sulfasalazine, naroxyn, diclofenac, indomethacin, ibuprofen, flurbiprofen, ketoprofen, aclofenac, aloxiprin, aproxen, aspirin, diflunisal, fenoprofen, mefenamic acid, naproxen, phenylbutazone, piroxicam, meloxicam, salicylamide, salicylic acid, desoxysulindac, tenoxicam, ketoralac, clonidine, flufenisal, salsalate, triethanolamine salicylate, aminopyrine, antipyrine, oxyphenbutazone, apazone, cintazone, flufenamic acid, clonixeril, clonixin, meclofenamic acid, flunixin, colchicine, demecolcine, allopurinol, oxypurinol, benzydamine hydrochloride, dimefadane, indoxole, intrazole, mimbane hydrochloride, paranylene hydrochloride, tetrydamine, benzindopyrine hydrochloride, fluprofen, ibufenac, naproxol, fenbufen, cinchophen, diflumidone sodium, fenamole, flutiazin, metazamide, letimide hydrochloride, nexeridine hydrochloride, octazamide, molinazole, neocinchophen, nimazole, proxazole citrate, tesicam, tesimide, tolmetin, triflumidate, fenamates (mefenamic acid, meclofenamic acid), nabumetone, celecoxib, etodolac, nimesulide, apazone, gold, tepoxalin; dithiocarbamate, or a combination thereof.

Anti-inflammatory agents also include steroids, such as for example, <NUM>-acetoxypregnenolone, alclometasone, algestone, amcinonide, beclomethasone, betamethasone, budesonide, chloroprednisone, clobetasol, clobetasone, clocortolone, cloprednol, corticosterone, cortisone, cortivazol, deflazacort, desonide, desoximetasone, dexamethasone, dexamethasone <NUM>-acetate, dexamethasone <NUM>-phosphate di-Na salt, diflorasone, diflucortolone, difluprednate, enoxolone, fluazacort, flucloronide, flumethasone, flunisolide, fluocinolone acetonide, fluocinonide, fluocortin butyl, fluocortolone, fluorometholone, fluperolone acetate, fluprednidene acetate, fluprednisolone, flurandrenolide, fluticasone propionate, formocortal, halcinonide, halobetasol propionate, halometasone, halopredone acetate, hydrocortamate, hydrocortisone, loteprednol etabonate, mazipredone, medrysone, meprednisone, methylprednisolone, mometasone furoate, paramethasone, prednicarbate, prednisolone, prednisolone <NUM>-diethylamino-acetate, prednisolone sodium phosphate, prednisone, prednival, prednylidene, rimexolone, tixocortol, triamcinolone, triamcinolone acetonide, triamcinolone benetonide, triamcinolone hexacetonide or a combination thereof.

The bone material may include or be mixed with a therapeutic agent including, but not limited to, a statin. Examples of a useful statin include, but are not limited to, atorvastatin, simvastatin, pravastatin, cerivastatin, mevastatin, velostatin (also called synvinolin;), fluvastatin, lovastatin, rosuvastatin and fluindostatin (Sandoz XU-<NUM>-<NUM>), dalvastain, eptastatin, pitavastatin, or pharmaceutically acceptable salts thereof or a combination thereof. In various embodiments, the statin may comprise mixtures of (+)R and (-)-S enantiomers of the statin. In various embodiments, the statin may comprise a <NUM>:<NUM> racemic mixture of the statin.

In some embodiments, the bone material can include an antimicrobial agent. In some embodiments, the antimicrobial agent can include one or more of triclosan, also known as <NUM>,<NUM>,<NUM>'-trichloro-<NUM>'-hydroxydiphenyl ether, chlorhexidine and its salts, including chlorhexidine acetate, chlorhexidine gluconate, chlorhexidine hydrochloride, and chlorhexidine sulfate, silver and its salts, including silver acetate, silver benzoate, silver carbonate, silver citrate, silver iodate, silver iodide, silver lactate, silver laurate, silver nitrate, silver oxide, silver palmitate, silver protein, and silver sulfadiazine, polymyxin, tetracycline, aminoglycosides, such as tobramycin and gentamicin, rifampicin, bacitracin, neomycin, chloramphenicol, miconazole, quinolones such as oxolinic acid, norfloxacin, nalidixic acid, pefloxacin, enoxacin and ciprofloxacin, penicillins such as oxacillin and pipracil, nonoxynol <NUM>, fusidic acid, cephalosporins, or combinations thereof.

Examples of antimicrobial agents include, by way of illustration and not limited to, acedapsone; acetosulfone sodium; alamecin; alexidine; amdinocillin; amdinocillin pivoxil; amicycline; amifloxacin; amifloxacin mesylate; amikacin; amikacin sulfate; aminosalicylic acid; aminosalicylate sodium; amoxicillin; amphomycin; ampicillin; ampicillin sodium; apalcillin sodium; apramycin; aspartocin; astromicin sulfate; avilamycin; avoparcin; azithromycin; azlocillin; azlocillin sodium; bacampicillin hydrochloride; bacitracin; bacitracin methylene disalicylate; bacitracin zinc; bambermycins; benzoylpas calcium; berythromycin; betamicin sulfate; biapenem; biniramycin; biphenamine hydrochloride; bispyrithione magsulfex; butikacin; butirosin sulfate; capreomycin sulfate; carbadox; carbenicillin disodium; carbenicillin indanyl sodium; carbenicillin phenyl sodium; carbenicillin potassium; carumonam sodium; cefaclor; cefadroxil; cefamandole; cefamandole nafate; cefamandole sodium; cefaparole; cefatrizine; cefazaflur sodium; cefazolin; cefazolin sodium; cefbuperazone; cefdinir; cefepime; cefepime hydrochloride; cefetecol; cefixime; cefmenoxime hydrochloride; cefmetazole; cefmetazole sodium; cefonicid monosodium; cefonicid sodium; cefoperazone sodium; ceforanide; cefotaxime sodium; cefotetan; cefotetan disodium; cefotiam hydrochloride; cefoxitin; cefoxitin sodium; cefpimizole; cefpimizole sodium; cefpiramide; cefpiramide sodium; cefpirome sulfate; cefpodoxime proxetil; cefprozil; cefroxadine; cefsulodin sodium; ceftazidime; ceftibuten; ceftizoxime sodium; ceftriaxone sodium; cefuroxime; cefuroxime axetil; cefuroxime pivoxetil; cefuroxime sodium; cephacetrile sodium; cephalexin; cephalexin hydrochloride; cephaloglycin; cephaloridine; cephalothin sodium; cephapirin sodium; cephradine; cetocycline hydrochloride; cetophenicol; chloramphenicol; chloramphenicol palmitate; chloramphenicol pantothenate complex; chloramphenicol sodium succinate; chlorhexidine phosphanilate; chloroxylenol; chlortetracycline bisulfate; chlortetracycline hydrochloride; cinoxacin; ciprofloxacin; ciprofloxacin hydrochloride; cirolemycin; clarithromycin; clinafloxacin hydrochloride; clindamycin; clindamycin hydrochloride; clindamycin palmitate hydrochloride; clindamycin phosphate; clofazimine; cloxacillin benzathine; cloxacillin sodium; chlorhexidine, cloxyquin; colistimethate sodium; colistin sulfate; coumermycin; coumermycin sodium; cyclacillin; cycloserine; dalfopristin; dapsone; daptomycin; demeclocycline; demeclocycline hydrochloride; demecycline; denofungin; diaveridine; dicloxacillin; dicloxacillin sodium; dihydrostreptomycin sulfate; dipyrithione; dirithromycin; doxycycline; doxycycline calcium; doxycycline fosfatex; doxycycline hyclate; droxacin sodium; enoxacin; epicillin; epitetracycline hydrochloride; erythromycin; erythromycin acistrate; erythromycin estolate; erythromycin ethylsuccinate; erythromycin gluceptate; erythromycin lactobionate; erythromycin propionate; erythromycin stearate; ethambutol hydrochloride; ethionamide; fleroxacin; floxacillin; fludalanine; flumequine; fosfomycin; fosfomycin tromethamine; fumoxicillin; furazolium chloride; furazolium tartrate; fusidate sodium; fusidic acid; ganciclovir and ganciclovir sodium; gentamicin sulfate; gloximonam; gramicidin; haloprogin; hetacillin; hetacillin potassium; hexedine; ibafloxacin; imipenem; isoconazole; isepamicin; isoniazid; josamycin; kanamycin sulfate; kitasamycin; levofuraltadone; levopropylcillin potassium; lexithromycin; lincomycin; lincomycin hydrochloride; lomefloxacin; lomefloxacin hydrochloride; lomefloxacin mesylate; loracarbef; mafenide; meclocycline; meclocycline sulfosalicylate; megalomicin potassium phosphate; mequidox; meropenem; methacycline; methacycline hydrochloride; methenamine; methenamine hippurate; methenamine mandelate; methicillin sodium; metioprim; metronidazole hydrochloride; metronidazole phosphate; mezlocillin; mezlocillin sodium; minocycline; minocycline hydrochloride; mirincamycin hydrochloride; monensin; monensin sodiumr; nafcillin sodium; nalidixate sodium; nalidixic acid; natainycin; nebramycin; neomycin palmitate; neomycin sulfate; neomycin undecylenate; netilmicin sulfate; neutramycin; nifuiradene; nifuraldezone; nifuratel; nifuratrone; nifurdazil; nifurimide; nifiupirinol; nifurquinazol; nifurthiazole; nitrocycline; nitrofurantoin; nitromide; norfloxacin; novobiocin sodium; ofloxacin; onnetoprim; oxacillin and oxacillin sodium; oximonam; oximonam sodium; oxolinic acid; oxytetracycline; oxytetracycline calcium; oxytetracycline hydrochloride; paldimycin; parachlorophenol; paulomycin; pefloxacin; pefloxacin mesylate; penamecillin; penicillins such as penicillin g benzathine, penicillin g potassium, penicillin g procaine, penicillin g sodium, penicillin v, penicillin v benzathine, penicillin v hydrabamine, and penicillin v potassium; pentizidone sodium; phenyl aminosalicylate; piperacillin sodium; pirbenicillin sodium; piridicillin sodium; pirlimycin hydrochloride; pivampicillin hydrochloride; pivampicillin pamoate; pivampicillin probenate; polymyxin b sulfate; porfiromycin; propikacin; pyrazinamide; pyrithione zinc; quindecamine acetate; quinupristin; racephenicol; ramoplanin; ranimycin; relomycin; repromicin; rifabutin; rifametane; rifamexil; rifamide; rifampin; rifapentine; rifaximin; rolitetracycline; rolitetracycline nitrate; rosaramicin; rosaramicin butyrate; rosaramicin propionate; rosaramicin sodium phosphate; rosaramicin stearate; rosoxacin; roxarsone; roxithromycin; sancycline; sanfetrinem sodium; sarmoxicillin; sarpicillin; scopafungin; sisomicin; sisomicin sulfate; sparfloxacin; spectinomycin hydrochloride; spiramycin; stallimycin hydrochloride; steffimycin; streptomycin sulfate; streptonicozid; sulfabenz; sulfabenzamide; sulfacetamide; sulfacetamide sodium; sulfacytine; sulfadiazine; sulfadiazine sodium; sulfadoxine; sulfalene; sulfamerazine; sulfameter; sulfamethazine; sulfamethizole; sulfamethoxazole; sulfamonomethoxine; sulfamoxole; sulfanilate zinc; sulfanitran; sulfasalazine; sulfasomizole; sulfathiazole; sulfazamet; sulfisoxazole; sulfisoxazole acetyl; sulfisboxazole diolamine; sulfomyxin; sulopenem; sultamricillin; suncillin sodium; talampicillin hydrochloride; teicoplanin; temafloxacin hydrochloride; temocillin; tetracycline; tetracycline hydrochloride; tetracycline phosphate complex; tetroxoprim; thiamphenicol; thiphencillin potassium; ticarcillin cresyl sodium; ticarcillin disodium; ticarcillin monosodium; ticlatone; tiodonium chloride; tobramycin; tobramycin sulfate; tosufloxacin; trimethoprim; trimethoprim sulfate; trisulfapyrimidines; troleandomycin; trospectomycin sulfate; tyrothricin; vancomycin; vancomycin hydrochloride; virginiamycin; zorbamycin; or combinations thereof.

The antimicrobial agent in the bone material can be an antiviral agent that can be mixed with the bone material. Antiviral agents can include, but are not limited to, vidarabine, acyclovir, famciclovir, valacyclovir, gancyclovir, valganciclovir, nucleoside-analog reverse transcriptase inhibitors (such as AZT (zidovudine), ddI (didanosine), ddC (zalcitabine), d4T (stavudine), and 3TC (lamivudine)), nevirapine, delavirdine, protease inhibitors (such as, saquinavir, ritonavir, indinavir, and nelfinavir), ribavirin, amantadine, rimantadine, neuraminidase inhibitors (such as zanamivir and oseltamivir), pleconaril, cidofovir, foscarnet, and/or interferons.

Claim 1:
A bone material dispensing device (<NUM>) comprising a housing (<NUM>) having a proximal end (<NUM>), a distal end (<NUM>), and a longitudinal axis (AA), the proximal end (<NUM>) having a first opening (<NUM>) and the distal end (<NUM>) having a second opening (<NUM>), the first opening (<NUM>) and the second opening (<NUM>) configured to slidably receive at least a portion of a plunger (<NUM>); and a tubular member (<NUM>) pivotably connected to the housing (<NUM>) and configured for lateral movement relative to the longitudinal axis (AA) of the housing (<NUM>), the tubular member (<NUM>) comprising a proximal opening (<NUM>), a distal opening (<NUM>) and a channel (<NUM>) disposed therebetween for disposal of bone material, the proximal opening (<NUM>), the distal opening (<NUM>) and the channel (<NUM>) of the tubular member (<NUM>) configured to receive at least the portion of the plunger (<NUM>), wherein the tubular member (<NUM>) is pivotably connected to the housing (<NUM>) via a pivot point (<NUM>) transverse relative to the longitudinal axis (AA), wherein the tubular member (<NUM>) is configured for lateral movement relative to the longitudinal axis (AA) of the housing (<NUM>) via the pivot point (<NUM>), so that the tubular member (<NUM>) is movable in a first position to align the proximal opening (<NUM>) of the tubular member (<NUM>) with the second opening (<NUM>) of the housing (<NUM>) to allow the tubular member (<NUM>) to receive at least the portion of the plunger (<NUM>) to dispense the bone material,
characterized in that the tubular member (<NUM>) is movable in a second position to misalign the proximal opening (<NUM>) of the tubular member (<NUM>) with the second opening (<NUM>) of the housing (<NUM>) to prevent the tubular member (<NUM>) from receiving at least the portion of the plunger (<NUM>) and thereby to allow the tubular member (<NUM>) to be loaded with bone material.