Patent Publication Number: US-2011052646-A1

Title: Polymer adhesive film for directed cellular growth

Description:
FIELD OF THE INVENTION 
     Embodiments described herein relate generally to a polymer adhesive film for use in closing wounds, and more particularly, to a polymer adhesive film including micro-patterns to direct cellular growth to facilitate rapid wound healing. 
     BACKGROUND OF THE INVENTION 
     To prevent infection and promote healing, it is a common practice to close a wound with sutures and protect the surrounding damaged tissues with a dressing or other covering. For example, healing of oral tissue after oral surgery (i.e., surgical tooth extraction) may be hindered by normal masticatory action, tongue movements during speech, and salivary fluid flow. Additionally, debris from food deposits can delay the clotting cascade or disrupt an established clot, and thus, interfere with and delay healing. Therefore, after oral surgery, the surgical incision is typically sutured to attain primary closure of the wound in order to promote healing. However, suturing techniques can be cumbersome, are time consuming, and require a high degree of skill to perform correctly. Furthermore, sutures may not have the necessary strength to hold a wound closed, particularly in the mouth where the wound may be disturbed by the normal functional processes described above. An additional drawback to the use of sutures is that the patient often needs to have them removed at a later date. 
     In addition to sutures, a dressing, such as gauze or a periodontal pack is commonly placed on the surgical site. The dressing may be applied to direct pressure to the wound in order to help stop bleeding, protect against contaminants, and act as a temporary physical barrier to the oral environment. However, a dressing made of an absorbent material, such as cotton, has a limited ability to prevent moisture and saliva from reaching the surgical site in that it may become saturated. Such a dressing is usually only effective for a few hours after surgery. Dressings used on wounds inside and outside of the oral environment suffer from additional drawbacks, such as: need for frequent removal and changing; difficult to attain adhesion of the dressing to the wound; inadequate mechanical properties; and difficult application. 
     It may also be desirable to apply a therapeutic formulation at the wound or surgical site to promote healing. However, topical formulations applied directly or integrated with commonly used dressings are quickly lost due to moisture and mechanical action, and additionally, these formulations are not capable of penetrating skin or mucous membranes. If used in combination with a dressing, therapeutic formulations have several other drawbacks including lack of biodegradability, damage or irritation to the skin during removal of the dressing, covalent bonding or other interaction of the therapeutic agent and the dressing, inability to use a wide variety of therapeutic agents, and inadequate adhesion of the dressing. 
     What is needed is a sterile polymer adhesive film that could: eliminate the need for suturing a wound or surgical site, adequately seal a surgical site or wound from the environment to prevent moisture or debris from reaching the site, optionally provide a therapeutic formulation to the site, be biodegradable to eliminate the need to remove the film, and promote directional cellular growth to securely heal the wound. 
     BRIEF SUMMARY OF THE INVENTION 
     The described embodiments relate to a polymer adhesive film having a micro-pattern arranged on a first surface of the polymer adhesive film for application to wounded tissue to promote directional cell growth. The micro-pattern is sized to allow cells of the wounded tissue to grow directionally in one or two directions within the micro-pattern to promote rapid and efficient healing. In various embodiments, the micro-pattern may be formed of micro-tubes, micro-ridges, micro-troughs, or combinations thereof. 
     The polymer adhesive film may be applied to surgical sites or other wounds to close the wounds and/or cover damaged tissue. The polymer adhesive film may be formulated to adhere to wet tissues such as oral tissues or internal tissues and may be water-proof to prevent water or debris from entering the wound. Furthermore, the polymer adhesive film may be biodegradable to prevent the need to remove the film. The polymer adhesive film may include a therapeutic formulation or pharmaceutical drug to be released over time at the wound or surgical site to promote healing. The polymer adhesive film may be particularly useful for, but is not limited to, closing a surgical site in oral tissue after oral surgical procedures, such as tooth extraction or dental implant insertion. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  illustrates a plan view of an embodiment of a polymer adhesive film described herein. 
         FIG. 2  illustrates a plan view of a second embodiment of a polymer adhesive film described herein. 
         FIG. 3  illustrates a plan view of a third embodiment of a polymer adhesive film described herein. 
         FIG. 4  illustrates a perspective view of a portion of the third embodiment of the polymer adhesive film described herein. 
         FIG. 5  illustrates a cut-away side view of a fourth embodiment of a polymer adhesive film described herein. 
         FIG. 6  illustrates a cut-away side view of a fifth embodiment of a polymer adhesive film described herein. 
         FIG. 7  illustrates a cut-away side view of a sixth embodiment of a polymer adhesive film described herein. 
         FIG. 8  illustrates a cut-away side view of a seventh embodiment of a polymer adhesive film described herein. 
         FIG. 9  illustrates a cut-away side view of an eighth embodiment of a polymer adhesive film described herein. 
         FIG. 10  illustrates a cut-away side view of a ninth embodiment of a polymer adhesive film described herein. 
         FIG. 11  illustrates a cut-away side view of a tenth embodiment of a polymer adhesive film described herein. 
         FIG. 12  illustrates a cut-away side view of an eleventh embodiment of a polymer adhesive film described herein. 
         FIG. 13  illustrates a cut-away side view of a twelfth embodiment of a polymer adhesive film described herein. 
         FIG. 14  illustrates a plan view of a thirteenth embodiment of a polymer adhesive film described herein. 
         FIG. 15  illustrates a plan view of a fourteenth embodiment of a polymer adhesive film described herein. 
         FIG. 16  illustrates a perspective view of a portion of a fifteenth embodiment of a polymer adhesive film described herein. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Surgical incisions and other wounds may heal by primary intention or secondary intention. In healing by primary intention, all tissues are brought together and held in place by mechanical means. In contrast, healing by secondary intention occurs when the margins of the wound are not completely approximated (closed), leaving the wound partially open; yet, the wound still heals, albeit through a distinctly different, much slower process (ie. healing from the “bottom up”). Healing by primary intention is preferable to healing by secondary intention because it minimizes the risk of infection, reduces scar tissue formation, minimizes discomfort during healing, and enables faster healing. The polymer adhesive film embodiments described herein may be used to hold together the ends of wounds in various tissues to facilitate healing by primary intention, while the micro-pattern arranged on a first surface of the polymer adhesive film promotes directional cell growth. 
     Additionally, the polymer adhesive films describe herein are especially advantageous for use in closing surgical sites or wounds in which the edges of the site may not be brought together, for example, in the case of a tooth extraction in which the gap is too large to be completely closed. In this case, the micro-pattern in the polymer adhesive film may promote directional cell growth across the top of the site so that the site behaves as if it were undergoing primary intention, even though all tissues in the site may not be brought together. Thus, the site will heal from the top down and from the bottom up to facilitate faster healing. 
     Example embodiments are now described with reference to the accompanying figures wherein like reference numbers are used consistently for like features throughout the drawings.  FIG. 1  shows a plan view of an embodiment of a polymer adhesive film  100 . The polymer adhesive film  100  includes a micro-patterned portion  104  and non-patterned portions  102  arranged on one side of the polymer adhesive film  100 . In use, the micro-patterned portion  104  will be arranged directly on a surgical site or wound and the non-patterned portions  102  will be arranged on either side of the site. As described below in greater detail, the micro-patterns of the micro-patterned portion  104  are arranged to facilitate directional cellular growth along the micro-patterns to heal wounds more quickly. 
     The polymer adhesive film  100  may be formed of a polymer suitable for use with the specific tissue to which the film  100  is to be applied. For example, the polymer may include various combinations of features such as biocompatibility and biodegradability, mechanical compliance with the specific tissue it is to be used with, strong adhesion under wet or dry conditions as appropriate, elicitation of a minimal inflammatory response, and the ability to deliver therapeutic or pharmaceutical drug formulations. The polymer adhesive film may be formulated from polymers known to adhere to wet tissues, such as oral or internal mucosal tissues, and may be water-proof to prevent water or debris from entering the wound. 
     In one embodiment, the polymer used to form the polymer adhesive film  100  may include a biodegradable condensation polymer of glycerol and a diacid, such as those described in U.S. Patent Application Publication No. 2003/0118692, the disclosure of which is hereby incorporated by reference in its entirety. For example, the polymer adhesive film  100  may be made up of poly(glycerol sebacate), poly(glycerol sebacate)-acrylate having low acrylation, poly(glycerol sebacate)-acrylate having high acrylation, poly(glycerol sebacate)-acrylate-co-poly(ethylene glycol) networks, poly(glycerol malonate), poly(glycerol succinate), poly(glycerol glutarate), poly(glycerol adipate), poly(glycerol pimelate), poly(glycerol suberate), poly(glycerol azelate), polymers of glycerol and diacids having more than 10, more than 15, more than 20, and more than 25 carbon atoms, polymers of glycerol and non-aliphatic diacids, and mixtures thereof. In various embodiments, amines and aromatic groups, such as terephthalic acid and carboxyphenoxypropane may be incorporated into the carbon chain. The diacids may also include substituents as well, such as amine and hydroxyl, to increase the number of sites available for cross-linking, amino acids and other biomolecules to modify the biological properties of the polymer, and aromatic groups, aliphatic groups, and halogen atoms to modify the inter-chain interactions within the polymer. 
     The polymer may further include a biomolecule, a hydrophilic group, a hydrophobic group, a non-protein organic group, an acid, a small molecule, a bioactive agent, a controlled-release therapeutic agent or pharmaceutical drug, or a combination thereof. The polymer may be seeded with cells compatible with the tissue that the polymer adhesive film  100  is designed to cover to facilitate rapid healing. 
     The polymer adhesive film  100  may be coated, for example, by spin coating, with a thin layer of oxidized dextran having aldehyde functionalities (DXTA) to promote covalent cross linking with tissue to which the polymer adhesive film  100  is applied. The terminal aldehyde groups in DXTA react with resident amine groups in proteins forming an imine, while the aldehyde groups of DXTA form a hemiacetal with free hydroxyl groups from a glycerol subunit of the polymer adhesive film  100  surface. The use of DXTA is especially useful to increase the adhesion of the polymer adhesive film  100  to tissue in a wet environment, such as an oral cavity or on internal tissues. 
     The relative widths of the micro-patterned portion  104  and non-patterned portions  102  may be adjusted to various lengths on of the polymer adhesive film  100  depending on the intended use of the film  100 . For example,  FIG. 2  shows a plan view of a second embodiment of a polymer adhesive film  200  in which the micro-patterned portion  204  extends over the entire surface of the polymer adhesive film  200 . Furthermore, the dimensions of the polymer adhesive films  100 ,  200  may be modified as needed for a particular application. For example, the overall thickness of the polymer adhesive films of the various embodiments described herein may be adjusted to strike an appropriate balance between the strength and flexibility of the film. 
       FIG. 3  shows a plan view of a third embodiment of a polymer adhesive film  300  that includes a micro-patterned portion  304  for promoting directional cellular growth and a nano-patterned portion  306  for increasing the adhesion of the polymer adhesive film  300  to the tissue.  FIG. 4  shows a perspective view of a portion of the nano-patterned portion  306 . As shown in  FIG. 4 , the nano-patterned portion  306  includes an array of pillars  408  arranged on the surface of the nano-patterned portion  306  of the polymer adhesive film  300 . The pillars  408  increase the adhesion of the polymer adhesive film  300  to the tissue by allowing the film  300  to conform and adhere to the uneven surface of the tissue, thus maximizing interfacial contact to enhance adhesion. 
     A mold used to produce the pillars  408  of the nano-patterned portion  306  may be prepared by patterning a silicon substrate using a combination of photolithography and reactive ion etching to generate the mold. The pillars  408  may then be formed by casting the polymer adhesive film  300  onto the mold and curing the adhesive film  300 , for example using ultraviolet light or heat, as appropriate to the particular polymer. The dimensions of the pillars  408 , including the tip width w, height h, and pitch p, may vary according to the tissue to which the polymer adhesive film  300  is to be affixed. In one embodiment, the pillars  408  may include tip widths w ranging from about 100 nm to about 1 μm and pillar heights h from about 0.8 μm to about 3 μm. The nano-patterned portion  306  may be coated with a layer of DXTA, as described above, to further improve the adhesion properties of the polymer adhesive film  300 . 
       FIG. 5  shows a cut-away side view of a fourth embodiment of a polymer adhesive film  500  made up of a polymer layer  502  and a micro-patterned portion  504  made up of micro-tubes  506  arranged on one side of the polymer layer  502 . The micro-patterned portion  504  of the adhesive film  500  may be incorporated as the micro-patterned portion  104 ,  204 ,  304  of the polymer adhesive films  100 ,  200 ,  300  shown in the embodiments of  FIGS. 1-3 , respectively. As shown in  FIG. 5 , the micro-tubes  506  may be closely packed so that the cells of the tissue to be repaired will grow directionally through the micro-tubes  506 . When the biodegradable polymer adhesive film  500  disintegrates, the cells will fill the gaps left by the film  500  to complete the healing process. 
     The micro-tubes  506  may be carbon micro-tubes or any other type of micro-tubes, which are commercially available and preferably purified, for example, single wall micro- or nano-tubes, multi-wall micro- or nano-tubes, bamboo micro- or nano-tubes, and the like. The micro-tubes  506  may be formed of carbon or other materials, which may be biodegradable. 
     The diameter D of the micro-tubes  506  may be sized to accommodate the type of cells surrounding the wound or site to which the polymer adhesive film  500  will be affixed. The diameter D of the micro-tubes  506  may be as small as the size of at least one biological cell or at least one cell process or may be sized to accommodate the combined size of a group of cells. In various embodiments, the diameter D of the micro-tubes  506  may be between about 0.5 μm to about 100 μm, larger than 100 μm, or between about 10 μm to about 40 μm. The length of the micro-tubes  506  may vary as well, according to the desired application. In various embodiments, the micro-tubes  506  may stretch all the way across a micro-patterned area  104 ,  204 ,  304 . In other embodiments, the micro-tubes  506  may be shorter than the width of the micro-patterned area  104 ,  204 ,  304 , and may overlap each other. 
     In one embodiment, the polymer adhesive film  500  may be formed by forming a polymer layer  502 , for example, by casting or extrusion. Next, micro-tubes  506  may be applied to the polymer layer  502  while the polymer layer  502  is in a semi-solid phase, for example, by rolling, spraying, or immersion. The polymer layer  502  may then be rubbed or combed in one direction to align the polymer molecules in the same direction. Physical contact of the polymer molecules with the micro-tubes  506  aligns the micro-tubes  506  in generally the same direction. The polymer layer  502  may then be cured, for example, by ultraviolet light or heating, to lock in the direction of the micro-tubes  506 . An additional step of etching back the polymer layer  502  may also be performed to expose larger portions of the micro-tubes  506  so that cells may more easily grow through the tubes. 
       FIG. 6  shows a cut-away side view of a fifth embodiment of a polymer adhesive film  600  made up of a polymer layer  602  and a micro-patterned portion  604  made up of micro-tubes  506  arranged on one side of the polymer layer  602 . The polymer adhesive film  600  is similar to the polymer adhesive film  500  of  FIG. 5 , except that the micro-tubes  506  of polymer adhesive film  600  may be spaced apart so that the cells of the tissue to be repaired will grow directionally both through and between the micro-tubes  506 . When the biodegradable polymer adhesive film  600  disintegrates, the cells will fill the gaps left by the film  600  to complete the healing process. 
       FIG. 7  shows a cut-away side view of a sixth embodiment of a polymer adhesive film  700  made up of a polymer layer  702  and a micro-patterned portion  704  made up of micro-tubes  506   a ,  506   b  arranged on one side of the polymer layer  702 . The polymer adhesive film  700  is similar to the polymer adhesive film  500  of  FIG. 5 , except that the micro-tubes  506   a ,  506   b  include a first layer of micro-tubes  506   a  arranged in a first direction, and a second layer of micro-tubes  506   b  arranged in a second direction perpendicular to the first direction. The perpendicular micro-tubes  506   a ,  506   b  will facilitate directional cellular growth in two directions. When the biodegradable polymer adhesive film  700  disintegrates, the cells will fill the gaps left by the film  700  to complete the healing process. 
     In one embodiment, the polymer adhesive film  700  may be formed by forming a polymer layer  702 . Next, micro-tubes  506   a  may be applied to the polymer layer  702  while the polymer layer  702  is in a semi-solid phase. The polymer layer  702  may then be rubbed or combed in one direction to align the polymer molecules and micro-tubes  506   a  in the same direction. A second layer of perpendicular directionally oriented polymer and micro-tubes  506   b  may be overlaid on the first polymer layer  702 . The polymer layer  702  may then be cured, and etching back the polymer layer  702  may be performed to expose larger portions of the micro-tubes  506   a ,  506   b.    
       FIG. 8  shows a cut-away side view of a seventh embodiment of a polymer adhesive film  800  made up of a polymer layer  802  and a micro-patterned portion  804  made up of micro-ridges  806  arranged on one side of the polymer layer  802 . The micro-patterned portion  804  of the adhesive film  800  may be incorporated as the micro-patterned portion  104 ,  204 ,  304  of the polymer adhesive films  100 ,  200 ,  300  shown in the embodiments of  FIGS. 1-3 , respectively. The micro-ridges  806  are arranged parallel to each other and may extend the length of the micro-patterned portion  104 ,  204 ,  304 . When the polymer adhesive film  800  is applied to a wound or surgery site, the micro-ridges  806  will direct the cell growth between the micro-ridges  806  and across (perpendicular to) the wound or surgical site. When the biodegradable polymer adhesive film  800  disintegrates, the cells will fill the gaps left by the film  800  to complete the healing process. 
     The micro-ridges  806  may be formed in various geometric or irregular shapes. As shown in  FIG. 8 , the micro-ridges  806  may have a cross-section shaped as half circles extending from the polymer layer  802 .  FIG. 9  shows a cut-away side view of an eighth embodiment of a polymer adhesive film  900  made up of a polymer layer  902  and a micro-patterned portion  904  made up of micro-ridges  906  having a cross-sectional shape of a rectangle.  FIG. 10  shows a cut-away side view of a ninth embodiment of a polymer adhesive film  1000  made up of a polymer layer  1002  and a micro-patterned portion  1004  made up of micro-ridges  1006  having a cross-sectional shape of a triangle. In various other embodiments, the micro-ridges may have other cross-sectional shapes, such as partial ovals, arcs, trapezoids, squares, irregular polyhedrals, and combinations thereof. 
     The width of the spacing S between the micro-ridges  806 ,  906 ,  1006  may be sized to accommodate the type of cells surrounding the wound or site to which the polymer adhesive film  800 ,  900 ,  1000  will be affixed. The spacing S between the micro-ridges  806 ,  906 ,  1006  may be as small as the size of at least one biological cell or at least one cell process or may be sized to accommodate the combined size of a group of cells. In various embodiments, the spacing S between the micro-ridges  806 ,  906 ,  1006  may be between about 0.5 μm to about 100 μm, larger than 100 μm, or between about 10 μm to about 40 μm. The width W and height H of the micro-ridges  806 ,  906 ,  1006  may be varied depending on the application. 
     In one embodiment, the polymer adhesive films  800 ,  900 ,  1000  may be formed by forming a polymer layer  802 ,  902 ,  1002 , for example, by casting or extrusion. Next, micro-ridges  806 ,  906 ,  1006  may be formed on the polymer layer  802 ,  902 ,  1002  while the polymer layer  802 ,  902 ,  1002  is in a semi-solid phase, for example, by applying a negative micro-mold to the polymer layer  802 ,  902 ,  1002 . The polymer layer  802 ,  902 ,  1002  may then be cured, for example, by ultraviolet light or heating. In various embodiments, the micro-ridges  806 ,  906 ,  1006  may be formed by other methods, for example, by a photoresist and etching process. 
       FIG. 11  shows a cut-away side view of a tenth embodiment of a polymer adhesive film  1100  made up of a polymer layer  1102  and a micro-patterned portion  1104  made up of micro-troughs  1106  arranged on one side of the polymer layer  1102 . The micro-patterned portion  1104  of the adhesive film  1100  may be incorporated as the micro-patterned portion  104 ,  204 ,  304  of the polymer adhesive films  130 ,  200 ,  300  shown in the embodiments of  FIGS. 1-3 , respectively. The micro-troughs  1106  are arranged parallel to each other and may extend the length of the micro-patterned portion  104 ,  204 ,  304 . When the polymer adhesive film  1100  is applied to a wound or surgery site, the micro-troughs  1106  will direct the cell growth between the micro-troughs  1106  and across (perpendicular to) the wound or surgical site. When the biodegradable polymer adhesive film  1100  disintegrates, the cells will fill the gaps left by the film  1100  to complete the healing process. 
     The micro-troughs  1106  may be formed in various geometric shapes or irregular shapes. As shown in  FIG. 11 , the micro-troughs  1106  may have a cross-section shaped as half circles extending into the polymer layer  1102 .  FIG. 12  shows a cut-away side view of an eleventh embodiment of a polymer adhesive film  1200  made up of a polymer layer  1202  and a micro-patterned portion  1204  made up of micro-troughs  1206  having a cross-sectional shape of a rectangle.  FIG. 13  shows a cut-away side view of a twelfth embodiment of a polymer adhesive film  1300  made up of a polymer layer  1302  and a micro-patterned portion  1304  made up of micro-troughs  1306  having a cross-sectional shape of a triangle. In various other embodiments, the micro-troughs may have other cross-sectional shapes, such as partial ovals, arcs, trapezoids, squares, irregular polyhedrals, and combinations thereof. 
     The width W of the micro-troughs  1106 ,  1206 ,  1306  may be sized to accommodate the type of cells surrounding the wound or site to which the polymer adhesive film  1100 ,  1200 ,  1300  will be affixed. The width W of the micro-troughs  1106 ,  1206 ,  1306  may be as small as the size of at least one biological cell or at least one cell process or may be sized to accommodate the combined size of a group of cells. In various embodiments, the width W between the micro-troughs  1106 ,  1206 ,  1306  may be between about 0.5 μm to about 130 μm, larger than 130 μm, or between about 13 μm to about 40 μm. The spacing S between and height H of the micro-troughs  1106 ,  1206 ,  1306  may be varied depending on the application. 
     In one embodiment, the polymer adhesive films  1100 ,  1200 ,  1300  may be formed by forming a polymer layer  1102 ,  1202 ,  1302 , for example, by casting or extrusion. Next, micro-troughs  1106 ,  1206 ,  1306  may be formed on the polymer layer  1102 ,  1202 ,  1302  while the polymer layer  1102 ,  1202 ,  1302  is in a semi-solid phase, for example, by applying a positive micro-mold to the polymer layer  1102 ,  1202 ,  1302 . The polymer layer  1102 ,  1202 ,  1302  may then be cured, for example, by ultraviolet light or heating. In various embodiments, the micro-troughs  1106 ,  1206 ,  1306  may be formed by other methods, for example, by a photoresist and etching process. 
       FIG. 14  shows a plan view of a thirteenth embodiment of a polymer adhesive film  1400  including a number of micro-features  1406  arranged parallel to each other on a polymer layer  1402 . The micro-features  1406  may be the micro-ridges  806 ,  906 ,  1006 , or the micro-troughs  1106 ,  1206 ,  1306  shown in  FIGS. 8-13 , respectively. Although the micro-features  1406  of the embodiment of  FIG. 14  are shown as having straight sides, in various embodiments, the micro-features could be wavy, jagged, or otherwise shaped. 
       FIG. 15  shows a plan view of a fourteenth embodiment of a polymer adhesive film  1500  including a number of first micro-features  1506  intersecting a number of second micro-features  1506   b  arranged on a polymer layer  1502 . The first micro-features  1506   a  are arranged parallel to each other and perpendicular to the second micro-features  1506   b . The micro-features  1506   a ,  1506   b  may be the micro-troughs  1106 ,  1206 ,  1306  shown in  FIGS. 11-13 , respectively. The perpendicular micro-features  1506   a ,  1506   b  allow for bi-directional cellular growth both perpendicular and parallel to the wound or surgery site to which the polymer adhesive film  1500  is applied. 
       FIG. 16  shows a perspective view of a fifteenth embodiment of a polymer adhesive film  1600  made up of a polymer layer  1602  and a micro-patterned portion  1604  made up of a combination of micro-ridges  1606  and nano-patterned pillars  1608  arranged on one side of the polymer layer  1602 . The micro-patterned portion  1604  of the adhesive film  1600  may be incorporated as the micro-patterned portion  104 ,  204 ,  304  of the polymer adhesive films  100 ,  200 ,  300  shown in the embodiments of  FIGS. 1-3 , respectively. The micro-ridges  1606  are arranged parallel to each other and may extend the length of the micro-patterned portion  104 ,  204 ,  304 . The micro-ridges  1606  may be formed in various geometric shapes or irregular shapes, and may be shaped and spaced as the micro-ridges  806 ,  906 ,  1006  described in  FIGS. 8 ,  9 , and  10 , respectively. The pillars  1608  formed as a portion of, or all of, the pillars  408  described in  FIG. 4 . 
     When the polymer adhesive film  1600  is applied to a wound or surgery site, the micro-ridges  1606  will direct the cells in directional cellular growth between the micro-ridges  1606  and across, i.e., perpendicular to, the wound or surgery site while the nano-patterned pillars  1608  will increase the adhesion of the polymer adhesive film  1600  to the wound or surgery incision site. When the biodegradable polymer adhesive film  1600  disintegrates, the cells will fill the gaps left by the film  1600  to complete the healing process. 
     In one embodiment, the polymer adhesive film  1600  may be formed by forming a polymer layer  1602 , for example, by casting or extrusion. Next, micro-ridges  1606  and pillars  1608  may be formed on the polymer layer  1602  while the polymer layer  1602  is in a semi-solid phase, for example, by applying a negative micro-mold to the polymer layer  1602 . The polymer layer  1602 , may then be cured, for example, by ultraviolet light or heating. 
     Changes and modifications in the specifically described embodiments and methods can be carried out without departing from the scope of the invention which is intended to be limited only by the scope of the appended claims. For example, although the prefixes “micro-” and “nano-” are used in various places throughout the specification and claims, it should be understood that in various embodiments, micro-features could be formed at a nano-scale and vice-versa. Furthermore, it is contemplated that features of the various embodiments could be combined in certain embodiments.