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.
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.
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.
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.
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,
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.
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.
In one embodiment, the polymer adhesive film 700 may be formed by forming a polymer layer 702. Next, micro-tubes 506a 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 506a in the same direction. A second layer of perpendicular directionally oriented polymer and micro-tubes 506b 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 506a, 506b.
The micro-ridges 806 may be formed in various geometric or irregular shapes. As shown in
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.
The micro-troughs 1106 may be formed in various geometric shapes or irregular shapes. As shown in
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.
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.
Number | Date | Country | |
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61238019 | Aug 2009 | US |