Advanced Micro-patterned Wound Dressings for Enhanced Epithelialization

描述（由申请人提供）：美国急诊科每年治疗近1200万伤口。皮肤伤口，如严重烧伤，大创伤伤口，或未愈合/慢性伤口太广泛或复杂，无法自然愈合，通常使用自体皮肤移植物重建。虽然自体皮肤移植目前是复杂伤口修复的金标准，但其发病率很高，包括过度疼痛和不适、感染风险、移植皮肤丢失、变色、疤痕、移植物和供体部位相关感觉丧失。这种方法也受到健康皮肤可用性的限制，对于严重烧伤患者来说不是一种可行的治疗选择。因此，开发治疗大面积全层伤口的替代疗法势在必行。Sharklet Technologies, Inc. （STI）提议进行创新研发，专注于改善全层伤口的治疗，这与美国国立卫生研究院（NIH）内几个研究所的使命相一致。为了克服现有敷料的局限性，减少对自体皮肤移植的需求，STI提出开发一种先进的双层伤口护理敷料，该敷料由血管诱导的、可生物降解的基质组成，以促进真皮层的愈合，并结合Sharklet微图案顶端层，通过引导细胞迁移到伤口部位来增强自体表皮的愈合。基于我们的初步数据和证据，微地形可以引导皮肤细胞的迁移，我们假设Sharklet微图案表面可以优化，通过增强上皮化来加速伤口愈合。上皮细胞如角质形成细胞覆盖。为了证明这种方法的可行性，提出了以下I期SBIR目标：目标I -证明Sharklet微模式可以使体外模型的愈合率相对于光滑标准至少提高50% (pd0.05)；证明Sharklet微纹敷料在双蒂缺血大鼠皮瓣模型中可使愈合时间缩短至少25% （pd0.05）。我们使用的大鼠模型使我们能够验证大范围非愈合/慢性伤口的愈合行为。第一阶段的成功将导致更大的第二阶段SBIR项目，重点是验证和扩展第一阶段的结果到更接近模拟人类皮肤愈合的猪模型。第二阶段还将包括优化生产过程，以生产鲨鱼图案的原型伤口敷料。第二阶段将通过展示开发创新产品的潜力，提供与一个或多个第三阶段商业化合作伙伴合作所需的数据，该产品使用经过验证和专有的Sharklet微地形来加速自体伤口愈合。三期金融和行业合作伙伴将参与并支持后续临床试验和商业化。STI已经通过之前的三期合作展示了将深圳经济合作局资助的创新商业化的经验。

DESCRIPTION (provided by applicant): Nearly 12 million wounds are treated in U.S. emergency departments every year. Skin wounds such as severe burns, large trauma wounds, or non-healing/chronic wounds that are too extensive or complex to close by natural healing are often reconstructed using autologous skin grafts. Although autologous skin grafts are currently the gold standard in complex wound repair, there are significant rates of morbidities, including excessive pain and discomfort, risk of infection, loss of grafted skin, discoloration, scarring, an loss of sensation associated with both the graft and donor sites. This approach is also limited by the availability of healthy skin and is not a viable treatment option for severe burn patients. It s thus imperative to develop alternative treatments for large, full-thickness wounds. Sharklet Technologies, Inc. (STI) proposes to pursue innovative R&D focused on improving the treatment of full-thickness wounds, consistent with the mission of several institutes within the NIH. To overcome the limitations of current dressings and reduce the need for autologous skin grafts, STI proposes to develop an advanced, bilayer wound care dressing comprised of a vasoinductive, biodegradable matrix to promote healing of the dermis combined with a Sharklet micro-patterned apical layer to enhance autologous epidermal healing via guided cell migration into the wound site. Based on our preliminary data and evidence that microtopographies can guide migration of skin cells, we hypothesize that Sharklet micro-patterned surfaces can be optimized to accelerate wound closure through enhanced epithelialization-i.e., coverage by epithelial cells such as keratinocytes. To demonstrate the feasibility of this approach, the following Phase I SBIR Aims are proposed: AIM I - Demonstrate that Sharklet micro-patterns can increase healing rates in an in vitro model by at least 50% (pd0.05), relative to a smooth standard; and AIM II -Prove that Sharklet micro-patterned dressings reduce healing time by at least 25% (pd0.05) in a bipedicle ischemic rat skin flap model. The rat model we are using allows us to validate healing behavior for a broad range of non-healing/chronic wounds. Phase I success will lead to a larger Phase II SBIR project focused on validating and extending Phase I results into a porcine model that more closely mimics the healing of human skin. Phase II would also include optimization of manufacturing processes to produce the Sharklet-patterned prototype wound dressings. Phase II will be designed to provide the data needed to engage one or more Phase III commercialization partners by demonstrating the potential to develop an innovative product that uses proven and proprietary Sharklet micro- topographies to accelerate autologous wound healing. Phase III financial and industry partners will participate in and support follow-on clinical trials and commercialization. STI has demonstrated experience in commercializing SBIR-funded innovations via previous Phase III collaborations.