Advanced Micro-patterned Wound Dressings for Enhanced Epithelialization

用于增强上皮化的先进微图案伤口敷料

• 批准号: 8832483
• 负责人: Chelsea M Magin
• 金额: $ 21.81万
• 依托单位: SHARKLET TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-18 至 2016-03-17
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8832483
• 关键词: Accident and Emergency department; Address; Adult; Affect; Age; Apical; Area; Autologous; Autologous Transplantation; Behavior; Biopsy; Blood Vessels; Burn injury; Businesses; Caring; Categories; Cells; Chronic; Chronic Disease; Cicatrix; Clinical Trials; Collaborations; Collagen; Comorbidity; Complex; Contracture; Data; Deposition; Dermal; Dermis; Epidermis; Epithelial; Epithelial Cells; Esthesia; Exhibits; Extracellular Matrix; Extracellular Matrix Proteins; Family suidae; Fibroblasts; Forearm; Foundations; Funding; Gold; Graft Rejection; Granulation Tissue; Healed; Histocompatibility Testing; Histologic; Human; Hydrogels; Incidence; Infection; Institutes; Laceration; Lead; Mission; Modeling; Monitor; Morbidity - disease rate; Myofibroblast; Necrosis; Numbness; Outcome; Pain; Patients; Pattern; Phase; Phenotype; Physiological; Plague; Population; Postoperative Period; Process; Pronation; Rattus; Relative (related person); Risk; Site; Skin; Skin graft; Small Business Innovation Research Grant; Speed; Sterile coverings; Surface; Surgical Flaps; Technology; Test Result; Testing; Thick; Time; Trauma; United States National Institutes of Health; Work; Wound Healing; Wrist; alternative treatment; base; cell motility; commercialization; cost; design; dexterity; experience; extracellular; graft failure; graft healing; head/neck injury; healing; improved; in vitro Model; industry partner; innovation; keratinocyte; manufacturing process; migration; neovascularization; pre-clinical; prototype; public health relevance; reconstruction; repaired; research and development; skin discoloration; standard care; success; wound

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.

描述（由申请人提供）：美国急诊科每年治疗近 1200 万个伤口。皮肤伤口，如严重烧伤、大面积创伤伤口或过于广泛或复杂而无法通过自然愈合闭合的不愈合/慢性伤口，通常使用自体皮肤移植来重建。虽然自体皮肤移植目前是复杂伤口修复的黄金标准，但发病率很高，包括过度疼痛和不适、感染风险、移植皮肤脱落、变色、疤痕、与移植和移植相关的感觉丧失。捐助站点。这种方法还受到健康皮肤可用性的限制，对于严重烧伤患者来说不是可行的治疗选择。因此，开发针对大面积全层伤口的替代治疗方法势在必行。 Sharklet Technologies, Inc. (STI) 提议进行创新研发，重点关注改善全层伤口的治疗，这与 NIH 内多个研究所的使命一致。为了克服当前敷料的局限性并减少对自体皮肤移植的需求，STI 建议开发一种先进的双层伤口护理敷料，该敷料由血管诱导性可生物降解基质组成，可促进真皮愈合，并结合 Sharklet 微图案顶层，以实现通过引导细胞迁移到伤口部位来增强自体表皮愈合。根据我们的初步数据和微地形可以引导皮肤细胞迁移的证据，我们假设 Sharklet 微图案表面可以经过优化，通过增强上皮化（即角质形成细胞等上皮细胞的覆盖）来加速伤口闭合。为了证明这种方法的可行性，提出了以下 I 期 SBIR 目标： AIM I - 证明 Sharklet 微图案相对于平滑模型，可以将体外模型中的愈合率提高至少 50% (pd0.05)标准; AIM II - 在双蒂缺血性大鼠皮瓣模型中证明 Sharklet 微图案敷料可将愈合时间缩短至少 25% (pd0.05)。我们使用的大鼠模型使我们能够验证各种不愈合/慢性伤口的愈合行为。第一阶段的成功将导致一个更大的第二阶段 SBIR 项目，重点是验证第一阶段的结果并将其扩展到更接近地模仿人类皮肤愈合的猪模型。第二阶段还将包括优化生产工艺，以生产 Sharklet 图案原型伤口敷料。第二阶段将旨在通过展示开发一种创新产品的潜力，提供吸引一个或多个第三阶段商业化合作伙伴所需的数据，该创新产品使用经过验证的专有 Sharklet 微拓扑来加速自体伤口愈合。第三阶段的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 通过之前的第三阶段合作展示了将 SBIR 资助的创新商业化的经验。