A Novel Scaffold to Promote Skin Regeneration

促进皮肤再生的新型支架

• 批准号: 9346873
• 负责人: Howard Levinson
• 金额: $ 22.5万
• 依托单位: XEQUEL BIO, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-14 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9346873
• 关键词: Acute; Affect; Animals; Autologous Transplantation; Blast Cell; Blinded; Burn injury; C57BL/6 Mouse; Cicatrix; Collagen; Contracture; Cosmetics; Deposition; Dermal; Development; Dimensions; Electrospinning; Epithelium; Etiology; Family suidae; Fiber; Fibrosis; Goals; Graft Survival; Granulation Tissue; Guidelines; Human; Hypertrophic Cicatrix; Infection; Inflammation; Injury; Investigation; Mechanics; Medical; Methods; Military Personnel; Modeling; Molds; Mus; One-Step dentin bonding system; Operative Surgical Procedures; Organic solvent product; Particulate; Patients; Physical therapy; Polymers; Porosity; Production; Property; Publishing; Quality of life; Risk; Rodent; Rodent Model; Safety; Skin; Skin Substitutes; Skin graft; Solvents; Structure; Technology; Testing; Thick; Tissue Engineering; Tissues; Translating; Water; Work; Wound Healing; base; bench to bedside; biomaterial compatibility; caprolactone; copolymer; cost; design; follow-up; healing; implantation; improved; in vivo; injured; mechanical properties; novel; particle; prevent; restoration; scaffold; skin regeneration; subcutaneous; synthetic peptide combinatorial library; tissue support frame; uptake; vehicular accident; viscoelasticity; voltage; wound

PROJECT SUMMARY: Dermal scarring affects more than 80 million people worldwide annually - over 4.4 million people are injured in motor vehicle accidents, over 2.4 million patients are severely burned, and thousands of warriors are wounded in military blasts. In severe burns, more than 40% of patients develop hypertrophic scar contraction, which leads to hypertrophic scar contractures (HSc). HSc are stiff, shrunken scars that limit mobility, impact quality of life and cost millions of dollars per year in surgical treatment and physical therapy. HSc are caused by increased mechanical tension and occur 6-12 months after injury. Current tissue engineered scaffolds, such as IntegraTM, have mechanical properties akin to unwounded skin, but the collagen based scaffolds rapidly degrade over 2 months, being too short-lived to prevent HSc. The key to preventing HSc is having a biocompatible scaffold which degrades over 12 months. To achieve this goal, the development of scaffolds composed of viscoelastic copolymer, poly(ι-lactide-co-ε-caprolactone) (PLCL) is proposed. Published work has demonstrated that electrospun ~100 µm thick PLCL scaffolds possess appropriate mechanical properties for implantation beneath skin grafts and inhibition of HSc in mice. However, electrospinning cannot be used to generate scaffolds at thickness necessary for large animal studies due to the great voltage gradient required for scaffold production. To overcome this hurdle solvent casting/particulate leaching (SCPL) will be used to create 3D porous PLCL scaffolds. This method involves the mixing of polymers with particles within an organic solvent followed by casting into a mold. Water is then passed through the mold to leach out the particles, resulting in an interconnected porous 3D scaffold. This SPCL method has successfully been used to create 2mm thick PLCL scaffolds, which have appropriate mechanical properties and tunable porosity for implantation beneath skin grafts. We hypothesize that optimized SCPL PLCL scaffolds will promote graft bioincorporation and dampen fibrosis in vivo. The three Aims to test our hypothesis are: Aim 1. Determine SCPL manufacturing parameters to create uniform PLCL scaffolds with controlled pore size, porosity, and mechanical properties. Aim 2. Determine the optimal porosity of collagen coated SCPL PLCL scaffolds for tissue ingrowth. Aim 3. Evaluate the safety and efficacy of optimal porosity PLCL scaffolds at promoting skin graft survival. The completion of these aims will validate a scalable method to create PLCL scaffolds and test them in rodent and swine wound models for safety and efficacy. The results will bring us closer toward developing an optimized technology that prevents HSc with the potential to improve millions of lives worldwide.

项目概要： 皮肤瘢痕每年影响全球超过8000万人-超过440万人 在机动车事故中受伤，超过240万患者严重烧伤，成千上万的战士 在军事爆炸中受伤在严重烧伤中，超过40%的患者会出现增生性瘢痕收缩， 导致增生性瘢痕挛缩（HSc）。HSc是僵硬的，萎缩的疤痕，限制了活动性，影响 生活质量，每年花费数百万美元用于手术治疗和物理治疗。HSc是由 在受伤后6-12个月内发生。目前的组织工程支架，如 作为IntegraTM，具有类似于未受伤皮肤的机械性能，但基于胶原蛋白的支架迅速 降解超过2个月，寿命太短，无法预防HSc。预防HSc的关键是 生物相容性支架在12个月内降解。为了实现这一目标，支架的发展 提出了一种由粘弹性共聚物组成的聚（1-丙交酯-co-ε-己内酯）（PLCL）。出版的作品有 证明了电纺~100 µm厚的PLCL支架具有适当的机械性能， 在小鼠中的皮肤移植物下植入和HSc抑制。然而，静电纺丝不能用于 由于需要很大的电压梯度，产生大型动物研究所需厚度的支架 用于脚手架生产。为了克服这一障碍，将使用溶剂浇铸/颗粒沥滤（SCPL）来 创建3D多孔PLCL支架。该方法涉及将聚合物与有机聚合物中的颗粒混合。 溶剂，然后浇铸到模具中。然后使水通过模具以滤出颗粒， 产生互连的多孔3D支架。此SPCL方法已成功用于创建 2 mm厚PLCL支架，具有适当的机械性能和可调的植入孔隙率 在皮肤移植物下面。我们假设，优化的SCPL PLCL支架将促进移植物生物掺入 抑制体内纤维化。检验我们假设的三个目标是： 目标1。确定SCPL制造参数，以创建具有受控孔径的均匀PLCL支架， 孔隙率和机械性能。 目标二。确定胶原蛋白涂层SCPL PLCL支架用于组织向内生长的最佳孔隙率。 目标3。评价最佳孔隙率PLCL支架在促进皮肤移植物存活方面的安全性和有效性。 这些目标的完成将验证一种可扩展的方法来创建PLCL支架并在环境中测试它们。 啮齿动物和猪伤口模型的安全性和有效性。这些结果将使我们更接近于开发一种 优化的技术，防止HSc，有可能改善全球数百万人的生活。