Biostimulatory nanofiber-hydrogel composite for soft tissue remodeling

用于软组织重塑的生物刺激纳米纤维-水凝胶复合材料

• 批准号: 10391846
• 负责人: AARON W JAMES
• 金额: $ 56.86万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10391846
• 关键词: Adipose tissue; Affect; Allogenic; Animal Model; Autologous; Biocompatible Materials; Blood Vessels; Caliber; Cell Communication; Cell Differentiation process; Cell Lineage; Cell Therapy; Cells; Chemicals; Chemosensitization; Clinical; Collagen; Coupled; Defect; Deposition; Development; Devices; Disease; Dose; Engineering; Excision; Extracellular Matrix; Face; Fatty acid glycerol esters; Fiber; Fibrosis; Filler; Future; Goals; Health Care Costs; Hyaluronic Acid; Hydrogels; Immune response; Immunocompetent; Implant; Infection; Infiltration; Inflammatory; Inflammatory Response; Inguinal region; Injections; Kinetics; Length; Modeling; Molecular Weight; Morbidity - disease rate; Nucleic Acids; Oryctolagus cuniculus; Outcome; PTPRC gene; Paracrine Communication; Patients; Polyesters; Pre-Clinical Model; Property; Prosthesis; Proteins; Rattus; Reconstructive Surgical Procedures; Rodent Model; Role; Series; Site; Speech; Structure; Structure-Activity Relationship; Surgical Flaps; Testing; Time; Tissue Survival; Tissues; Transplantation; Trauma; Vascularization; angiogenesis; base; caprolactone; care burden; cell motility; clinical translation; conditioning; cost; craniofacial; craniofacial repair; crosslink; density; design; feeding; immunoregulation; implantation; improved; in vivo; insight; lipid biosynthesis; mechanical properties; migration; mouse model; nanofiber; operation; preclinical study; progenitor; reconstruction; recruit; regenerative; regenerative cell; repaired; response; restoration; soft tissue; stem cells; subcutaneous; translational model; translational potential; translational study

PROJECT SUMMARY Restoration of craniofacial soft tissues is a major challenge in reconstructive surgery. Soft tissue losses from congenital facial differences, oncologic resection, trauma, and inflammatory diseases affect millions of patients each year. Current solutions to facial soft tissue losses – both autologous and prosthetic-based – suffer from serious limitations. Autologous solutions such as tissue flaps and lipotransfer are hampered by donor site defects and unpredictable survival, often necessitating repeated operations to achieve adequate restoration. By contrast, prosthetic solutions such as hydrogel fillers or polyester implants are plagued by limited volume and duration of restoration, and by fibrosis, device exposure, and infection respectively. There is a critical need for an engineered, off-the-shelf solution that immediately restores missing soft tissue volume while encouraging natural soft tissue development and remodeling over time. Such an approach to creating well integrated, vascularized soft tissue would greatly decrease the burden of care for craniofacial patients. We recently created a biostimulatory nanofiber-hydrogel composite (NHC), comprised of chemically defined polyester nanofiber and hyaluronic acid (HA) hydrogel components, that is capable of inducing host cell infiltration, pro-regenerative conditioning of tissue responses, and progressive remodeling of the injection site into vascularized soft tissue. Our long-term goal is to use NHC in conjunction with the patient’s own cells as a regenerative cell therapy for craniofacial soft tissue defects. The overall objective for this proposed study is to engineer NHC with high biostimulatory activity coupled with allogeneic cells and define the materials properties and cellular responses governing soft tissue remodeling in genetically tractable and established translational models. In Specific Aim 1, we will engineer optimized nanofiber-hydrogel composites (NHC) as biostimulatory matrices to promote immunomodulation, angiogenesis, and tissue remodeling and define their structure-function relationships. In Specific Aim 2, we will examine the potentiation effects of adipogenic progenitor cells on host cell infiltration and conditioning, angiogenesis, and soft tissue remodeling when co-delivered with biostimulatory NHC. In Specific Aim 3, we will demonstrate soft tissue remodeling capacity in a larger volume preclinical model in rabbits using an optimized combination of biostimulatory NHC and adipose progenitor cells. This study will yield a new series of off-the- shelf biostimulatory NHC matrices capable of remodeling into vascularized soft tissue, elucidate the underlining mechanisms by defining the interplay between biomaterials, autologous cells, and host tissue responses, and offer insights into future clinical utility. The proposed biomaterials and autologous cell approach to craniofacial soft tissue restoration promises to significantly improve clinical outcomes – minimizing morbidity, reducing cost, and expanding accessibility to treatment.

项目摘要 颅面软组织的恢复是重建手术的主要挑战。 先天性面部差异，肿瘤切除，创伤和炎症疾病会影响数百万患者 每年。 诸如组织襟翼lipotransfer之类的血清学被供体部位缺陷阻碍 相比之下，不可预测的生存通常需要重复运行才能实现足够的恢复。 诸如水凝胶填充剂或聚酯植入物之类的假肢溶液被有限的体积和持续时间陷入困境 恢复，并通过纤维化，设备暴露和感染对象。 铺架溶液中恰好导致缺少软组织的架子溶液，同时鼓励天然软组织 随着时间的推移开发和改建。 将大大减轻对颅面专利的护理负担。 纳米纤维 - 凝胶复合材料（NHC），化学定义的聚酯纳米纤维和透明质酸的组成 （HA）能够诱导宿主细胞浸润的水凝胶成分，组织的促再生条件 反应和注射部位的渐进式重塑血管软组织。 将NHC与患者自己的细胞一起用作Cranioft软组织的细胞疗法 缺陷。 与同种异体细胞结合并定义材料特性和细胞响应软组织 在特定目标中进行遗传处理和既定的翻译模型。 优化的纳米纤维 - 凝胶凝胶组合（NHC）作为生物刺激矩阵，以促进免疫调节， 血管生成和组织重塑并定义其结构功能关系。 检查掺杂祖细胞对宿主细胞浸润和调节的潜力， 血管生成和与生物刺激NHC共同进行的软组织重塑。 使用优化的 生物刺激性NHC和脂肪祖细胞的组合将产生新的系列。 货架生物刺激性NHC矩阵，能够重塑为血管化软组织，阐明了下划线 通过定义生物材料，自动学细胞和宿主tisue响应之间的相互作用来进行机制，并 提供对未来临床实用性的见解。 软组织恢复有望显着改善临床结果 - 最大程度地减少发病率，降低成本， 并扩大治疗的可及性。