Scaffolds with high oxygen content for mineralization

用于矿化的高氧含量支架

• 批准号: 10474314
• 负责人: Gulden Camci-Unal
• 金额: $ 39.21万
• 依托单位: UNIVERSITY OF MASSACHUSETTS LOWELL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10474314
• 关键词: 3-Dimensional; Address; Affect; Aging; Animal Model; Autologous Transplantation; Biocompatible Materials; Biodegradation; Biological; Blood Vessels; Bone Regeneration; Bone Tissue; Bone Transplantation; Calcium; Calvaria; Cartilage; Cell Differentiation process; Cell Survival; Cells; Cephalic; Characteristics; Chemicals; Coculture Techniques; Congenital Abnormality; Craniofacial Abnormalities; Data; Defect; Dental; Development; Differentiation and Growth; Encapsulated; Endothelial Cells; Engineering; Excision; Exhibits; Gelatin; Gene Expression Profiling; Generations; Goals; Health; Human; Hybrids; Hydrogels; Hydrophobicity; Immune; Immunohistochemistry; Implant; In Vitro; Infection; Injury; Kinetics; Knowledge; Lesion; Mechanics; Metabolism; Methods; Minerals; Modeling; Morbidity - disease rate; Natural regeneration; Osteogenesis; Oxygen; Patients; Performance; Peroxides; Physiological; Polymers; Porosity; Property; Proteins; Protocols documentation; Rattus; Recovery of Function; Research; Site; Solid; Source; Testing; Thick; Time; Tissue Engineering; Tissue Grafts; Tissues; Training; Translating; Trauma; Vascularization; Work; base; biodegradable scaffold; biomaterial compatibility; biomineralization; bioscaffold; bone; bone cell; bone healing; bone repair; bone scaffold; cell behavior; cell growth; chemical property; clinically relevant; combat; cost; craniofacial; craniofacial repair; craniofacial tissue; craniomaxillofacial; experience; experimental study; graduate student; graft healing; healing; hydrogel scaffold; immunogenic; immunoreaction; implant material; implantation; improved; improved outcome; in vivo; infection risk; injury recovery; innovation; mechanical properties; microCT; mineralization; novel; novel strategies; osteogenic; patient population; physical property; repaired; replacement tissue; response; restoration; scaffold; subcutaneous; tissue regeneration; tissue repair; tumor; wound

ABSTRACT Each year more than 3 million craniofacial injuries occur in the US as a result of trauma, combat-associated lesions, tumor removal, congenital abnormalities, and aging. Although some of these conditions can be addressed by using the patient’s own tissues grafted from another site, this approach leaves the patients susceptible to infections and creates additional trauma. Currently available methods for treatment and restoration of craniofacial defects have limitations with the availability of autografts, immune rejection, high cost, inadequate implant characteristics (oxygen content, mechanical properties, porosity, biocompatibility, degradation, infection risks), and lack of vascularization. Bone repair is crucial to restore patient functionality post-injury. Scaffolds that are easy-to-handle, inexpensive, biodegradable, bioactive, and non-immunogenic with adequate porosity and oxygen content as well as proper mechanical strength are highly sought after for repairing craniofacial defects. The choice of the implant material is of critical importance to facilitate recovery of the injured patients. Recently we developed highly porous scaffolds composed of naturally derived polymers and oxygen-generating components. When combined with cell sources that are compatible with the host, these scaffolds can enhance craniofacial tissue healing. We propose to use materials that are easily accessible, porous, tunable, degradable, and biocompatible. We aim to fabricate hybrid hydrogels that are composed of oxygen-generating depots and gelatin, characterize their physical, chemical, and biological properties as well as studying differentiation of cells and vascularization in these composites. Our preliminary findings suggest that the proposed novel composite hydrogels exhibit significantly improved mechanical properties and indicate a favorable in vivo response by subcutaneous implantation in a rat model as well as full regeneration of critical sized cranial defects. In Aim 1, we will synthesize and characterize oxygen-generating biomaterials with optimized performance and characterize them. In Aim 2, we will assess how the oxygen-generating depots affect cell differentiation and osteogenesis, and develop a vascularized osteogenic model as well as evaluating the functionality of these constructs. In Aim 3, we will implant these composite biomaterials into critical size calvarial defects in vivo to induce bone regeneration. We expect that the integration of oxygen-generating depots into photocrosslinkable hydrogels will result in a material with improved mechanical properties and will promote cell growth, differentiation, biomineralization, and vascularization. These composite biomaterials will be suitable for repair or regeneration of craniomaxillofacial tissues. Because oxygen-generating scaffolds will have outstanding tunability, they are expected to be also useful for applications in other tissues such as cartilage. Porous scaffolds with high oxygen content are highly promising materials for creating functional vascularized tissues, and are expected to improve craniomaxillofacial tissue repair and human health.

摘要