Scaffolds with high oxygen content for mineralization

用于矿化的高氧含量支架

基本信息

批准号：
10672956
负责人：
Gulden Camci-Unal
金额：
$ 39.61万
依托单位：
UNIVERSITY OF MASSACHUSETTS LOWELL
依托单位国家：
美国
项目类别：
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/10672956
关键词：
3-Dimensional Address Affect Aging Animal Model Autologous Transplantation Biocompatible Materials Biodegradation Biological Bone Formation Stimulation 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 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 Modeling Morbidity - disease rate Natural regeneration Osteoblasts Osteogenesis Oxygen Patients Performance Peroxides Physiological Polymers Porosity Predisposition Property Proteins Protocols documentation Rattus Recovery of Function Research Site Solid Source Testing Time Tissue Engineering Tissue Grafts Tissues Training Translating Trauma Vascularization Work 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 particle patient population physical property repaired replacement tissue response restoration scaffold subcutaneous tissue regeneration tissue repair tumor wound

项目摘要

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.

抽象的每年，由于创伤，与战斗相关病变，清除肿瘤，先天性异常和衰老。尽管其中一些条件可能是通过使用从另一个部位接枝的患者自身的组织来解决，这种方法使患者容易感染并造成其他创伤。当前可用的治疗和恢复方法颅面缺陷的局限性，自体移植，免疫排斥，高成本，不足植入物特征（氧含量，机械性能，孔隙率，生物相容性，降解，感染风险），缺乏血管化。骨修复对于恢复伤害后患者功能至关重要。脚手架具有易于手柄，廉价，可生物降解，生物活性和非免疫原性，具有足够的孔隙率和足够的孔隙。氧气含量以及适当的机械强度是为修复颅面缺陷而高度搜寻的。植入物材料的选择对于支持受伤患者的恢复至关重要。最近我们开发了由天然衍生的聚合物和产生氧的高度多孔脚手架成分。当与与宿主兼容的细胞源结合使用时，这些支架可以增强颅面组织愈合。我们建议使用易于访问，多孔，可调，可降解的材料，和生物相容性。我们的目的是制造由产生氧气的沉积物和明胶，表征其物理，化学和生物学特性，并研究细胞的分化和这些复合材料中的血管化。我们的初步发现表明提出的新型复合材料水凝胶具有显着改善的机械性能，并表明通过大鼠模型中的皮下植入以及关键大小颅骨缺陷的完全再生。在AIM 1中，我们将合成并表征具有优化性能的生物材料的生物材料和特征它们。在AIM 2中，我们将评估产生氧的沉积物如何影响细胞分化和成骨，并开发出血管化的成骨模型，并评估这些模型构造。在AIM 3中，我们将将这些复合生物材料植入体内的关键尺寸钙钙缺陷中诱导骨再生。我们期望将氧气沉积物的整合到可光叠链接中水凝胶将导致具有改善机械性能的材料，并促进细胞生长，分化，生物矿化和血管化。这些复合生物材料适合修复或颅颌面组织的再生。因为产生氧气的脚手架将具有出色的可可的性能，预计它们在其他时间（例如软骨）的应用也很有用。多孔脚手架具有高氧含量是产生功能性血管化组织的高度有希望的材料，并且是预计将改善颅颌面组织修复和人类健康。