Scaffolds with high oxygen content for mineralization

摘要 每年超过300万颅面损伤发生在美国作为创伤的结果，战斗相关的 病变、肿瘤切除、先天性异常和衰老。虽然其中一些条件可以 通过使用从另一个部位移植的患者自身组织来解决，这种方法使患者 易受感染并造成额外的创伤。目前可用的治疗和恢复方法 的颅面缺损具有自身移植物的可获得性、免疫排斥反应、高成本、不充分 植入物特性（氧含量、机械性能、孔隙率、生物相容性、降解、感染 风险）和缺乏血管化。骨修复对于恢复患者损伤后的功能至关重要。的支架 易于处理、便宜、可生物降解、生物活性和非免疫原性，具有足够的孔隙率， 氧含量以及适当的机械强度对于修复颅面缺损是非常需要的。 植入物材料的选择对于促进受伤患者的恢复至关重要。最近 我们开发了高度多孔的支架， 件.当与与宿主相容的细胞来源结合时，这些支架可以增强 颅面组织愈合我们建议使用容易获得、多孔、可调节、可降解的材料， 和生物相容性。我们的目标是制造混合水凝胶，由产氧仓库和 明胶，表征其物理，化学和生物学特性以及研究细胞的分化 和血管化。我们的初步研究结果表明，所提出的新型复合材料 水凝胶显示出显著改善的机械性能， 在大鼠模型中的皮下植入以及临界尺寸的颅骨缺损的完全再生。在目标1中， 我们将合成和表征具有优化性能的产氧生物材料， 描述他们。在目标2中，我们将评估产氧库如何影响细胞分化， 骨生成，并开发血管化的成骨模型，以及评估这些功能 结构。在目标3中，我们将这些复合生物材料植入体内关键尺寸的颅骨缺损中， 诱导骨再生。我们期望将产氧库整合到光可交联聚合物中， 水凝胶将产生具有改善的机械性能的材料并将促进细胞生长， 分化、生物矿化和血管化。这些复合生物材料将适用于修复或 颅颌面组织再生。因为产氧支架具有出色的 由于可调谐性，预期它们也可用于其它组织如软骨中的应用。多孔支架 具有高氧含量的材料是用于产生功能性血管化组织的非常有前途的材料， 有望改善颅颌面组织修复和人类健康。

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.