Scaffolds with high oxygen content for mineralization

摘要 在美国，每年有300多万人因与战斗有关的创伤而发生颅面部损伤 病变、肿瘤切除、先天畸形和衰老。尽管其中一些情况可能是 通过使用从另一个部位移植的患者自己的组织来解决，这种方法让患者 容易受到感染，并造成额外的创伤。目前可用的治疗和修复方法 在自体移植的可获得性、免疫排斥、高成本、不足等方面存在局限性。 植入物特性(含氧量、机械性能、孔隙率、生物相容性、降解、感染 风险)，以及缺乏血管形成。骨修复是恢复患者损伤后功能的关键。脚手架 易于处理，价格低廉，可生物降解，具有生物活性和非免疫原性，具有足够的孔隙度和 氧含量和适当的机械强度在修复颅面缺损方面备受追捧。 植入物材料的选择对于促进受伤患者的康复至关重要。最近 我们开发了由天然衍生聚合物和产氧剂组成的高度多孔的支架 组件。当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。我们建议使用易于获得、多孔、可调、可降解的材料， 和生物相容。我们的目标是制造混合水凝胶，它由产氧库和 明胶，表征它们的物理、化学和生物学特性以及研究细胞的分化 以及这些复合材料中的血管形成。我们的初步研究结果表明，拟议的新型复合材料 水凝胶表现出显著的机械性能改善，并显示出良好的体内响应 在大鼠模型中进行皮下植入，并完全再生临界大小的颅骨缺损。在目标1中， 我们将合成和表征性能优化的产氧生物材料和 描述它们的特征。在目标2中，我们将评估产氧库如何影响细胞分化和 成骨，并开发血管成骨模型，以及评估这些功能 构造。在目标3中，我们将这些复合生物材料植入体内临界大小的颅骨缺损中，以 诱导骨骼再生。我们期望产氧库与光交联剂的结合 水凝胶将产生具有更好的机械性能的材料，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 颅颌面部组织的再生。因为制氧支架将会有出色的 由于可调性，它们有望在软骨等其他组织中得到应用。多孔支架 高含氧量是创建功能性血管组织的极有希望的材料，并且是 有望促进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.