Multicomponent Composites for Bioengineering of Dental Bone Tissue

描述(由申请人提供)：由于肿瘤切除、感染、创伤以及牙齿脱落或拔除而导致的颌面部骨质缺陷，通常与患者的发病率有关。通过引导骨再生(GBR)重建口腔结构的合适生物材料的开发降低了发病率，提高了术后生活质量，并通过支持用于修复缺失牙齿的种植体，使部分或全部无牙患者受益。GBR技术主要使用聚合物屏障膜来阻止周围不需要的软组织渗透到缺损处，并支持新骨形成。目前可用的阻隔膜显示出明显的不足。例如，非生物可吸收膜在组织愈合后需要进行第二次手术才能移除。人工合成的生物可吸收膜消除了二次手术的需要，并提供了足够的机械强度，但它们在降解过程中会导致局部炎症。天然的生物可吸收膜(主要是胶原蛋白)可消除炎症，但仍存在快速降解和机械强度不足的问题。更重要的是，这些膜都不提供可调节的生物活性物质(骨诱导蛋白、生长因子、抗生素)的释放，以促进新骨组织的形成。因此，需要一种具有合适的生物相容性、力学性能和生物活性物质释放的生物材料。我们建议制备一种新型的多组分复合膜，其中包括一种具有刺激响应性的智能聚合物(弹性蛋白样多肽，ELP)、可生物降解的陶瓷(45S5生物玻璃)和作为网络前体的胶原蛋白。主要成分ELP经过基因工程设计，可精确控制其性质，并随着溶液环境的变化而表现出相反的相变行为。我们假设ELP和Bioglass的加入将改善膜的力学性能，而ELP的逆相变行为将控制生物活性物质的释放速率。本研究分为以下几个主要目标：(1)制备和表征ELP-生物玻璃-胶原膜；(2)表征复合膜的药物释放特性；(3)评价用于成骨细胞培养的载药ELP-生物玻璃-胶原膜。我们的研究将显著影响目前限制GBR中同时药物输送和组织工程的屏障膜开发的主要技术和生物学问题，并有助于实现：(1)生物活性物质的持续释放；(2)促进骨组织生长；(3)减少手术后细菌感染和周围不需要的软组织的渗透。在促进对细胞外基质基复合材料的基础认识的同时，我们的研究将为GBR和其他需要骨替代的应用提供新的复合材料。因此，新型ELP-生物玻璃-胶原材料可能在不久的将来直接影响生物医学技术。

DESCRIPTION (provided by applicant): Maxillofacial bony defects, occurring as a result of tumor resection, infection, trauma, as well as tooth loss or extraction, are often associated with patient morbidity. Development of suitable biomaterials for reconstruction of oral structures through guided bone regeneration (GBR) has reduced morbidity, improved quality of life after surgery, and has benefitted partially or completely edentulous patients by supporting dental implants used to replace the lost teeth. The GBR techniques primarily use a polymeric barrier membrane to stop infiltration of surrounding undesired soft tissue into the defect site and support new bone formation. Currently available barrier membranes display significant shortfalls. For example, the non- bioresorbable membranes need a second surgery for their removal after tissue healing. The synthetic, bioresorbable membranes eliminate this need for the second surgery and provide sufficient mechanical strength but they lead to local inflammation during degradation. The natural, bioresorbable membranes (primarily collagen) eliminate inflammation, but still suffer from rapid degradation and inadequate mechanical strength. More importantly, none of these membranes offer a tunable release of bioactive agents (osteoinductive proteins, growth factors, antibiotics) to enhance the new bone tissue formation. Therefore, it is desirable to have a biomaterial with suitable biocompatibility, mechanical properties, and bioactive agent release. We propose to prepare novel multi-component composite membranes that incorporate a stimulus- responsive smart polymer (elastin-like polypeptide, ELP), biodegradable ceramic (45S5 Bioglass), and collagen as network former. The major component, ELP, is genetically engineered to provide precise control of its properties and exhibits an inverse phase transition behavior in response to changes in its solution environment. We hypothesize that incorporation of ELP and Bioglass will improve the mechanical properties of the membranes, while the inverse phase transition behavior of ELP will control the release rates of bioactive agents from the membranes. This research is divided into following key Specific Aims: (1) Create and Characterize ELP-Bioglass-Collagen Membranes; (2) Characterize Drug Release Profiles for Composite Membranes; (3) Evaluate Drug-loaded ELP-Bioglass-Collagen Membranes for Osteoblast Culture. Our research will significantly impact major technological and biological problems that currently limit the development of barrier membranes for simultaneous drug delivery and tissue engineering in GBR and help achieve: (1) sustained release of bioactive agents; (2) improved bone tissue growth; and (3) reduced post- surgical bacterial infections and infiltration of surrounding undesired soft tissue. While advancing the fundamental understanding of extra-cellular matrix-based composites, our research will provide new composite materials for GBR and other applications requiring bone replacement. Thus, the new ELP- Bioglass-Collagen materials may directly impact biomedical technology in the near future.