A Biodégradable and Biomimetic Xerogel for Periodontal Bone Regeneration

说明(申请人提供)：牙周骨再生需要注意：(A)需要物理屏障来限制纤维上皮组织的进入/形成，(B)骨丢失的原因是宿主对病理原因的炎症反应，而不是直接由致病病原体引起的；因此，除了骨再生策略外，该过程还同样需要控制炎症，以及(C)避免使用最终需要移除并对新再生组织造成损害的生物材料。这项研究建议设计一种能够解决上述问题的装置。我们已经取得了初步成功，创造了一种可生物降解和可吸收的配方，可以为增殖和生长的骨细胞提供足够的结构和仿生支持。然而，这种装置会生物降解，在所需的21天支持时间之前无法支持再生细胞。这项建议旨在将这种仿生制剂的生物降解时间提高到21-28天，方法是将其成分与无毒和组织保护交联剂进行交联，并将生成的材料设计成干凝胶薄膜/片，以便将其用作物理屏障膜或片，放置在牙周袋中，以在牙周骨再生治疗期间限制纤维上皮组织的进入/形成。所提出的制剂的生物降解性是众所周知的抗炎剂，被认为可以否定炎症宿主对牙周病理的反应。因此，本项目将评估建议的装置的生物降解性和抗炎性，与模拟口腔条件无关，以及长达28天的仿生成骨潜力。在完成这一阶段的研究后，预计它将演变为 更好、更完整的牙周骨再生装置，在实现牙周再生后，无需额外的外科手术来移除物理屏障，即可进行生物降解。在第二阶段的上市前通知(510K)之前，在FDA的监督下对拟议的设备进行进一步开发，并进行后续的临床评估，结果将是一种适销对路的牙周骨再生产品，将把患者的发病率和相关医疗费用降至最低。

DESCRIPTION (provided by applicant): Periodontal bone regeneration requires attention to (a) the need of a physical barrier to restrict the entry/formation of fibro-epithelial tissue, (b) he cause of bone loss that is due to host's inflammatory response to pathological cause and not due to the causative pathogen directly; so, along with bone regeneration strategies, the process also equally demands for inflammation control, and (c) avoid using a biomaterials that would require eventual removal and cause damage to newly regenerated tissue. This research proposes to design a device that will take care of the above issues. We have secured preliminary success in creating a biodegradable and bioabsorbable formulation that may provide sufficient structural and biomimetic support for proliferating and growing bone cells. However, this device would biodegrade and would not be able to support the regenerating cells before the needed time of support of 21 days. This proposal is an effort to enhance the biodegradation time of this biomimetic formulation up to 21-28 days by crosslinking its components with a non-toxic and tissue protective crosslinker and to design the resultant material into a xerogel film/sheet so that it can be used as a physical barrier film or sheet to be placed in periodontal pockets to restrict the entry/formation of fibro-epithelial tissue during the periodontal bone regeneration therapy. The biodegradation of the proposed formulation are well known anti-inflammatory agent that are supposed to negate the inflammatory host response to periodontal pathology. Therefore, this project will evaluate the proposed device for its biodegradation and anti-inflammatory profile inrelated simulated oral conditions and for its biomimetic osteogenic potential for up to 28 days. After completion of this phase-I research, it is expected to evolve a better and more complete periodontal bone regeneration device that would biodegrade without a need for an additional surgical procedure to remove the physical barrier after the periodontal regeneration is achieved. After further development of the proposed device under FDA supervision before the premarket notification (510K) in the phase-II and the following clinical evaluations, the outcome will be a marketable periodontal bone regeneration product that would bring patient morbidity and related medical expenses to a minimum.