Electrospun Amino Acid-based Poly(ester urea) Biodegradable Barrier Membrane for Guided Bone Regeneration

摘要 在美国，预计到2027年，将有超过2亿美国人经历部分牙齿脱落。在……里面 此外，41%的美国成年人需要一种或多种治疗，65岁以上的成年人中至少有23% 无牙(缺牙)。有牙齿风险的个体比例空前激增 脱牙、拔牙和种植正成为一种日益普遍的治疗方法。然而，要实现 要获得长期和持续的康复，患者必须有足够的骨量来固定种植体 撤离地点。拔牙后常发生骨吸收，导致牙槽突骨丢失。AS 因此，许多患者缺乏足够的水平或垂直骨，需要使用GBR技术。 可以再生足够数量的骨骼来固定植入物。牙齿缺失和牙齿缺失的患病率 尽管技术进步，成年人的衰老仍然是一个有待解决的问题。Matregenix已经开发出 MatriNova是由小孔尺寸层(SPL)和大孔尺寸层(SPL)组成的双层BM (LPL)完全集成到一个BM中。MatriNova拥有独特的微结构设计(表面 层)，旨在防止软组织入侵，同时促进营养渗透和骨愈合。 Matregenix将利用一种专有的电纺工艺来生产纤维状和高度多孔的产品 具有可调性能的膜。基于氨基酸的聚酯衍生物，包括PEUS，是 由于它们的降解副产物是限制毒性的必需氨基酸，因此很有吸引力。皮乌斯一直在 在活体内表现出有限的炎症反应。将可调的机械性能和 有限的炎症反应和持续的降解特征，我们提出了一系列可吸收的 由L-缬氨酸和L-苯丙氨酸单体组成的共聚物。这些前体将用于生产一种 GBR膜通过简单的电纺工艺，具有前所未有的性能，满足临床医生的要求 治疗口腔和颅颌面骨缺乏症的要求。MatriNova将解决这些差距 通过消除对以动物为基础的材料的需要而固有的可再吸收和不可再吸收的BMS 引入一种新的生物材料，使伤口愈合、粘连屏障和其他组织受益 重建应用程序。与胶原膜不同，MatriNova不含动物衍生品，避免了风险 动物病原体的媒介传播。MatriNova将是唯一一种合成可吸收膜 不产生酸性副产物，避免组织发炎风险。我们的第一阶段目标是验证 新型电纺氨基酸聚乙二醇酯可降解膜的临床意义 在牙科领域的应用。第一阶段的完成将导致MatriNova的工作原型。在第二阶段，我们将 利用犬牙槽骨缺损评价双层膜修复牙槽骨缺损的效果 模型，并将重点放在510(K)应用的临床性能评估上。

Abstract In the US, it is projected that by 2027 more than 200 million Americans will experience partial tooth loss. In addition, 41% of American adults need one or more treatments and at least 23% of adults over 65 years of age are edentulous (lacking teeth). With an unprecedented surge in the proportion of individuals at risk for tooth loss, dental extraction, and implantation, is becoming an increasingly prevalent treatment. However, to achieve a long-term and consistent recovery, patients must have adequate bone volume to anchor an implant at the extraction site. Post-extraction resorption of bone commonly occurs which leads to alveolar ridge bone loss. As a result, many patients lack sufficient horizontal or vertical bone, necessitating the use of GBR techniques which regenerate adequate amounts of bone for securing implantations. The prevalence of tooth loss and tooth decay in adults remains a problem to be solved, despite advancing technologies. Matregenix has developed MatriNova which is a bi-layered BM composed of a small pore size layer (SPL) and a large pore size layer (LPL) that are fully integrated into one BM. MatriNova possesses unique microstructural design (surface layers) aimed at preventing soft tissue invasion, while promoting nutrient infiltration and bone healing. Matregenix will utilize a proprietary electrospinning processes to produce fibrous and highly porous membranes with tunable properties. Amino acid-based polyester derivatives, which includes PEUs, are appealing as their degradation by-products are essential amino acids which limits toxicity. PEUs have been shown to have a limited inflammatory response in vivo. To combine the tunable mechanical properties and limited inflammatory response with sustained degradation profile, we propose a series of resorbable copolymers consisting of L-valine and L-phenylalanine monomers. These precursors will be used to produce a GBR membrane via simple electrospinning process with unprecedented properties that meet the clinician’s requirements in treating oral and craniomaxillofacial bone deficiencies. MatriNova will address the gaps inherent in both resorbable and nonresorbable BMs by eliminating the need for animal-based materials while introducing a new biomaterial to benefit the areas of wound healing, adhesion barriers, and other tissue reconstruction applications. Unlike collagen membranes, MatriNova is free from animal derivates, avoiding risk of vector transmission of animal pathogens. MatriNova will be the only synthetic resorbable membrane that does not produce acidic by-products, avoiding tissue inflammation risks. Our Phase I goal is to validate the clinical significance of the proposed electrospun amino acid based PEU degradable membrane for GBR applications in dentistry. Phase I completion will lead to a working prototype of MatriNova. In Phase II we will assess the effectiveness of the bilayered membrane on bone regeneration in an alveolar defect using a canine model, and focus on the clinical performance evaluation for a 510(k) application.