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 此外，41%的美国成年人需要一种或多种治疗，至少23%的65岁以上的成年人需要治疗。 缺牙（缺牙）。随着有牙齿危险的人的比例前所未有的激增， 牙齿缺失、拔牙和种植正在成为越来越普遍的治疗方法。但要实现 为了获得长期和一致的恢复，患者必须有足够的骨量来锚在 提取地点拔牙后通常会发生骨吸收，导致牙槽嵴骨丢失。作为 因此，许多患者缺乏足够的水平或垂直骨，需要使用GBR技术 其再生足够量的骨以确保骨固定。牙齿脱落的患病率和牙齿 尽管技术不断进步，但成年人的腐烂仍然是一个有待解决的问题。Matregenix开发了 MatriNova是一种由小孔径层（SPL）和大孔径层组成的双层BM (LPL)完全集成到一个BM中。MatriNova具有独特的微观结构设计（表面 层），旨在防止软组织侵入，同时促进营养渗透和骨愈合。 Matregenix将利用专有的静电纺丝工艺生产纤维状和高度多孔的 具有可调特性的膜。基于氨基酸的聚酯衍生物，包括PEU， 因为它们的降解副产物是限制毒性的必需氨基酸。PEU已经 显示在体内具有有限的炎症反应。为了联合收割机可调的机械性能和 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 GBR膜通过简单的静电纺丝工艺，具有前所未有的性能，可满足临床医生的 治疗口腔和颅颌面骨缺损的要求。MatriNova将解决 通过消除对动物基材料的需求， 引入一种新的生物材料，有利于伤口愈合、粘连屏障和其他组织 重建应用。与胶原蛋白膜不同，MatriNova不含动物衍生物，避免了风险 动物病原体的媒介传播。MatriNova将是唯一的合成可吸收膜， 不产生酸性副产物，避免组织炎症风险。我们的第一阶段目标是验证 电纺氨基酸基PEU降解膜治疗GBR的临床意义 在牙科中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 使用犬评估双层膜对牙槽骨缺损中骨再生的有效性 模型，并侧重于510（k）申请的临床性能评价。

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.