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

用于引导骨再生的电纺氨基酸基聚（酯脲）生物可降解屏障膜

基本信息

批准号：
10545224
负责人：
Sherif Soliman
金额：
$ 25.08万
依托单位：
MATREGENIX
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-01 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10545224
关键词：
Address Adhesions Adult Age-Years Agreement Alveolar Alveolar ridge American Amino Acids Animals Area Biocompatible Materials Bone Regeneration Bone Resorption Bone Transplantation Cells Clinical Collagen Complex Cyclic GMP Defect Dental Dental caries Dentistry Dentists Devices Edentulous Mouth Electrospinning Epithelial Essential Amino Acids Esters Evaluation Future Goals Gold Implant Individual Infiltration Inflammation Inflammatory Response Interview Licensing Membrane Natural regeneration Nutrient Oral Oral Surgeon Patients Performance Phase Phenylalanine Polyesters Polymers Prevalence Price Procedures Process Property Recovery Regenerative capacity Risk Secure Series Shapes Side Site Surface Surveys Techniques Technology Tissues Tooth Loss Tooth structure Toxic effect Urea Valine Xenograft procedure base bone bone healing bone loss canine model clinically significant copolymer cost cost effective craniomaxillofacial design effectiveness evaluation experience implantation improved in vitro Assay in vivo in vivo Model innovation insight mechanical properties monomer novel pathogen prevent prototype soft tissue tissue reconstruction vector transmission wound healing

项目摘要

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.

抽象的在美国，预计到 2027 年，超过 2 亿美国人将出现部分牙齿缺失。此外，41% 的美国成年人需要一种或多种治疗，并且至少 23% 的 65 岁以上成年人需要接受一种或多种治疗无牙颌（缺乏牙齿）的人口比例空前激增。然而，拔牙和种植牙是一种越来越普遍的治疗方法。为了实现长期一致的恢复，患者必须有足够的骨量来将种植体固定在拔牙后通常会发生骨吸收，导致牙槽嵴骨丢失。因此，许多患者缺乏足够的水平或垂直骨，需要使用 GBR 技术再生足够量的骨骼以确保植入。牙齿脱落和牙齿的流行。尽管 Matregenix 已经开发出了先进的技术，但成人的腐烂仍然是一个有待解决的问题。 MatriNova 是由小孔径层 (SPL) 和大孔径层组成的双层 BM (LPL) 完全集成到一个 BM 中，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骼愈合。 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性能的膜是基于氨基酸的聚酯衍生物，其中包括PEU。其降解副产物是限制毒性的必需氨基酸，因此很有吸引力。结合了可调节的机械性能和体内炎症反应。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将用于生产 GBR 膜通过简单的静电纺丝工艺制成，具有前所未有的特性，可满足临床医生的需求治疗口腔和颅颌面骨缺陷的要求将弥补这一差距。通过消除对动物材料的需求，可吸收和不可吸收的BM固有的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领域与胶原膜不同，MatriNova 不含动物衍生物，避免了风险。 MatriNova 将是唯一能够抑制动物病原体媒介传播的合成可吸收膜。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。所提出的电纺氨基酸基 PEU 可降解膜用于 GBR 的临床意义第一阶段的完成将产生 MatriNova 的工作原型。使用犬评估双层膜对牙槽缺损骨再生的有效性模型，并重点关注 510(k) 应用的临床性能评估。