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

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

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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2亿美国人将遭受部分牙齿脱落。此外，41％的美国成年人需要一种或多种治疗，至少需要23％的65岁以上的成年人正在吃（缺乏牙齿）。在有风险的个人比例的比例中，有前所未有的激增损失，牙齿提取和植入正变得越来越普遍。但是，要实现长期且一致的恢复，患者必须具有足够的骨骼体积才能将植入物锚定在提取地点。通常发生骨骼的萃取后分辨率会导致肺泡脊骨质流失。作为结果，许多患者缺乏足够的水平或垂直骨，对于使用GBR技术所必需的这会再生足够的骨头来固定植入。牙齿脱落和牙齿的患病率成年人的衰减仍然是一个问题，要解决的问题是发展技术。 Matregenix已经开发了 Matrinova是一个双层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）层次）旨在防止软组织入侵，同时促进营养浸润和骨骼愈合。 Matregenix将利用专有的静电纺丝工艺产生纤维和高度的多孔具有可调特性的膜。包括PEU在内的氨基酸基聚酯衍生物是由于其降解副产品的吸引力是限制毒性的必需氨基酸。 Peus曾经是显示体内炎症反应有限。结合可调的机械性能和有限的炎症反应随持续降解概况，我们提出了一系列可吸收性共聚物由L-缬氨酸和L-苯基丙氨酸单体组成。这些前体将用于产生 GBR膜通过简单的静电纺丝工艺具有前所未有的特性符合临床的特性治疗口腔和颅骨骨缺陷的要求。 Matrinova将解决差距通过消除对动物基材料的需求，在可吸收和不可吸收的BMS中固有的固有引入一种新的生物材料，以使伤口愈合，广告障碍和其他组织的区域受益重建应用程序。与胶原蛋白膜不同，Matrinova没有动物衍生物，避免了风险动物病原体的载体传播。 Matrinova将是唯一的合成分辨膜不会产生酸性副产品，避免组织注射风险。我们的I阶段目标是验证拟议的电纺氨基酸基于GBR的临床意义牙科的应用。第一阶段的完成将导致Matrinova的工作原型。在第二阶段，我们将评估双层膜在使用犬的巨大缺陷中对骨再生的有效性模型，并专注于510（k）应用的临床性能评估。