Biodegradable Matrices for Bone Healing

用于骨愈合的可生物降解基质

基本信息

批准号：
9987102
负责人：
Sangamesh Gurappa Kumbar
金额：
$ 8.27万
依托单位：
UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-11-01 至 2021-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9987102
关键词：
3-Dimensional Allografting Architecture Autologous Transplantation Bone Growth Bone Marrow Bone Matrix Bone Regeneration Bone Tissue Bone Transplantation Buffers Calcium Calvaria Cell Adhesion Cell Differentiation process Cell Proliferation Cells Clinic Clinical Defect Deposition Development Event Geometry Glycolates Growth Factor Human Implant In Situ In Vitro Infiltration Ions Light Mechanics Mediating Mesenchymal Stem Cells Minerals Modeling Natural regeneration Nutrient Orthopedic Procedures Orthopedics Oryctolagus cuniculus Osteoblasts Osteogenesis Performance Phase Phenotype Polymers Porosity Production Property Publications Rattus Reconstructive Surgical Procedures Research Research Project Grants Site Solid Structure Surface System Testing Time Tissue Engineering Tissues Transplanted tissue Vascularization Vertebral column Weight-Bearing state base biomaterial compatibility bone bone healing bone repair material calcium phosphate clinical application cortical bone craniofacial design implantation improved in vivo innovation mechanical properties osteoblast differentiation poly(lactic acid)polycaprolactone programs reconstruction repaired sample fixation scaffold skeletal skeletal disorder stem cell differentiation subcutaneous substantia spongiosa success ulna

项目摘要

Project Summary/Abstract: Biodegradable Matrices for Bone Healing More than 6.5 million orthopaedic procedures require the use of grafts to repair bone defects every year in the US alone. Repair of large bone defects is a challenging problem in reconstructive surgery. Several bone graft options including autografts, allografts, and biodegradable porous scaffolds have been routinely used in the clinics with limited success. For example, tissue ingrowth is limited to the surface in bone tissue engineering scaffolds (BTE) because of poor access to cells and nutrients within scaffolds. The porosity that is necessary to support tissue ingrowth in BTE scaffolds results in sub-optimal mechanical properties of these materials for orthopedic applications. Therefore, there is a need to develop BTE scaffolds which will fulfill the requirements of both porosity necessary for tissue ingrowth and vascularization, and optimal mechanical properties necessary for load bearing. In addition, osteoconductive, osteoinductive, and osteointegrative properties will improve the success of bone graft materials. Our ongoing studies and publications have demonstrated the feasibility of developing mechanically strong non-porous composite scaffolds from materials with differential degradation profiles that result in the progressive formation of interconnected pores within the composite material allowing tissue ingrowth over a period of time (1, 2). Likewise, using spirally structured scaffolds we have shown that geometry can be designed to promote cell proliferation, infiltration, and homogenous mineralized matrix deposition throughout the scaffold architecture (3-6). These mechanically stable initially non-porous scaffolds were able to support bone ingrowth due to evolving porous architecture via matrix degradation in rat calvarial defects and rabbit segmental bone defects without inclusion of growth factors and cells. Based on these findings we hypothesize that by altering scaffold composition and geometry we will be able to create BTE scaffolds with programmable mechanical strength and porous structure to better serve the bone healing requirements at load bearing sites. The research project will have the four following phases: Aim 1: To optimize material composition and geometry to achieve necessary mechanical stability and progressive degradation for load-bearing bone-healing applications. Aim 2: To understand the effect of scaffold degradation on human bone marrow derived mesenchymal stem cell (MSCs) adhesion, infiltration, proliferation, differentiation, and mineralized matrix production. Aim 3: To assess in vivo biocompatibility and dynamic pore formation within the scaffolds. Aim 4: To evaluate the bone healing ability of scaffolds with different geometry and mechanical strength in a critical size segmental defect in the rabbit ulna.

项目摘要/摘要：可生物降解的骨骼愈合矩阵超过650万的骨科手术要求每年使用移植物来修复骨缺陷我们一个人。修复大骨缺损是重建手术中的一个具有挑战性的问题。几个骨移植诊所常规使用了包括自体移植，同种异体移植和可生物降解的多孔脚手架的选项成功有限。例如，组织向内生长仅限于骨组织工程支架中的表面（BTE）由于脚手架内的细胞和营养不良，因此（BTE）。支撑所需的孔隙率 BTE支架中的组织向内生长导致这些材料对骨科的亚最佳机械性能申请。因此，有必要开发BTE脚手架，以满足两种孔隙的要求对于组织向内生长和血管形成以及负载轴承所需的最佳机械性能所需的。此外，骨导导，骨诱导和骨质的特性将改善骨骼的成功移植物材料。我们正在进行的研究和出版物已经证明了发展的可行性机械强大的非孔的复合支架，来自具有差分降解曲线的材料导致复合材料内相互连接的孔的进行性形成，使组织向内生长在一段时间内（1，2）。同样，使用螺旋结构的支架，我们表明几何形状可以是旨在促进细胞增殖，浸润和均匀的矿化基质沉积脚手架建筑（3-6）。这些机械稳定的最初非孔支架能够支撑骨骼通过大鼠钙钙缺陷和兔子节段中的基质降解而导致多孔架构导致的生殖骨骼缺陷而不包含生长因子和细胞。根据这些发现，我们通过更改来假设脚手架成分和几何形状我们将能够使用可编程机械制作BTE脚手架强度和多孔结构，以更好地满足负载轴承部位的骨骼愈合要求。研究项目将具有以下四个阶段：目标1：优化材料成分和几何形状以实现用于承载负荷骨骼治疗应用的必要机械稳定性和进行性降解。目标2：了解支架降解对人骨髓衍生的间充质干细胞（MSC）的影响粘附，浸润，增殖，分化和矿化基质产生。目标3：评估体内脚手架内的生物相容性和动态孔形成。目标4：评估骨骼愈合能力在兔尺骨中，具有不同几何形状和机械强度不同的几何形状和机械强度的支架。

项目成果

期刊论文数量（28）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Nanomaterials/Nanocomposites for Osteochondral Tissue.

DOI：
10.1007/978-3-319-76711-6_4
发表时间：
2018
期刊：
Advances in experimental medicine and biology
影响因子：
0
作者：
Ohan S. Manoukian;Connor Dieck;T. Milne;C. Dealy;Swetha Rudraiah;S. Kumbar
通讯作者：
Ohan S. Manoukian;Connor Dieck;T. Milne;C. Dealy;Swetha Rudraiah;S. Kumbar

Decellularized extracellular matrix biomaterials for regenerative therapies: Advances, challenges and clinical prospects.