Biodegradable Matrices for Bone Healing

用于骨愈合的可生物降解基质

• 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
• 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

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：用于骨愈合的生物可降解基质 每年有超过650万例骨科手术需要使用移植物来修复骨缺损， 我们清静一点.大面积骨缺损的修复是骨重建外科中的一个挑战性问题。多处植骨 包括自体移植物、同种异体移植物和可生物降解的多孔支架在内的选择已常规用于临床 但成功有限。例如，在骨组织工程支架中，组织向内生长限于表面 (BTE)因为在支架中很难获得细胞和营养。孔隙度是支撑 BTE支架中的组织向内生长导致这些用于矫形外科的材料的次优机械性能 应用.因此，有必要开发BTE支架，其将满足孔隙率和生物相容性的要求。 组织向内生长和血管化所必需的，以及承载所必需的最佳机械性能。 此外，骨传导性、骨诱导性和骨整合性特性将提高骨植入的成功率。 移植材料。我们正在进行的研究和出版物已经证明了开发的可行性 由具有不同降解特性的材料制成的机械强度高的无孔复合支架， 导致在复合材料内逐渐形成互连孔 在一段时间内（1，2）。同样地，我们已经证明，使用非线性结构的支架， 旨在促进细胞增殖、浸润和均匀的矿化基质沉积， 脚手架结构（3-6）。这些机械稳定的初始无孔支架能够支撑骨 在大鼠颅骨缺损和兔节段性骨缺损中，通过基质降解形成的多孔结构导致骨长入 不包含生长因子和细胞的骨缺损。基于这些发现，我们假设通过改变 我们将能够创建具有可编程机械的BTE支架， 强度和多孔结构，以更好地满足承重部位的骨愈合要求。研究 该项目将有以下四个阶段：目标1：优化材料成分和几何形状，以实现 必要的机械稳定性和渐进降解的承重骨愈合应用。目标二： 了解支架降解对人骨髓间充质干细胞（MSCs）生长的影响 粘附、浸润、增殖、分化和矿化基质产生。目的3：体内评估 生物相容性和支架内的动态孔形成。目的4：评价骨愈合能力， 具有不同几何形状和机械强度的支架在兔尺骨关键尺寸节段性缺损中的应用。

项目成果

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
• 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.

• DOI: 10.1016/j.bioactmat.2023.09.017
• 发表时间: 2024-02
• 期刊: Bioactive materials
• 影响因子: 18.9

Amorphous silica fiber matrix biomaterials: An analysis of material synthesis and characterization for tissue engineering.

• DOI: 10.1016/j.bioactmat.2022.04.002
• 发表时间: 2023-01
• 期刊: BIOACTIVE MATERIALS
• 影响因子: 18.9
• 作者: Kim, Hyun S.;Kumbar, Sangamesh G.;Nukavarapu, Syam P.
• 通讯作者: Nukavarapu, Syam P.

Fabrication of polylactic acid (PLA)-based porous scaffold through the combination of traditional bio-fabrication and 3D printing technology for bone regeneration.

• DOI: 10.1016/j.colsurfb.2020.111420
• 发表时间: 2021-01
• 期刊: Colloids and surfaces. B, Biointerfaces
• 作者: Zhou X;Zhou G;Junka R;Chang N;Anwar A;Wang H;Yu X
• 通讯作者: Yu X

Polymeric ionically conductive composite matrices and electrical stimulation strategies for nerve regeneration: In vitro characterization.

聚合物电离导电复合矩阵和神经再生的电刺激策略：体外表征。

• DOI: 10.1002/jbm.b.34272
• 发表时间: 2019-08
• 期刊: Journal of biomedical materials research. Part B, Applied biomaterials
• 作者: Manoukian OS;Stratton S;Arul MR;Moskow J;Sardashti N;Yu X;Rudraiah S;Kumbar SG
• 通讯作者: Kumbar SG