Hybrid Inorganic-Organic Hydrogel Scaffolds for Osteochondral Regeneration

用于骨软骨再生的混合无机-有机水凝胶支架

基本信息

批准号：
8285559
负责人：
Melissa Grunlan
金额：
$ 7.1万
依托单位：
TEXAS ENGINEERING EXPERIMENT STATION
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-04-01 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8285559
关键词：
Affect Anterior Cruciate Ligament Area Autologous Behavior Bone Marrow Bone Regeneration Cell Culture Techniques Cell Lineage Chemicals Data Degenerative polyarthritis Development Devices Engineering Failure Fibrocartilages Generations Goals Growth Factor Human Hybrids Hydrogels In Vitro Knowledge Lead Ligaments Literature Melissa Mesenchymal Stem Cells Methods Morphology Natural regeneration Nature Operative Surgical Procedures Orthopedics Pathology Patients Porosity Production Property Reporting Research Screening procedure Series Solvents Specialist Stress Surgical sutures Technology Tendon structure Tissue Engineering Tissue Grafts Tissues Ursidae Family Work anterior cruciate ligament reconstruction base bone cell behavior chemical property combinatorial cost design hydrophilicity improved multipotent cell osteochondral tissue physical property poly(ethylene glycol)diacrylate polydimethylsiloxane prevent reconstruction regenerative sample fixation scaffold soft tissue stem cell differentiation success

项目摘要

DESCRIPTION (provided by applicant): Our long-term research goal is to produce an engineered osteochondral interface using new hybrid inorganic-organic scaffolds whose gradient in chemical and physical properties make them uniquely capable of inducing a gradual transition from bone- to fibrocartilage-like matrix production by associated human bone marrow-derived mesenchymal stem cells (MSCs). In orthopedic reconstruction, such as that of the anterior cruciate ligament (ACL), soft tissue grafts are often unsuccessful due to poor integration with the associated bone resulting from a failure to reproduce the native-like "soft" osteochondral interface - a gradual transition from fibrocartilage-like matrix to a bone-like matri. A regenerative strategy to re-establish the osteochondral interface could benefit from recent reports indicating the potent nature of intrinsic scaffold properties in dictating associated cell behavior. In designing scaffolds which promote osteochondral regeneration, two primary challenges exist: (1) the limited knowledge regarding scaffold properties which "optimally" induce regeneration of bone or fibrocartilage by MSCs and (2) the development of scaffolds with a gradual transition in properties which intrinsically promotes the desired gradual transition in MSC behavior. Given previous literature demonstrating the osteoinductive nature of inorganic, hydrophobic materials, we hypothesized that inorganic-organic hybrid scaffolds could be specifically engineered with gradient chemical and physical properties which would induce a gradual transition in MSC differentiation from bone to fibrocartilage. The proposed "gradient scaffolds" are based on a combination of inorganic, hydrophobic methacrylated star polydimethylsiloxane (PDMSstar-MA) and organic, hydrophilic poly(ethylene glycol) diacrylate (PEG-DA). The PIs were the first to report the introduction of a PDMS co-macromer into PEG-DA scaffolds and these studies demonstrated that the PDMS co-macromer not only broadens achievable scaffold properties but also modulates cell behavior, including that of MSCs. Fabrication solvents of varying polarities will be used tailor PDMS distribution and porosity. Using existing gradient- making technologies, scaffolds will be prepared as gradients to permit rapid screening of induced MSC behavior. From these results, a inorganic-organic gradient scaffold will be fabricated to regenerate the osteochondral interface in vitro. The specific scope of the present R03 is establishing the feasibility of our hypothesis that these gradient scaffolds' chemical (e.g. inorganic content, chemical functionality, and hydrophilicity) and physical properties (e.g. morphology, porosity, and modulus) will sufficiently induce desired MSC differentiation. The team is comprised of experts in all key areas of the proposed work. Prof. Melissa Grunlan (PI) will lead efforts to fabricate scaffolds. Prof. Mariah Hahn (PI), will lead tissue engineering studies with these scaffolds. Input will be provided by an orthopedic reconstruction specialist, Dr. Walter Lowe (consultant).

描述（由申请人提供）：我们的长期研究目标是使用新的杂化无机有机脚手架生成工程化的骨软骨界面，其在化学和物理性能中的梯度使它们具有独特的能力，能够诱导与纤维球纤维类似于纤维球纤维的型成纤维的逐渐过渡，并通过相关的人类骨骼骨骼骨骼质质序列（Messemence）的细胞（Mescemallived Marrow-derement-MeSemender-MeSement-Mescemal-MeSemend MeSement-Mescs）（mcs）。在骨科重建中，例如前交叉韧带（ACL）的重建，软组织移植物通常由于整合不良而失败与未能重现天然样的“软”骨软骨界面所产生的相关骨 - 从纤维球橄榄球样基质到骨状Matri的逐渐过渡。重新建立骨软骨界面的再生策略可能会受益于最近的报告，表明在决定相关细胞行为时内在脚手架特性的有效性质。在设计促进骨软骨再生的脚手架时，存在两个主要的挑战：（1）关于脚手架特性的有限知识，这些知识“最佳地”诱导MSCS对骨骼或纤维球杆菌的再生以及（2）脚手架发展的脚手架发展具有内在逐渐促进MSC逐渐过渡的特性的逐渐转移。鉴于以前的文献证明了无机，疏水材料的骨诱导性质，我们假设无机有机杂交脚手架可以通过梯度化学和物理特性进行专门设计，从而诱导MSC从骨骼到纤维球骨灰科的逐渐过渡。所提出的“梯度支架”基于无机，疏水甲基丙烯酸的星聚二甲基硅氧烷（PDMSSTAR-MA）和有机，亲水性聚乙二醇（乙二醇）透明二丙烯酸酯（PEG-DA）的组合。 PI是第一个报告将PDMS共同分子引入PEG-DA支架的人，这些研究表明，PDMS共同分子不仅扩大了可实现的支架特性，而且还可以调节细胞行为，包括MSC。不同极性的制造溶剂将用于裁缝PDMS分布和孔隙率。使用现有的梯度制作技术，将准备脚手架作为梯度，以允许快速筛选诱导的MSC行为。从这些结果中，将制造无机有机梯度支架以在体外重新生成骨软骨界面。当前R03的具体范围是确定我们假设这些梯度支架的可行性化学（例如无机含量，化学功能和亲水性）和物理特性（例如形态，孔隙率和模量）将充分诱导所需的MSC分化。该团队由拟议工作的所有关键领域的专家组成。梅利莎·格伦兰（Melissa Grunlan）教授（PI）将领导制造脚手架的努力。 Mariah Hahn教授（PI）将通过这些脚手架领导组织工程研究。投入将由骨科重建专家Walter Lowe博士（顾问）提供。