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

• 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
• 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

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型混合无机-有机支架生产工程化骨软骨界面，该支架的化学和物理性质梯度使其能够通过相关的人骨髓间充质干细胞（MSC）诱导骨样基质逐渐过渡到纤维软骨样基质生产。在骨科重建中，例如前交叉韧带（ACL），软组织移植物往往由于整合不良而不成功 相关的骨是由于不能再现天然的“软”骨软骨界面-从纤维软骨样基质逐渐过渡到骨样基质。再生策略，以重新建立骨软骨界面可能受益于最近的报告表明，在支配相关的细胞行为的内在支架性能的有效性质。在设计促进骨软骨再生的支架时，存在两个主要挑战：（1）关于通过MSC“最佳地”诱导骨或纤维软骨再生的支架性质的有限知识，和（2）具有性质逐渐转变的支架的开发，所述性质逐渐转变内在地促进MSC行为的期望的逐渐转变。鉴于先前的文献证明了无机疏水性材料的骨诱导性质，我们假设无机-有机混合支架可以特异性地工程化，具有梯度化学和物理性质，这将诱导MSC从骨向纤维软骨分化的逐渐过渡。所提出的“梯度支架”是基于无机的、疏水的甲基丙烯酸化的星星聚二甲基硅氧烷（PDMSstar-MA）和有机的、亲水的聚（乙二醇）二丙烯酸酯（PEG-DA）的组合。PI是第一个报道将PDMS共大分子单体引入PEG-DA支架中的人，这些研究表明，PDMS共大分子单体不仅拓宽了可实现的支架特性，而且还调节了细胞行为，包括MSC的行为。不同极性的制造溶剂将用于定制PDMS分布和孔隙率。使用现有的梯度制备技术，将支架制备为梯度，以允许快速筛选诱导的MSC行为。根据这些结果，无机-有机梯度支架将在体外再生骨软骨界面。目前R 03的具体范围是建立我们假设的可行性，即这些梯度支架 化学性质（例如无机物含量、化学官能度和亲水性）和物理性质（例如形态、孔隙率和模量）将足以诱导所需的MSC分化。该小组由拟议工作所有关键领域的专家组成。Melissa Grunlan（PI）将领导制作支架的工作。Mariah Hahn教授（PI）将领导这些支架的组织工程研究。将由骨科重建专家Walter Lowe博士（顾问）提供输入。