Cartilage Regeneration using Colloidal Microgel

使用胶体微凝胶进行软骨再生

• 批准号: 9092766
• 负责人: Debanjan Sarkar
• 金额: $ 7.47万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-15 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9092766
• 关键词: Affect; Age; Animal Model; Arthritis; Biocompatible Materials; Biomimetics; Cartilage; Cartilage Diseases; Cartilage Matrix; Cell Communication; Cells; Characteristics; Chondrocytes; Chondrogenesis; Collagen; Collagen Fiber; Defect; Degenerative polyarthritis; Diffusion; Engineering; Environment; Exhibits; Extracellular Matrix; Force of Gravity; Gel; Goals; Healed; Hydrogels; Injectable; Intercellular Fluid; Liquid substance; Mesenchymal Stem Cells; Modeling; Molecular Structure; Morphology; Movement; Natural regeneration; Outcome Study; Polyethylene Glycols; Polymers; Polyurethanes; Proteoglycan; Prunella vulgaris; Relaxation; Solvents; Stem cells; Structure; Structure-Activity Relationship; Time; Tissue Engineering; Tissues; Transplantation; Water; aqueous; articular cartilage; base; cartilage regeneration; design; functional restoration; healing; in vivo; migration; minimally invasive; particle; public health relevance; repaired; response; restoration; stem cell differentiation; stem cell therapy; viscoelasticity

 DESCRIPTION: Treatment of degenerative joint diseases for structural and functional restoration of cartilage remains a significant challenge. Tissue engineered cartilage with biomaterial based synthetic matrices offer a promising approach, but current biomaterials have shown limited ability for regeneration as these materials cannot mimic the mechanomorphological character of native cartilage matrix which exhibits viscoelastic and poroelastic responses. We hypothesize that these time-dependent relaxations of matrix should be mimicked in a synthetic matrix to modulate differentiation of mesenchymal stem cells into cartilage producing cells. To achieve this, our approach is to engineer amphiphilic polyurethanes as colloidal microgel which exhibits hierarchical microstructures to regulate viscoelasticity and poroelasticity in mutually exclusive manner and use these gels for chondrogenesis of mesenchymal stem cells. Amphiphilic polyurethanes can be engineered to form colloidal dispersion in aqueous medium which can be subsequently aggregated into gel under shear mode or quiescent (gravity) state. Segmental composition of amphiphilic polyurethanes can modulate viscoelastic response through relaxation of macromolecular chains of polymeric network and microstructure of colloidal gels modulates poroelastic diffusion through migration of solvent molecules. Viscoelasticity of colloidal gel matrix can modulate cell-matrix interactions while poroelastic effect can regulate cell-cell interactions during chondrogenesis of mesenchymal stem cells. Our goal is to design colloidal polyurethane gels where these two responses are tuned independently and assess the effect of matrix viscoelasticity and poroelasticity for chondrogenic differentiation. Furthermore, these stem cell seeded colloidal gels should exhibit shear- dependent self-healing character for minimally invasive transplantation as injectable gels. Through this application, we specifically propose to: (a) characterize the viscoelastic and poroelastic character of colloidal gels developed under shear induced and quiescent state from polyethylene glycol based amphiphilic polyurethanes and (b) analyze the chondrogenesis of mesenchymal stem cells within these gels to correlate the matrix relaxation effect with the differentiability of stem cells. Our long term goal is to establish polyurethane based colloidal gels as a tissue-engineered construct for cartilage defects and examine the efficacy of this approach through in vivo cartilage defect animal models. This proposed study presents a significant advancement in biomaterial based cartilage regeneration strategy and will present a therapeutically viable treatment option for arthritic cartilage.

 描述：退行性关节疾病的治疗对于软骨的结构和功能恢复仍然是一个巨大的挑战。基于生物材料合成基质的组织工程软骨提供了一种很有前途的方法，但目前的生物材料再生能力有限，因为这些材料不能模拟天然软骨基质的力学形态特征，表现出粘弹性和孔弹性反应。我们假设，这些依赖于时间的基质松弛应该在合成的基质中模拟，以调节间充质干细胞向软骨产生细胞的分化。为了实现这一点，我们的方法是将两亲性聚氨酯设计成胶体微凝胶，这种胶体微凝胶具有层次化的微结构，以相互排斥的方式调节粘弹性和孔弹性，并将这些凝胶用于间充质干细胞的软骨形成。两亲性聚氨酯可以在水介质中形成胶体分散体，然后在剪切模式或静态(重力)状态下凝聚成凝胶。两亲性聚氨酯的链段组成可以通过松弛聚合物网络的大分子链来调节粘弹性反应，胶体凝胶的微观结构通过溶剂分子的迁移来调节孔弹性扩散。在间充质干细胞的软骨形成过程中，胶体凝胶基质的粘弹性可以调节细胞-基质的相互作用，而孔弹性效应可以调节细胞-细胞的相互作用。我们的目标是设计胶体聚氨酯凝胶，其中这两种反应是独立调节的，并评估基质粘弹性和孔弹性对软骨分化的影响。此外，这些干细胞种植的胶体凝胶应该表现出剪切依赖的自愈特性，作为可注射凝胶用于微创移植。通过这一应用，我们特别提出：(A)表征聚乙二醇型两亲性聚氨酯在剪切诱导和静止状态下形成的胶体凝胶的粘弹性和孔弹性特征，以及(B)分析这些凝胶中间充质干细胞的软骨生成，以将基质松弛效应与干细胞的分化联系起来。我们的长期目标是建立基于聚氨酯的胶体凝胶作为软骨缺损的组织工程化构建，并通过体内软骨缺损动物模型来检验这种方法的效果。这项拟议的研究展示了基于生物材料的软骨再生策略的重大进展，并将为关节炎软骨提供一种治疗上可行的选择。