Hypoxia inducible factor regulating scaffolds for osteochondral regeneration

缺氧诱导因子调节骨软骨再生支架

• 批准号: 1820468
• 金额: --
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1820468
• 关键词: Hypoxia; inducible; factor; regulating; scaffolds

Acute cartilage lesions, which can cause disability and progress osteoarthritis , are a significant clinical problem. The poor self-hearing capacity of the cartilage has prompted strategies to repair damaged articulating surfaces with surgically-implantable, engineered osteochondral constructs that provide a fill thickness repair that seamlessly fuses with the subchondral bone. A major hurdle in creating engineered osteochondral tissue is in replicating the distinct microenvironmets of bone and cartilage in a single continuous construct. This interdisciplinary project takes a new approach to osteochondral regeneration by engineering materials that mimic the native osteochondral tissue by spatially controlling the cellular regulation of oxygen via hypoxia inducing factor (HIF) stabilisation. Our objective will be to utilise PEGDA/hyaluronan-based hydrogels, tissue-specific growth factors and of human mesenchymal stem cells (MSC) in a single, continuous construct. We will then use a combination of biological and materials engineering methods to assess region-specific bone and cartiliage tissue formation. Translational aspects will include testing constructs in an osteochondral defect in a small animal model. We aim to deliver a new tissue engineering strategy for osteochondral regeneration by mimicking the microenvironmental conditions of native tissue, particularly oxygen pressure, to develop successful therapies to treat cartilage lesions. An ambitious versatile student will gain skills i MSC isolation and culture, qRT-PCR, histochemical and immunostaining techniques, microCT, Raman spectroscopy and small animal surgery. Objectives: year1/2-incorporate HIF mimetic gradient into scaffolds, Year2/3-demonstrate osteochondral tissue reformation in vitro, Year3/4-animal model surgery and evaluation of healing.

急性软骨损伤是一个重要的临床问题，可导致残疾和骨关节炎的进展。软骨的较差的自我听觉能力已经促使采用可植入的工程化骨软骨结构来修复受损的关节表面的策略，该结构提供与软骨下骨无缝融合的填充厚度修复。制造工程化骨软骨组织的一个主要障碍是在一个连续的结构中复制骨和软骨的不同微结构。这个跨学科的项目采用了一种新的方法，通过工程材料模拟天然骨软骨组织，通过缺氧诱导因子（HIF）稳定化空间控制氧的细胞调节。我们的目标将是利用PEGDA/透明质酸为基础的水凝胶，组织特异性生长因子和人类间充质干细胞（MSC）在一个单一的，连续的结构。然后，我们将使用生物学和材料工程方法的组合来评估特定区域的骨和软骨组织形成。平移方面将包括在小动物模型中测试骨软骨缺损中的结构。我们的目标是通过模拟天然组织的微环境条件，特别是氧气压力，为骨软骨再生提供一种新的组织工程策略，以开发治疗软骨病变的成功疗法。一个雄心勃勃的多才多艺的学生将获得MSC分离和培养，qRT-PCR，组织化学和免疫染色技术，microCT，拉曼光谱和小动物手术的技能。目的：第1/2年-将HIF模拟梯度掺入支架中，第2/3年-体外证实骨软骨组织重建，第3/4年-动物模型手术和愈合评估。

项目成果

Local depletion of proteoglycans mediates cartilage tissue repair in an ex vivo integration model.

在离体整合模型中，蛋白聚糖的局部消耗介导软骨组织修复。

• DOI: 10.1016/j.actbio.2022.06.032
• 发表时间: 2022
• 期刊: Acta biomaterialia
• 影响因子: 9.7
• 作者: Merrild NG

Engineered hydrogels for mechanobiology.

• DOI: 10.1038/s43586-022-00179-7
• 发表时间: 2022-12-15
• 期刊: Nature reviews. Methods primers
• 作者: Blache U;Ford EM;Ha B;Rijns L;Chaudhuri O;Dankers PYW;Kloxin AM;Snedeker JG;Gentleman E
• 通讯作者: Gentleman E