Bioprosthetic cornea: using polymeric templates for directed stem cell growth

生物假体角膜:使用聚合物模板进行干细胞定向生长

基本信息

  • 批准号:
    BB/I008187/1
  • 负责人:
  • 金额:
    $ 83.38万
  • 依托单位:
  • 依托单位国家:
    英国
  • 项目类别:
    Research Grant
  • 财政年份:
    2011
  • 资助国家:
    英国
  • 起止时间:
    2011 至 无数据
  • 项目状态:
    已结题

项目摘要

The cornea is our window to the world, once compromised by wounding, disease or age, a loss of vision results. By improving our understanding of corneal structure and providing new methods of corneal transplantation the sight of many more patients can be restored. Currently, corneal transplantation requires a continuous supply of healthy donor corneas. However worldwide demand has grown and taken together with an aging population and the rapid rise in laser eye surgery (which can negatively affect the donor tissue suitability for transplantation) the search for an effective engineered replacement is essential if current levels of corneal transplantation are to be maintained. This investigation stems from our previous work in understanding the molecular structure underpinning corneal transparency, the development of novel corneal biomaterials and the limitations of the current corneal stem cell transplantation techniques, specifically the materials used to grow and convey the stem cells to the patient. Previously, we have quantified the nanostructure of the cornea and related this structure to the preservation of corneal transparency; furthermore we have applied these measurements to the design of new corneal biomaterials capable of supporting corneal epithelial stem cell differentiation and growth. Therefore, we will draw on our knowledge of corneal structure, corneal stem cell isolation and cultivation and novel biomaterials to engineer a tissue suitable for corneal transplantation. To do this we will develop a template made from tractable regularly spaced aligned polymers (reflecting the natural state of corneal nanostructure). The template will contain protein fragments recognisable by the human corneal stem cells enabling them to attach in a highly ordered and controlled manner. Once attached the cells will be chemically induced to differentiate and produce collagen fibres. The alignment of these fibres will be guided by the cells orientation. The template will then slowly lose its integrity and detach from the cells by way of enzymes released by the corneal cells, thus releasing the aligned collagen as a tissue engineered collagen mat. These mats will then be stacked and compressed to produce a robust biomaterial made solely from human proteins (mostly collagen), the polymer template having been removed during processing. The biomaterials mechanical strength and ability to support corneal epithelial growth upon its surface will then be tested. We have already shown that compressed mats of rat tail collagen are both mechanically robust as well as excellent substrates for corneal epithelial cell growth. This work represents a significant step forward in the development of biomaterials. Instead of designing and using bio-compatible polymers to represent tissue for transplantation our approach is to use the polymers merely as a template allowing the cells to produce the actual biomaterial. Furthermore, since the template is easily discarded the cell based biomaterial represents the ultimate in biocompatibility as it is comprised of human proteins possibly even derived from cells taken from the patient's own body. The beneficiaries of this work would be those working in the fields of polymer chemistry as the development of aligned polymers containing protein fragments that are both recognised and degraded by cells is not trivial. Scientists in the blossoming field of biomaterials would be given a new direction in the development of truly bio-compatible materials (i.e. ones derived from stem cells). Tissue engineers would be given a new tool with which they could create similar stem cell based materials for bone, skin etc. repair and finally ocular regenerative medicine would benefit from the development of a replacement human donor corneal tissue.
角膜是我们通向世界的窗口,一旦受到伤害、疾病或年龄的损害,就会导致视力丧失。通过提高对角膜结构的认识和提供新的角膜移植方法,可以使更多的患者恢复视力。目前,角膜移植需要持续供应健康的供体角膜。然而,随着人口老龄化和激光眼科手术(会对供体组织移植的适宜性产生负面影响)的快速增长,世界范围内的需求不断增长,如果要维持目前的角膜移植水平,寻找有效的工程替代是必不可少的。这项研究源于我们之前的工作,了解支持角膜透明度的分子结构,新型角膜生物材料的发展以及当前角膜干细胞移植技术的局限性,特别是用于生长和向患者输送干细胞的材料。之前,我们已经量化了角膜的纳米结构,并将这种结构与角膜透明度的保存联系起来;此外,我们还将这些测量结果应用于设计能够支持角膜上皮干细胞分化和生长的新型角膜生物材料。因此,我们将利用我们在角膜结构,角膜干细胞分离和培养以及新型生物材料方面的知识来设计适合角膜移植的组织。为了做到这一点,我们将开发一种模板,由易于处理的规则间隔排列的聚合物(反映角膜纳米结构的自然状态)制成。该模板将包含人类角膜干细胞可识别的蛋白质片段,使它们能够以高度有序和可控的方式附着。一旦附着,细胞将被化学诱导分化并产生胶原纤维。这些纤维的排列将由细胞的方向来引导。然后,模板将慢慢失去其完整性,并通过角膜细胞释放的酶从细胞中分离出来,从而释放出排列整齐的胶原蛋白,作为组织工程胶原蛋白垫。然后,这些垫将被堆叠和压缩,以产生仅由人类蛋白质(主要是胶原蛋白)制成的坚固的生物材料,聚合物模板在加工过程中被移除。生物材料的机械强度和支持角膜上皮生长的能力将在其表面进行测试。我们已经证明,大鼠尾部胶原蛋白压缩垫既具有机械强度,又具有良好的角膜上皮细胞生长基质。这项工作代表了生物材料发展的重要一步。而不是设计和使用生物相容性聚合物来代表移植组织,我们的方法是使用聚合物仅仅作为一个模板,允许细胞产生实际的生物材料。此外,由于模板很容易被丢弃,基于细胞的生物材料代表了最终的生物相容性,因为它由人类蛋白质组成,甚至可能来自患者自身的细胞。这项工作的受益者将是那些在聚合物化学领域工作的人,因为含有被细胞识别和降解的蛋白质片段的排列聚合物的发展不是微不足道的。在蓬勃发展的生物材料领域,科学家们将在开发真正的生物相容性材料(即来自干细胞的材料)方面获得新的方向。组织工程师将获得一种新的工具,利用这种工具,他们可以创造出类似的基于干细胞的材料,用于骨骼、皮肤等的修复。最终,眼部再生医学将受益于替代人类捐献角膜组织的发展。

项目成果

期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Self-assembly and bioactivity of a polymer/peptide conjugate containing the RGD cell adhesion motif and PEG
  • DOI:
    10.1016/j.eurpolymj.2013.02.016
  • 发表时间:
    2013-10-01
  • 期刊:
  • 影响因子:
    6
  • 作者:
    Castelletto, Valeria;Gouveia, Ricardo J.;Hamley, Ian W.
  • 通讯作者:
    Hamley, Ian W.
Application of retinoic acid improves form and function of tissue engineered corneal construct.
视黄酸的应用改善了组织工程角膜结构的形式和功能。
  • DOI:
    10.1080/15476278.2015.1093267
  • 发表时间:
    2015
  • 期刊:
  • 影响因子:
    2.3
  • 作者:
    Abidin FZ;Gouveia RM;Connon CJ
  • 通讯作者:
    Connon CJ
Tuning chelation by the surfactant-like peptide A6H using predetermined pH values.
  • DOI:
    10.1021/bm401640j
  • 发表时间:
    2014-02-10
  • 期刊:
  • 影响因子:
    6.2
  • 作者:
    Castelletto, V.;Hamley, I. W.;Segarra-Maset, M. D.;Berdugo Gumbau, C.;Miravet, J. F.;Escuder, B.;Seitsonen, J.;Ruokolainen, J.
  • 通讯作者:
    Ruokolainen, J.
Slow-Release RGD-Peptide Hydrogel Monoliths
  • DOI:
    10.1021/la302071e
  • 发表时间:
    2012-08-28
  • 期刊:
  • 影响因子:
    3.9
  • 作者:
    Castelletto, Valeria;Hamley, Ian W.;Connon, Che
  • 通讯作者:
    Connon, Che
The mechanical properties of amniotic membrane influence its effect as a biomaterial for ocular surface repair
  • DOI:
    10.1039/c2sm26175h
  • 发表时间:
    2012-01-01
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
    Chen, Bo;Jones, Roanne R.;Connon, Che J.
  • 通讯作者:
    Connon, Che J.
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Che Connon其他文献

Che Connon的其他文献

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{{ truncateString('Che Connon', 18)}}的其他基金

Development of Brillouin Spectroscopy for Mechanotransduction Research
用于力传导研究的布里渊光谱学的发展
  • 批准号:
    BB/N021576/1
  • 财政年份:
    2016
  • 资助金额:
    $ 83.38万
  • 项目类别:
    Research Grant
Bioprosthetic cornea: using polymeric templates for directed stem cell growth
生物假体角膜:使用聚合物模板进行干细胞定向生长
  • 批准号:
    BB/I008187/2
  • 财政年份:
    2014
  • 资助金额:
    $ 83.38万
  • 项目类别:
    Research Grant
Modulation of limbal niche stiffness to regulate stem cell differentiation
调节角膜缘生态位硬度以调节干细胞分化
  • 批准号:
    MR/K017217/2
  • 财政年份:
    2014
  • 资助金额:
    $ 83.38万
  • 项目类别:
    Research Grant
Investigation of optimal gel conditions for stem cell preservation at room temperature and scaling up of selected methodology
研究室温下保存干细胞的最佳凝胶条件并扩大所选方法的规模
  • 批准号:
    BB/K011111/2
  • 财政年份:
    2014
  • 资助金额:
    $ 83.38万
  • 项目类别:
    Research Grant
Modulation of limbal niche stiffness to regulate stem cell differentiation
调节角膜缘生态位硬度以调节干细胞分化
  • 批准号:
    MR/K017217/1
  • 财政年份:
    2013
  • 资助金额:
    $ 83.38万
  • 项目类别:
    Research Grant
Investigation of optimal gel conditions for stem cell preservation at room temperature and scaling up of selected methodology
研究室温下保存干细胞的最佳凝胶条件并扩大所选方法的规模
  • 批准号:
    BB/K011111/1
  • 财政年份:
    2013
  • 资助金额:
    $ 83.38万
  • 项目类别:
    Research Grant
Cold chain storage and distribution of therapeutic mammalian cell cultures including stem cells using sol-gel technology
使用溶胶凝胶技术冷链储存和分配包括干细胞在内的治疗性哺乳动物细胞培养物
  • 批准号:
    BB/I00985X/1
  • 财政年份:
    2011
  • 资助金额:
    $ 83.38万
  • 项目类别:
    Research Grant
Therapeutic corneal stem cell delivery using hydrogels without the need for ex vivo expansion
使用水凝胶进行治疗性角膜干细胞递送,无需离体扩增
  • 批准号:
    G0900877/1
  • 财政年份:
    2010
  • 资助金额:
    $ 83.38万
  • 项目类别:
    Research Grant
A tissue engineered corneal epithelium replacement for animal testing using human stem cells
使用人类干细胞进行动物试验的组织工程角膜上皮替代物
  • 批准号:
    BB/F019742/1
  • 财政年份:
    2008
  • 资助金额:
    $ 83.38万
  • 项目类别:
    Research Grant

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