Self Sustaining Scaffolds

自持式脚手架

• 批准号: RGPIN-2019-05270
• 负责人: Barralet, Jake
• 金额: $ 2.84万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=738160
• 关键词: Self; Sustaining; Scaffolds

As biomaterials science evolved very simple classifications such as bioinert, bioactive or bioresorbable were developed to categorise them related to solubility. Many fascinating materials-tissue interactions originally classified as `bioactive' were never explained, in particular tissue inductive materials. Materials that induced bone to form in soft tissues were initially observed as artifacts and while reproducible were not understood. We proposed that the cause of osteoinduction by simple ceramic formulations must be ionic in origin and this gave rise to many papers illustrating how calcium and phosphate ion control could alter bone repair.  The applicant recently discovered that large diameter blood vessels could be induced to sprout and form new vascular trees that can oxygenate entirely new volumes. These vessels are 1 mm in diameter and so can be cut off and reattached to an artery elsewhere in the body, thereby overcoming a huge impediment to tissue reconstruction. The broadening of the scope of inductive materials beyond bone is important as it indicates a more general effect and a new way to develop repair technologies. Based on prior discovery grant supported research, the applicant conceived materials that could take over some of the functions of the vasculature, locally oxygenating and detoxifying ischemic tissues. The problem is deceptively simple: supply oxygen, nutrients and remove waste. However, doing this at the right time in the right amount requires development of multiple material constructs in forms that are compatible with existing work flow. This is challenging; requiring an identification and understanding of the parameter to be modified without altering the other release or adsorption profiles of the materials and keeping with the narrow boundaries delineated by the requirement of non-toxicity or complete resorption. The applicant has succeeded in preventing necrosis in poorly vascularized wounds in a pilot proof of concept study. He has in the past year extended this to injectable forms that can prevent secondary necrosis in skin. Muscle is extremely challenging to preserve or regenerate without a blood supply. While cells capable of muscle regeneration can be produced, no technology exists to sustain them inside after implantation long enough for regeneration to occur. Using our approach we can sustain cell viability at 1-2 x 108 cells/ml. In this application, we will develop bioinks based on our approach to sustain and temporarily immuno-isolate myoblasts as living tissue constructs that can survive without vasculature long enough to survive the initial inflammation and revascualrisation phase following implantation. Being able to create cell constructs in large 3D volumes eliminates one of the obstacles to engineering full tissue analogues. The proposal is concerned with determining mechanisms and limits to biomaterials-based control of tissue sustaining microenvironments in order to achieve this.

随着生物材料科学的发展，开发了非常简单的分类，如生物惰性，生物活性或生物可吸收，以将其与溶解度相关。许多最初被归类为“生物活性”的迷人材料-组织相互作用从未得到解释，特别是组织诱导材料。诱导骨在软组织中形成的材料最初被观察为伪影，虽然可重现，但尚不清楚。我们提出，简单陶瓷配方的骨诱导原因必须是离子起源，这引起了许多论文，说明如何钙和磷酸盐离子控制可以改变骨修复。申请人最近发现，大直径血管可以诱导发芽，形成新的血管树，可以覆盖全新的体积。这些血管直径为1毫米，因此可以切断并重新连接到身体其他部位的动脉，从而克服组织重建的巨大障碍。将感应材料的范围扩大到骨以外是重要的，因为它表明了更普遍的效果和开发修复技术的新方法。基于先前的发现补助金支持的研究，申请人构思了可以接管脉管系统的一些功能、局部充氧和解毒缺血组织的材料。问题看似简单：提供氧气、营养和清除废物。然而，在正确的时间以正确的数量这样做需要以与现有工作流程兼容的形式开发多种材料结构。这是具有挑战性的;需要在不改变材料的其它释放或吸附曲线的情况下识别和理解待修改的参数，并保持由无毒性或完全再吸收的要求所划定的窄边界。 申请人在一项初步概念验证研究中成功预防了血管化不良伤口的坏死。在过去的一年里，他将其扩展到可以预防皮肤继发性坏死的注射形式。肌肉在没有血液供应的情况下保存或再生极具挑战性。虽然能够产生肌肉再生的细胞，但没有技术可以在植入后维持它们足够长的时间以使再生发生。使用我们的方法，我们可以将细胞活力维持在1-2 x 108个细胞/ml。在本申请中，我们将基于我们的方法开发生物墨水，以维持和暂时免疫隔离成肌细胞作为活组织构建体，其可以在没有脉管系统的情况下存活足够长的时间，以在植入后的初始炎症和血管重建阶段存活。能够在大的3D体积中创建细胞构建体消除了工程化完整组织类似物的障碍之一。该提案涉及确定基于生物材料的组织维持微环境控制的机制和限制，以实现这一目标。