Self Sustaining Scaffolds

随着生物材料科学的发展，发展了非常简单的分类，如生物惰性、生物活性或可生物可吸收的，以与溶解度有关的分类。许多令人着迷的材料--最初被归类为“生物活性”的组织相互作用--从未被解释过，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认为是人工制品，虽然可重现，但人们并不了解。我们提出，简单陶瓷配方诱导成骨的原因必须是离子的，这引发了许多关于钙和磷离子控制如何改变骨修复的论文。申请人最近发现，大直径的血管可以被诱导萌发，形成新的血管树，可以为全新的体积充氧。这些血管直径为1毫米，因此可以被切断并重新连接到身体其他部位的动脉上，从而克服了组织重建的巨大障碍。将诱导材料的范围扩大到骨以外是很重要的，因为它表明了一种更普遍的效果和开发修复技术的新途径。基于先前发现基金资助的研究，申请者构思了可以接管血管系统的一些功能、局部充氧和解毒缺血组织的材料。问题看起来很简单：供应氧气、营养物质和清除废物。然而，在正确的时间以正确的数量完成这项工作需要以与现有工作流兼容的形式开发多种材料构造。这是具有挑战性的；需要识别和了解要修改的参数，而不改变材料的其他释放或吸附曲线，并与无毒性或完全再吸收的要求所划定的狭窄边界保持一致。在一项初步的概念验证研究中，申请人成功地防止了血管形成不良的伤口的坏死。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是极具挑战性的。虽然可以产生能够再生肌肉的细胞，但没有技术可以在植入后将它们维持足够长的时间以进行再生。在这一应用中，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结构，这些组织结构可以在没有血管的情况下存活足够长的时间，以度过植入后的初始炎症和再愈合阶段。能够在大的3D体积中创建细胞结构，消除了设计全组织类似物的障碍之一。该提案涉及确定以生物材料为基础的组织维持微环境控制的机制和限制，以实现这一目标。

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.