Regenerative biomaterial patches for failing hearts

用于衰竭心脏的再生生物材料贴片

• 批准号: MR/S034757/1
• 负责人: Adam Celiz
• 金额: $ 155.69万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FS034757%2F1
• 关键词: Regenerative; biomaterial; patches; failing; hearts

Regenerative medicine has been established as a powerful approach to repair and restore tissue function and has facilitated the development of a new era of medical procedures and healthcare technologies including the delivery of stem cells. However, many of these technologies have failed to reach the clinic due to poor methods of cell delivery which lead to rapid cell death or poor engraftment with the target tissues intended for repair. To improve clinical outcomes, biomaterials have been developed with the aim to control cell delivery in sustained and localised manner. However, biomaterials currently under investigation are not able to adhere to target tissues and rely on sutures to hold them in place which induces further tissue damage and inflammation. Furthermore, a mechanical demanding environment such as beating heart requires the biomaterial to be robust and able to conform to the dynamic nature of the tissue. For example, myocardial infarction can lead to the death of 1 billion cardiomyoctes and cell-delivery to infarcted hearts is an emerging therapy to heal the diseased cardiac tissue. However, the efficacy of these treatments has been limited due to the lack of advanced cell-delivery methods.The overall goal of this research is to improve clinical outcomes associated with regenerative cell-based therapies by using advanced biomaterials as cell-delivery vehicles. This project aims to provide advanced biomaterials for regenerative medicine by delivering cardiac cells to diseased tissue via adhesive hydrogel patches. Such an approach would provide opportunities and have significant impact in fields such as biomaterials, regenerative medicine, drug delivery, medical devices and tissue engineering.The specific biomaterials that will be developed to deliver cells are hydrogels which are high-water content swollen gels. Hydrogels are a highly desirable class of materials to encapsulate cells as they can be synthesised to mimic natural tissues which increases the biocompatibility of these systems. Furthermore, the hydrogels can provide information to the encapsulated cells to encourage tissue-specific cell differentiation prior to delivery to the target diseased tissue.The hydrogels developed in this research are highly stretchable, so they can be deployed in physical demanding environments, and tissue adhesive which allows the encapsulated cells to closely interface with the tissue surface and be delivered more efficiently.The outcomes of this research would open up new opportunities for regenerative medicine as these hydrogels could significantly increase the efficiency of cell-based therapies, improve our treatment methods and understanding of diseased tissues and introduce innovative cell-laden biomaterials to the clinic as regenerative medical devices.

再生医学已被确立为修复和恢复组织功能的强大方法，并促进了医疗程序和医疗保健技术（包括干细胞输送）新时代的发展。然而，这些技术中的许多未能到达临床，这是由于差的细胞递送方法导致细胞快速死亡或与用于修复的靶组织的植入不良。为了改善临床结果，已经开发了生物材料，目的是以持续和局部的方式控制细胞递送。然而，目前正在研究的生物材料不能粘附到靶组织上，并且依赖于缝线将它们保持在适当位置，这会引起进一步的组织损伤和炎症。此外，诸如跳动的心脏的机械要求高的环境要求生物材料是坚固的并且能够符合组织的动态性质。例如，心肌梗塞可导致10亿个心肌细胞死亡，并且向梗塞心脏递送细胞是治愈患病心脏组织的新兴疗法。然而，由于缺乏先进的细胞递送方法，这些治疗的疗效受到限制。本研究的总体目标是通过使用先进的生物材料作为细胞递送载体来改善与基于再生细胞的治疗相关的临床结果。该项目旨在通过粘合水凝胶贴片将心脏细胞输送到病变组织，为再生医学提供先进的生物材料。这种方法将为生物材料、再生医学、药物递送、医疗器械和组织工程等领域提供机会并产生重大影响。将开发用于递送细胞的特定生物材料是水凝胶，其是高含水量的溶胀凝胶。水凝胶是封装细胞的一类非常理想的材料，因为它们可以合成以模拟天然组织，这增加了这些系统的生物相容性。此外，水凝胶可以向包封的细胞提供信息，以促进组织特异性细胞分化，然后递送到目标病变组织。本研究中开发的水凝胶具有高度可拉伸性，因此它们可以部署在物理要求苛刻的环境中，和组织粘合剂，使包裹的细胞与组织表面紧密接触，并更有效地输送。这项研究的结果将这为再生医学开辟了新的机会，因为这些水凝胶可以显著提高基于细胞的治疗的效率，改善我们的治疗方法和对患病组织的理解，并将创新的载有细胞的生物材料作为再生医疗器械引入临床。

项目成果

High-Throughput Screening of Thiol-ene Click Chemistries for Bone Adhesive Polymers.

对骨粘合剂聚合物的硫醇 - 二烯的高通量筛选。

• DOI: 10.1021/acsami.3c12072
• 发表时间: 2023-10-31
• 期刊: ACS APPLIED MATERIALS & INTERFACES
• 影响因子: 9.5
• 作者: Ganabady, Kavya;Negrini, Nicola Contessi;Scherba, Jacob C.;Nitschke, Brandon M.;Alexander, Morgan R.;Vining, Kyle H.;Grunlan, Melissa A.;Mooney, David J.;Celiz, Adam D.
• 通讯作者: Celiz, Adam D.

A biomechanical testing method to assess tissue adhesives for annulus closure

• DOI: 10.1016/j.jmbbm.2022.105150
• 发表时间: 2022-03-08
• 期刊: JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS
• 影响因子: 3.9
• 作者: Caldeira, Joana;Celiz, Adam;Newell, Nicolas
• 通讯作者: Newell, Nicolas

Scaffold-based developmental tissue engineering strategies for ectodermal organ regeneration.

• DOI: 10.1016/j.mtbio.2021.100107
• 发表时间: 2021-03
• 期刊: Materials today. Bio
• 作者: Contessi Negrini N;Angelova Volponi A;Higgins CA;Sharpe PT;Celiz AD
• 通讯作者: Celiz AD

Tunable Cross-Linking and Adhesion of Gelatin Hydrogels via Bioorthogonal Click Chemistry

• DOI: 10.1021/acsbiomaterials.1c00136
• 发表时间: 2021-06-04
• 期刊: ACS BIOMATERIALS SCIENCE & ENGINEERING
• 影响因子: 5.8
• 作者: Negrini, Nicola Contessi;Volponi, Ana Angelova;Celiz, Adam D.
• 通讯作者: Celiz, Adam D.