Blond McIndoe Laboratories, Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, M13 9PL, UK.
School of Materials & Manchester Institute of Biotechnology, Faculty of Science and Engineering, University of Manchester, Manchester, M13 9PL, UK.
Adv Healthc Mater. 2019 Sep;8(17):e1900410. doi: 10.1002/adhm.201900410. Epub 2019 Jul 26.
Despite advances in microsurgical techniques, treatment options to restore prior function following peripheral nerve injury remain unavailable, and autologous nerve grafting remains the therapy of choice. Recent experimental work has focused on the development of artificial constructs incorporating smart biomaterials and stem cells, aspiring to match/improve the outcomes of nerve autografting. Chemically stimulated human adipose-derived stem cells (dhASC) can improve nerve regeneration outcomes; however, these properties are lost when chemical stimulation is withdrawn, and survival rate upon transplantation is low. It is hypothesized that interactions with synthetic hydrogel matrices could maintain and improve neurotrophic characteristics of dhASC. dhASC are cultured on PeptiGel-Alpha 1 and PeptiGel-Alpha 2 self-assembling peptide hydrogels, showing comparable viability to collagen I control gels. Culturing dhASC on Alpha 1 and Alpha 2 substrates allow the maintenance of neurotrophic features, such as the expression of growth factors and neuroglial markers. Both Alpha 1 and Alpha 2 substrates are suitable for the culture of peripheral sensory neurons, permitting sprouting of neuronal extensions without the need of biological extracellular matrices, and preserving neuronal function. PeptiGel substrates loaded with hdASC are proposed as promising candidates for the development of tissue engineering therapies for the repair of peripheral nerve injuries.
尽管显微外科技术取得了进步，但仍缺乏可用于恢复外周神经损伤后原有功能的治疗选择，自体神经移植仍然是首选疗法。最近的实验工作集中在开发包含智能生物材料和干细胞的人工构建体上，旨在匹配/改善神经自体移植的效果。化学刺激的人脂肪来源干细胞（dhASC）可以改善神经再生的效果；然而，当停止化学刺激时，这些特性就会丧失，移植后的存活率也很低。据推测，与合成水凝胶基质的相互作用可以维持和提高 dhASC 的神经营养特性。dhASC 在 PeptiGel-Alpha 1 和 PeptiGel-Alpha 2 自组装肽水凝胶上培养，其活力与胶原蛋白 I 对照凝胶相当。在 Alpha 1 和 Alpha 2 基质上培养 dhASC 可以维持神经营养特性，如生长因子和神经胶质标志物的表达。两种 Alpha 1 和 Alpha 2 基质都适合培养周围感觉神经元，允许神经元延伸的生长，而不需要生物细胞外基质，并保持神经元功能。负载 dhASC 的 PeptiGel 基质被提议作为开发用于修复周围神经损伤的组织工程治疗的有前途的候选物。
