Growth factor delivery using extracellular matrix-mimicking substrates for musculoskeletal tissue engineering and repair.
Growth factor delivery using extracellular matrix-mimicking substrates for musculoskeletal tissue engineering and repair.
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DOI：
10.1016/j.bioactmat.2020.12.012
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发表时间：
2021-07
影响因子：
18.9
通讯作者：
Leach JK
中科院分区：
文献类型：
--
作者：
Gresham RCH;Bahney CS;Leach JK
肌肉骨骼组织再生的治疗方法通常采用生长因子（GF）来影响邻近细胞并促进迁移、增殖或分化。尽管在临床前模型中取得了有希望的结果，但诱导生物大分子的使用在转化为临床方面取得的成功有限。该领域尚未充分克服诸如时空控制不佳和超生理剂量等重大障碍，这些障碍通常会导致有害的副作用。生物大分子的生理呈现和保留受到细胞外基质 (ECM) 的调节，细胞外基质通过静电相互作用充当 GF 的储存库。细胞外蛋白、脱细胞组织的操作以及一系列生物材料的合成 ECM 模拟应用的进展增加了指导 GF 呈现的能力。利用 ECM 模拟物的生物材料技术的成功应用可增加组织再生，而不依赖于诱导生物大分子的超生理剂量。这篇综述描述了使用 ECM 模拟基质来管理 GF 呈现的最新策略，以实现骨、软骨和肌肉的再生。综述了生长因子在内源性骨、软骨和肌肉形成和修复过程中的贡献。讨论了生长因子在临床应用中的应用和挑战。描述了生长因子的载体，重点是天然细胞外基质 (ECM) 及其成分。强调了生长因子输送的前沿。
Therapeutic approaches for musculoskeletal tissue regeneration commonly employ growth factors (GFs) to influence neighboring cells and promote migration, proliferation, or differentiation. Despite promising results in preclinical models, the use of inductive biomacromolecules has achieved limited success in translation to the clinic. The field has yet to sufficiently overcome substantial hurdles such as poor spatiotemporal control and supraphysiological dosages, which commonly result in detrimental side effects. Physiological presentation and retention of biomacromolecules is regulated by the extracellular matrix (ECM), which acts as a reservoir for GFs via electrostatic interactions. Advances in the manipulation of extracellular proteins, decellularized tissues, and synthetic ECM-mimetic applications across a range of biomaterials have increased the ability to direct the presentation of GFs. Successful application of biomaterial technologies utilizing ECM mimetics increases tissue regeneration without the reliance on supraphysiological doses of inductive biomacromolecules. This review describes recent strategies to manage GF presentation using ECM-mimetic substrates for the regeneration of bone, cartilage, and muscle. The contribution of growth factors during endogenous formation and repair of bone, cartilage, and muscle is reviewed. The application and challenges of growth factors in clinical applications is discussed. Carriers for growth factors are described, with an emphasis on the native extracellular matrix (ECM) and its constituents. Frontiers in growth factor delivery are highlighted.
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