Tang Qian, Lim Thou, Wei Xiao-Juan, Wang Qi-Yang, Xu Jian-Chen, Shen Li-Yan, Zhu Zhen-Zhong, Zhang Chang-Qing
Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
Biomaterials. 2020 Oct;255:120138. doi: 10.1016/j.biomaterials.2020.120138. Epub 2020 May 22.
Great efforts have been made to develop suitable bioactive constructs that release growth factors (GFs) in a controlled manner for tissue-regeneration applications. Platelet lysates (PLs) are an affordable source of multiple GFs and other proteins, and show great potential in the wound-healing process. Herein, poly-l-lysine (PLL) and hyaluronic acid (HA) were applied to build free-standing polyelectrolyte multilayer films (PEMs) using the PH-amplified layer-by-layer self-assembly method. Molecular simulations were performed, which showed that in the end layer of PEMs, HA was more attractive to PLs than was PLL. The HA/PLL films constructed with or without 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride (EDC) cross-linking both absorbed PLs successfully, exhibiting high hydrophilicity and GF absorptivity. The release profile of the EDC30 film lasted up to 2 weeks, and PL-loaded films supported cell proliferation, adhesion, migration, and angiogenesis in vitro. Moreover, due to sustained delivery of PLs, the membranes (especially the crosslinked film) helped to promote granulation-tissue formation, collagen deposition, and neovascularization in the region of the defect, resulting in rapid re-epithelialization and regeneration of skin. Mechanistically, the beneficial effects of a PL-loaded PEM coating might be related to activation of the hypoxia-inducible factor-1(Hif-1α)/vascular endothelial growth factor (VEGF) axis. As an off-the-shelf and cell-free treatment option, these biomimetic multilayers have great potential for use in the fabrication of devices that allow stable incorporation of PLs, thereby exerting synergistic effects for efficient wound healing.
人们已经做出了巨大努力来开发合适的生物活性构建体，以便以可控方式释放生长因子（GFs）用于组织再生应用。血小板裂解物（PLs）是多种生长因子和其他蛋白质的廉价来源，并且在伤口愈合过程中显示出巨大潜力。在此，使用pH放大的逐层自组装方法，将聚-L-赖氨酸（PLL）和透明质酸（HA）应用于构建独立的聚电解质多层膜（PEMs）。进行了分子模拟，结果表明在PEMs的最外层，HA对PLs的吸引力比PLL更大。无论有无1-乙基-3-[3-二甲基氨基丙基]碳二亚胺盐酸盐（EDC）交联构建的HA/PLL膜都成功吸收了PLs，表现出高亲水性和GF吸收性。EDC30膜的释放曲线持续长达2周，负载PL的膜在体外支持细胞增殖、粘附、迁移和血管生成。此外，由于PLs的持续递送，这些膜（尤其是交联膜）有助于促进缺损区域的肉芽组织形成、胶原蛋白沉积和新血管形成，从而导致皮肤快速再上皮化和再生。从机制上讲，负载PL的PEM涂层的有益效果可能与缺氧诱导因子-1（Hif-1α）/血管内皮生长因子（VEGF）轴的激活有关。作为一种现成的无细胞治疗选择，这些仿生多层膜在制造能够稳定掺入PLs的装置方面具有巨大潜力，从而发挥协同作用以实现高效伤口愈合。
