Combat Wound Care, US Army Institute of Surgical Research, JBSA Fort Sam Houston, San Antonio, TX 78234, USA.
KeraNetics, Inc., Winston-Salem, NC 27101, USA.
Int J Mol Sci. 2022 Apr 7;23(8):4100. doi: 10.3390/ijms23084100.
One of the promising approaches to facilitate healing and regenerative capacity includes the application of growth-factor-loaded biomaterials. Human platelet lysate (hPL) derived from platelet-rich plasma through a freeze-thaw process has been used as a growth factor rich therapeutic in many regenerative applications. To provide sustained local delivery of the hPL-derived growth factors such as epidermal growth factor (EGF), the hPL can be loaded into biomaterials that do not degrade rapidly in vivo. Keratin (KSO), a strong filamentous protein found in human hair, when formulated as a hydrogel, is shown to sustain the release of drugs and promote wound healing. In the current study, we created a KSO biomaterial that spontaneously forms a hydrogel when rehydrated with hPL that is capable of controlled and sustained release of pro-regenerative molecules. Our study demonstrates that the release of hPL is controlled by changing the KSO hydrogel and hPL-loading concentrations, with hPL loading concentrations having a greater effect in changing release profiles. In addition, the 15% KSO concentration proved to form a stable hydrogel, and supported cell proliferation over 3 days without cytotoxic effects in vitro. The hPL-loaded keratin hydrogels show promise in potential applications for wound healing with the sustained release of pro-regenerative growth factors with easy tailoring of hydrogel properties.
一种有前景的促进愈合和再生能力的方法包括应用负载生长因子的生物材料。通过冻融过程从富含血小板的血浆中提取的人血小板裂解物(hPL)已被用作许多再生应用中的富含生长因子的治疗剂。为了提供 hPL 衍生的生长因子(如表皮生长因子 [EGF])的持续局部递送,可以将 hPL 加载到在体内不会快速降解的生物材料中。角蛋白(KSO)是一种存在于人类头发中的强丝状蛋白,当制成水凝胶时,可维持药物的释放并促进伤口愈合。在当前的研究中,我们创建了一种 KSO 生物材料,当用 hPL 重新水合时,它会自发形成水凝胶,能够控制和持续释放促再生分子。我们的研究表明,通过改变 KSO 水凝胶和 hPL 加载浓度来控制 hPL 的释放,而 hPL 加载浓度对改变释放曲线的影响更大。此外,15%的 KSO 浓度被证明可以形成稳定的水凝胶,并且在体外没有细胞毒性作用的情况下支持细胞增殖超过 3 天。负载 hPL 的角蛋白水凝胶具有在伤口愈合方面潜在应用的前景,具有持续释放促再生生长因子的能力,并且易于调整水凝胶特性。