Wang Dalin, Qi Guangyan, Zhang Mingcai, Carlson Brandon, Gernon Matthew, Burton Douglas, Sun Xiuzhi Susan, Wang Jinxi
Department of Orthopedic Surgery, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
Department of Biological and Agricultural Engineering, Kansas State University, Seaton Hall, 919 Mid-Campus Drive North, Manhattan, KS 66506, USA.
J Funct Biomater. 2024 Dec 6;15(12):369. doi: 10.3390/jfb15120369.
This study aimed to investigate the impact of varying the formulation of a specific peptide hydrogel (PepGel) on the release kinetics of rhBMP-2 in vitro. Three PepGel formulations were assessed: (1) 50% / (peptides volume/total volume) PepGel, where synthetic peptides were mixed with crosslinking reagents and rhBMP-2 solution; (2) 67% / PepGel; (3) 80% / PepGel. Each sample was loaded with 12 µg of rhBMP-2 and incubated in PBS. Released rhBMP-2 was quantified by ELISA at 1 h, 6 h, and 1, 2, 4, 7, 10, 14, and 21 days. To explore how PepGel formulations influence rhBMP-2 release, the gel porosities, swelling ratios, and mechanical properties of the three PepGel formulations were quantitatively analyzed. The results showed that rhBMP-2 encapsulated with 50% / PepGel exhibited a sustained release over the 21-day experiment, while the 67% and 80% / PepGels demonstrated significantly lower rhBMP-2 release rates compared to the 50% formulation after day 7. Higher histological porosity of PepGel was significantly correlated with increased rhBMP-2 release rates. Conversely, the swelling ratio and elastic modulus of the 50% / PepGel were significantly lower than that of the 67% and 80% / formulations. In conclusion, this study indicates that varying the formulation of crosslinked PepGel can control rhBMP-2 release rates in vitro by modulating gel porosity, swelling ratio, and mechanical properties. Encapsulation with 50% / PepGel offers a sustained rhBMP-2 release pattern in vitro; if replicated in vivo, this could mitigate the adverse effects associated with burst release of rhBMP-2 in clinical applications.
本研究旨在调查改变特定肽水凝胶（PepGel）的配方对重组人骨形态发生蛋白-2（rhBMP-2）体外释放动力学的影响。评估了三种PepGel配方：（1）50% /（肽体积/总体积）PepGel，其中合成肽与交联剂和rhBMP-2溶液混合；（2）67% / PepGel；（3）80% / PepGel。每个样品加载12 μg rhBMP-2，并在磷酸盐缓冲液（PBS）中孵育。在1小时、6小时以及1、2、4、7、10、14和21天通过酶联免疫吸附测定（ELISA）对释放的rhBMP-2进行定量。为了探究PepGel配方如何影响rhBMP-2的释放，对三种PepGel配方的凝胶孔隙率、溶胀率和力学性能进行了定量分析。结果表明，在为期21天的实验中，用50% / PepGel包封的rhBMP-2呈现出持续释放，而在第7天后，67%和80% / PepGel的rhBMP-2释放速率明显低于50%配方。PepGel较高的组织学孔隙率与rhBMP-2释放速率增加显著相关。相反，50% / PepGel的溶胀率和弹性模量明显低于67%和80% /配方。总之，本研究表明，改变交联PepGel的配方可通过调节凝胶孔隙率、溶胀率和力学性能来控制rhBMP-2的体外释放速率。用50% / PepGel包封在体外提供了rhBMP-2的持续释放模式；如果在体内得到复制，这可能减轻临床应用中与rhBMP-2突发释放相关的不良反应。
