Xu Jiazhu, Brown Jacob, Shaik Rubia, Soto-Garcia Luis, Liao Jun, Nguyen Kytai, Zhang Ge, Hong Yi
Department of Bioengineering, University of Texas at Arlington, Arlington, TX 76019, United States of America.
Department of Biomedical Engineering, The University of Akron, Akron, OH 44325, United States of America.
Biomater Adv. 2025 May;170:214203. doi: 10.1016/j.bioadv.2025.214203. Epub 2025 Jan 30.
Myocardial infarction (MI) is a predominant cause of morbidity and mortality globally. Therapeutic chemokines, such as stromal cell-derived factor 1α (SDF-1α), present a promising opportunity to treat the profibrotic remodeling post-MI if they can be delivered effectively to the injured tissue. However, direct injection of SDF-1α or physical entrapment in a hydrogel has shown limited efficacy. Here, we developed a sustained-release system consisting of SDF-1α loaded poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) and an injectable porcine cardiac decellularized extracellular matrix (cdECM) hydrogel. This system demonstrated a sustained release of SDF-1α over four weeks while there is one week release for SDF-1α directly encapsulated in the cdECM hydrogel during in vitro testing. The incorporation of PLGA NPs into the cdECM hydrogel significantly enhanced its mechanical properties, increasing the Young's modulus from 561 ± 228 kPa to 1007 ± 2 kPa and the maximum compressive strength from 639 ± 42 kPa to 1014 ± 101 kPa. This nanocomposite hydrogel showed good cell compatibility after 7 days of culture with H9C2 cells, while the released SDF-1α retained its bioactivity, as evidenced by its chemotactic effects in vitro. Furthermore, in vivo studies further highlighted its significant ability to promote angiogenesis in the infarcted area and improve cardiac function after intramyocardial injection. These results demonstrated the therapeutic potential of combining local release of SDF-1α with the cdECM hydrogel for MI treatment.
心肌梗死（MI）是全球发病和死亡的主要原因。治疗性趋化因子，如基质细胞衍生因子1α（SDF-1α），如果能够有效地递送至受损组织，将为治疗心肌梗死后的纤维化重塑提供一个有前景的机会。然而，直接注射SDF-1α或物理包埋于水凝胶中已显示出有限的疗效。在此，我们开发了一种缓释系统，该系统由负载SDF-1α的聚乳酸-乙醇酸共聚物纳米颗粒（PLGA NPs）和可注射的猪心脏脱细胞细胞外基质（cdECM）水凝胶组成。在体外测试期间，该系统显示SDF-1α持续释放四周，而直接包封于cdECM水凝胶中的SDF-1α释放一周。将PLGA NPs掺入cdECM水凝胶中显著增强了其机械性能，使杨氏模量从561±228 kPa增加到1007±2 kPa，最大抗压强度从639±42 kPa增加到1014±101 kPa。与H9C2细胞培养7天后，这种纳米复合水凝胶显示出良好的细胞相容性，同时释放的SDF-1α保留了其生物活性，这在体外趋化作用中得到了证实。此外，体内研究进一步突出了其在心肌内注射后促进梗死区域血管生成和改善心脏功能的显著能力。这些结果证明了将SDF-1α局部释放与cdECM水凝胶相结合用于治疗心肌梗死的治疗潜力。
