In this study, hyaluronic acid-pullulan injectable hydrogels were incorporated with biomimetic hydroxyapatite spheres and were modified using silane coupling agents in order to improve the physicochemical, mechanical, and biological performance of hydrogels. So the biomimetic hydroxyapatite spheres were synthesized through immersion of gelatin-siloxane microspheres in the simulated body fluid. The results of field emission scanning electron microscopy, energy dispersive X-ray spectroscopy, and X-ray diffraction spectra confirmed the formation of hydroxyapatite on the surface of hybrid spheres. The morphology observation of the prepared hydrogels confirmed the uniform distribution of hydroxyapatite spheres in gel structure. The chemical characterization proved the possible interactions between the polymers and the created complex with a silane coupling agent to provide more durability. Improvement of storage modulus and viscosity indicated the positive role of hydroxyapatite spheres on the stability and long-lasting durability of hydrogels. A slight reduction was observed in the absorption capacity and water retention in hybrid hydrogels; even though, the great resistance to enzymatic biodegradation led to higher durability of hydroxyapatite-contained gels. Improvement in L-929 fibroblast cell adhesion and spreading especially around the biomimetic hydroxyapatite spheres along with higher cell viability demonstrated the initial potential of hydrogels for further pre-clinical and clinical studies in order to recommend the gels for dermal rejuvenation applications.

在这项研究中，将透明质酸-普鲁兰可注射水凝胶与仿生羟基磷灰石球体混合，并使用硅烷偶联剂对其进行修饰，以改善水凝胶的物理化学，机械和生物学性能。因此，通过将明胶-硅氧烷微球浸入模拟体液中来合成仿生羟基磷灰石球。场发射扫描电子显微镜，能量色散X射线光谱和X射线衍射光谱的结果证实了混合球体表面上羟基磷灰石的形成。制备的水凝胶的形态观察证实了羟基磷灰石球在凝胶结构中的均匀分布。化学特性证明，聚合物与所生成的配合物之间存在可能的相互作用，并使用硅烷偶联剂提供了更高的耐久性。储能模量和粘度的改善表明羟基磷灰石球对水凝胶的稳定性和持久耐久性的积极作用。观察到杂化水凝胶的吸收能力和保水能力略有下降；即使如此，对酶促生物降解的强大抵抗力也使得含羟基磷灰石的凝胶具有更高的耐久性。L-929成纤维细胞粘附力的改善和尤其是在仿生羟基磷灰石球体周围的散布以及更高的细胞生存能力证明了水凝胶在进一步的临床前和临床研究中的初步潜力，以便为皮肤再生应用推荐该凝胶。