Department of Reproductive Medicine, Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; Laboratory of Key Technology and Materials in Minimally Invasive Spine Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Biomaterials. 2024 Sep;309:122615. doi: 10.1016/j.biomaterials.2024.122615. Epub 2024 May 11.
Enhancing the effectiveness of platelet-rich plasma (PRP) for endometrial regeneration is challenging, due to its limited mechanical properties and burst release of growth factors. Here, we proposed an injectable interpenetrating dual-network hydrogel that can locationally activate PRP within the uterine cavity, sustained release growth factors and further address the insufficient therapeutic efficacy. Locational activation of PRP is achieved using the dual-network hydrogel. The phenylboronic acid (PBA) modified methacrylated hyaluronic acid (HAMA) dispersion chelates Ca by carboxy groups and polyphenol groups, and in situ crosslinked with PRP-loaded polyvinyl alcohol (PVA) dispersion by dynamic borate ester bonds thus establishing the soft hydrogel. Subsequently, in situ photo-crosslinking technology is employed to enhance the mechanical performance of hydrogels by initiating free radical polymerization of carbon-carbon double bonds to form a dense network. The PRP-hydrogel significantly promoted the endometrial cell proliferation, exhibited strong pro-angiogenic effects, and down-regulated the expression of collagen deposition genes by inhibiting the TGF-β1-SMAD2/3 pathway in vitro. In vivo experiments using a rat intrauterine adhesion (IUA) model showed that the PRP-hydrogel significantly promoted endometrial regeneration and restored uterine functionality. Furthermore, rats treated with the PRP-hydrogel displayed an increase in the number of embryos, litter size, and birth rate, which was similar to normal rats. Overall, this injectable interpenetrating dual-network hydrogel, capable of locational activation of PRP, suggests a new therapeutic approach for endometrial repair.
提高富含血小板的血浆（PRP）治疗子宫内膜再生的效果具有挑战性，因为其机械性能有限且生长因子的释放呈爆发式。在这里，我们提出了一种可注射的互穿双网络水凝胶，可在子宫腔内定位激活 PRP，持续释放生长因子，并进一步解决治疗效果不足的问题。通过双网络水凝胶实现 PRP 的定位激活。苯硼酸（PBA）修饰的甲基丙烯酰化透明质酸（HAMA）分散体通过羧基和多酚基团螯合 Ca，与负载 PRP 的聚乙烯醇（PVA）分散体通过动态硼酸酯键原位交联，从而建立软水凝胶。随后，通过引发碳碳双键的自由基聚合来原位光交联技术增强水凝胶的机械性能，从而形成致密的网络。PRP-水凝胶显著促进子宫内膜细胞增殖，表现出强烈的促血管生成作用，并通过抑制 TGF-β1-SMAD2/3 通路在体外下调胶原蛋白沉积基因的表达。在大鼠宫腔粘连（IUA）模型的体内实验中，PRP-水凝胶显著促进了子宫内膜再生并恢复了子宫功能。此外，用 PRP-水凝胶处理的大鼠胚胎数量、窝仔数和出生率增加，与正常大鼠相似。总的来说，这种可注射的互穿双网络水凝胶能够定位激活 PRP，为子宫内膜修复提供了一种新的治疗方法。
