Injectable Hydrogel with NIR Light-Responsive, Dual-Mode PTH Release for Osteoregeneration in Osteoporosis,Advanced Functional Materials

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Injectable Hydrogel with NIR Light-Responsive, Dual-Mode PTH Release for Osteoregeneration in Osteoporosis
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2021-08-26 , DOI: 10.1002/adfm.202105383
Lijun Kuang ₁ , Jinghuan Huang ₂ , Yutong Liu ₁ , Xiaolin Li ₂ , Yuan Yuan ₁ , Changsheng Liu ₁

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Effective treatments to overcome osteoblast/osteoclast imbalance are the key to achieving desirable bone regeneration for osteoporosis patients. When used for local bone repair, parathyroid hormone (PTH) often leads to either excessive osteoclasts under continuous exposure or insufficient osteoclasts with pulsatile release of PTH. Herein, an injectable multifunctional in situ-generated calcium phosphate nanoparticle (ICPN)-coordinated poly(dimethylaminoethyl methacrylate-co-2-hydroxyethyl methacrylate) (DHCP) hydrogel loaded with PTH for near-infrared (NIR)-stimulated release is developed to achieve bone regeneration in an ovariectomized (OVX) model. Photothermal-responsive poly(N-acryloyl glycinamide-co-acrylamide) PNAm-indocyanine green ICG-PTH microspheres (PIP MSs) endow a dual-mode release system with a sustained release at low concentrations, a pulse release of PTH, and in situ pore formation properties. The PIP MS-encapsulated DHCP hydrogel (DHCP-10PIP/d) is injected into the bone defects of OVX rats. Under NIR irradiation, the localized photothermal effects trigger on-demand PTH release and in situ micropores formation through the gel–sol transition of PIP MSs, and the repeated treatment is harmless to the bioactivity of PTH. This platform can enhance osteoblast and osteoclast activity at the same time both in vitro and in vivo and repair the cranial defects of OVX rats successfully. Overall, this work provides a promising strategy for PTH delivery to repair osteoporotic bone defects.

中文翻译：

具有近红外光响应、双模式 PTH 释放的可注射水凝胶用于骨质疏松症的骨再生

克服成骨细胞/破骨细胞失衡的有效治疗是骨质疏松症患者实现理想骨再生的关键。当用于局部骨修复时，甲状旁腺激素 (PTH) 通常会导致持续暴露下的破骨细胞过多或 PTH 脉冲释放的破骨细胞不足。在此，开发了一种可注射的多功能原位生成磷酸钙纳米颗粒 (ICPN) 配位的聚甲基丙烯酸二甲氨基乙酯-co-2-羟乙基甲基丙烯酸酯 (DHCP) 水凝胶，其负载 PTH 用于近红外 (NIR) 刺激释放，以实现卵巢切除（OVX）模型中的骨再生。光热响应聚（N-丙烯酰甘氨酰胺-共-丙烯酰胺）PNAm-吲哚菁绿ICG-PTH微球（PIP MSs）赋予双模式释放系统，在低浓度下持续释放，PTH 的脉冲释放和原位成孔特性。将 PIP MS 封装的 DHCP 水凝胶 (DHCP-10PIP/d) 注射到 OVX 大鼠的骨缺损中。在 NIR 照射下，局部光热效应通过 PIP MS 的凝胶-溶胶转变触发 PTH 按需释放和原位微孔形成，重复处理对 PTH 的生物活性无害。该平台可在体外和体内同时增强成骨细胞和破骨细胞的活性，成功修复OVX大鼠的颅骨缺损。总体而言，这项工作为 PTH 递送修复骨质疏松性骨缺损提供了一种有前景的策略。局部光热效应通过 PIP MS 的凝胶-溶胶转变触发 PTH 按需释放和原位微孔形成，重复处理对 PTH 的生物活性无害。该平台可在体外和体内同时增强成骨细胞和破骨细胞的活性，成功修复OVX大鼠的颅骨缺损。总体而言，这项工作为 PTH 递送修复骨质疏松性骨缺损提供了一种有前景的策略。局部光热效应通过 PIP MS 的凝胶-溶胶转变触发 PTH 按需释放和原位微孔形成，重复处理对 PTH 的生物活性无害。该平台可在体外和体内同时增强成骨细胞和破骨细胞的活性，成功修复OVX大鼠的颅骨缺损。总体而言，这项工作为 PTH 递送修复骨质疏松性骨缺损提供了一种有前景的策略。

更新日期：2021-08-26

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