Characterizing the release profile for materials-directed local delivery of bioactive molecules and its effect on bone regeneration is an important step to improve our understanding of, and ability to optimize, the bone healing response. This study examined the local delivery of parathyroid hormone (PTH) using a thiol-ene hydrogel embedded in a porous poly(propylene fumarate) (PPF) scaffold for bone regeneration applications. The aim of this study was to characterize the degradation-controlled in vitro release kinetics of PTH from the thiol-ene hydrogels, in vivo hydrogel degradation in a subcutaneous implant model, and bone healing in a rat critical size bone defect. Tethering PTH to the hydrogel matrix eliminated the early timepoint burst release that was observed in previous in vitro work where PTH was free to diffuse out of the matrix. Only 8% of the tethered PTH was released from the hydrogel during the first 2 weeks, but by day 21, 80% of the PTH was released, and complete release was achieved by day 28. In vivo implantation revealed that complete degradation of the hydrogel alone occurred by day 21; however, when incorporated in a three-dimensional printed osteoconductive PPF scaffold, the hydrogel persisted for >56 days. Treatment of bone defects with the composite thiol-ene hydrogel–PPF scaffold, delivering either 3 or 10 μg of tethered PTH 1-84, was found to increase bridging of critical size bone defects, whereas treatment with 30 μg of tethered PTH resulted in less bone ingrowth into the defect area. Continued development of this biomaterial delivery system for PTH could lead to improved therapies for treatment of nonunion fractures and critical size bone defects.

中文翻译：

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释放动力学对局部提供的甲状旁腺激素在骨再生应用中功效的影响

表征材料导向的生物活性分子局部递送的释放曲线及其对骨再生的影响是提高我们对骨愈合反应的理解和优化能力的重要一步。本研究使用嵌入多孔聚富马酸丙二醇酯 (PPF) 支架中的硫醇烯水凝胶来检测甲状旁腺激素 (PTH) 的局部递送，用于骨再生应用。本研究的目的是描述硫醇-烯水凝胶中 PTH的降解控制体外释放动力学、皮下植入模型中的体内水凝胶降解以及大鼠临界尺寸骨缺损中的骨愈合。将 PTH 束缚在水凝胶基质上消除了之前观察到的早期时间点爆发释放PTH 可以自由扩散出基质的体外工作。在前 2 周内，只有 8% 的束缚 PTH 从水凝胶中释放出来，但到第 21 天，释放了 80% 的 PTH，到第 28 天完全释放。植入显示，仅水凝胶在第 21 天就发生了完全降解；然而，当结合到一个 3D 打印的骨传导 PPF 支架中时，水凝胶可以持续超过 56 天。发现使用复合硫醇-烯水凝胶-PPF 支架治疗骨缺损，输送 3 或 10 μg 栓系 PTH 1-84，可增加临界尺寸骨缺损的桥接，而使用 30 μg 栓系 PTH 治疗导致更少骨长入缺损区。这种用于 PTH 的生物材料输送系统的持续开发可能会导致改进治疗骨不连骨折和临界尺寸骨缺损的疗法。