Thiol-ene Hydrogels for Local Delivery of PTH for Bone Regeneration in Critical Size defects.

Thiol-ene Hydrogels for Local Delivery of PTH for Bone Regeneration in Critical Size defects.
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用于局部递送 PTH 的硫醇烯水凝胶,用于临界尺寸缺损的骨再生。

DOI:
10.1002/jor.24502
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发表时间:
2020
期刊:
Journal of orthopaedic research : official publication of the Orthopaedic Research Society
影响因子:
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通讯作者:
Donahue,SethW
Donahue,SethW
中科院分区:
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文献类型:
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作者:
Wojda,SamanthaJ;Marozas,IanA;Anseth,KristiS;Yaszemski,MichaelJ;Donahue,SethW

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同种异体移植物和市售骨移植替代物都无法提供与自体移植物相同的骨愈合质量。将甲状旁腺激素 (PTH) 等生物活性分子纳入骨移植替代材料中,即使不是更好的移植治疗选择,也可以提供类似的治疗选择。这项工作的目标是开发一种生物材料系统,用于将 PTH 局部输送到大骨缺损处,以促进骨再生。 PTH 以多种浓度装载在硫醇烯水凝胶中,并在骨传导性聚富马酸丙烯酯 (PPF) 支架内和周围聚合。 PTH 从水凝胶中释放长达 21 天后被证明具有生物活性。 80% 的 PTH 在第 3 天释放,其余 20% 在第 14 天释放。对用水凝胶/PPF 和 0、1、3、10 或 30μg PTH 治疗的大鼠临界尺寸股骨缺损的骨愈合进行量化。尽管在任何一个治疗组的所有样本中均未观察到完全的骨愈合,但 10μg PTH 组中的所有样本均由骨或包含肥大软骨细胞和软骨内骨化的骨和软骨的组合完全桥接。结果测量表明,与空骨缺损和仅用水凝胶/PPF(即无 PTH)治疗的缺损相比,10μg 治疗组中骨和软骨组织的组合改善了缺损桥接。鉴于水凝胶的可定制性,未来的研究将调查长期逐渐释放 PTH 对骨愈合的影响。 © 2019 骨科研究会。由 Wiley periodicals, Inc. 出版。J Orthop Res 38:536–544, 2020
Neither allograft nor commercially available bone graft substitutes provide the same quality of bone healing as autograft. Incorporation of bioactive molecules like parathyroid hormone (PTH) within bone graft substitute materials may provide similar, if not better treatment options to grafting. The goal of this work was to develop a biomaterial system for the local delivery of PTH to large bone defects for promoting bone regeneration. PTH was loaded in a thiol‐ene hydrogel at several concentrations and polymerized in and around an osteoconductive poly(propylene fumarate) (PPF) scaffold. PTH was shown to be bioactive when released from the hydrogel for up to 21 days. Eighty percent of the PTH was released by day 3 with the remaining 20% released by day 14. Bone healing was quantified in rat critical size femoral defects that were treated with hydrogel/PPF and 0, 1, 3, 10, or 30 µg of PTH. Although complete osseous healing was not observed in all samples in any one treatment group, all samples in the 10 µg PTH group were bridged fully by bone or a combination of bone and cartilage containing hypertrophic chondrocytes and endochondral ossification. Outcome measures indicated improved defect bridging by a combination of bony and cartilaginous tissue in the 10 μg treatment group compared with empty bone defects and defects treated with only hydrogel/PPF (i.e., without PTH). Given the tailorability of the hydrogel, future studies will investigate the effects of prolonged gradual PTH release on bone healing. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:536–544, 2020