Dual-controlled release of PTH(1–34) via microsphere-hydrogel scaffold promotes early bone regeneration in osteoporosis

IF 6.7 3区材料科学 Q2 CHEMISTRY, PHYSICAL

Colloid and Interface Science Communications Pub Date : 2026-01-01 Epub Date: 2025-12-02 DOI:10.1016/j.colcom.2025.100864

Siuman Leung , Xiaohong Li , Xiaoqiong Huang , Ruogu Xu , Hio Kuan Wu , Jiali Deng , Feilong Deng , Shuang-Zhuang Guo , Yun Liu

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引用次数: 0

Abstract

This study developed a three-dimensional (3D)-printed dual-controlled release scaffold for localized, sustained parathyroid hormone 1–34 (PTH 1–34) delivery to overcome systemic limitations (inadequate spatiotemporal control, poor anatomical matching) and enhance early bone regeneration in osteoporotic defects. PTH(1–34)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres (68.2 % efficiency) were incorporated into chitosan (CS) /short rod-shaped nano-hydroxyapatite (nHA) hydrogel ink and 3D-printed (300 μm nozzle). In vitro, scaffolds exhibited sustained biphasic release (19.4 ± 2.1 % initial burst within 24 h and 71.8 ± 1.7 % cumulative release over 30 days), significantly promoting MC3T3-E1 proliferation, alkaline phosphatase (ALP) activity (3.08-fold vs control, day 14; p < 0.01), and runt-related transcription factor 2 (Runx2) expression (8.13-fold; p < 0.001). In vivo (Ovariectomy rats, 5-mm calvarial defects; n = 5/group), Micro-computed tomography (micro-CT) at 4 weeks showed 2.22-fold higher trabecular bone volume fraction (BV/TV) (p < 0.001) with 73 % greater trabecular thickness (p < 0.001), confirmed histologically by accelerated mineralization/osteoblast activation. The PTH(1–34)@PLGA/CS-nHA scaffold integrates spatiotemporal drug delivery and biomimetic architecture, offering a promising strategy for early-phase bone regeneration in osteoporosis.

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微球-水凝胶支架促PTH（1-34）双控释促进骨质疏松早期骨再生

本研究开发了一种三维（3D）打印的双控释放支架，用于局部、持续递送甲状旁腺激素1-34 (PTH 1-34)，以克服全身局限性（时空控制不足、解剖匹配差），促进骨质疏松性缺陷的早期骨再生。将负载PTH（1-34）的聚乳酸-羟基乙酸（PLGA）微球（效率为68.2%）加入壳聚糖(CS) /短棒状纳米羟基磷灰石（nHA）水凝胶墨水中，3d打印（300 μm喷嘴）。体外，支架表现出持续的双相释放（24 h内初始释放19.4±2.1%，30 d内累积释放71.8±1.7%），显著促进MC3T3-E1增殖、碱性磷酸酶（ALP）活性（第14天比对照3.08倍；p < 0.01）和矮子相关转录因子2 （Runx2）表达（8.13倍；p < 0.001）。在体内（卵巢切除大鼠，5mm颅骨缺损，n = 5/组），微计算机断层扫描（微ct）显示，4周时小梁骨体积分数（BV/TV）增加2.22倍（p < 0.001），小梁厚度增加73% (p < 0.001)，组织学上证实矿化/成骨细胞激活加速。PTH(1-34)@PLGA/CS-nHA支架结合了时空给药和仿生结构，为骨质疏松症早期骨再生提供了一种有前景的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Colloid and Interface Science Communications Materials Science-Materials Chemistry

CiteScore

9.40

自引率

6.70%

发文量

125

审稿时长

43 days

期刊介绍： Colloid and Interface Science Communications provides a forum for the highest visibility and rapid publication of short initial reports on new fundamental concepts, research findings, and topical applications at the forefront of the increasingly interdisciplinary area of colloid and interface science.