What question did this study set out to answer?

The study aims to develop a multifunctional hydrogel to enhance osteoporotic osseointegration using ion/drug delivery systems.

April 16, 2026Open Access

Multifunctional ions/drugs co-delivering nanocomposite hydrogel orchestrates neuro-osteogenic microenvironment for boosting osteoporotic osseointegration

SJShengyang JinChinese Academy of Medical Sciences & Peking Union Medical College IUIsmat UllahFederal Urdu University ZCZ ChenSuzhou University of Science and Technology

Key Points

The study aims to develop a multifunctional hydrogel to enhance osteoporotic osseointegration using ion/drug delivery systems.
Encapsulated parathyroid hormone in Sr2+/Zn2+ co-doped mesoporous silica nanoparticles.
Incorporated nanoparticles into gelatin methacrylate with calcitonin gene related peptide.
Characterized the hydrogels for injectability, degradation, and ion/drug release properties.
Assessed biological effects on sensory neurons and bone marrow stem cells.
Evaluated in vivo effects in osteoporotic rat models.
Hydrogels displayed excellent injectability and sustained release of therapeutic agents.
Enhanced expression of neurotrophic factors (NGF and BDNF) in bone marrow stem cells.
Increased axonal outgrowth and neuron activation observed.
In vivo results confirmed improved peri-implant nerve growth and bone formation in rat models.

Abstract

With population aging, the incidence of osteoporosis continuously elevates worldwide, resulting in increased fracture risks and clinical demand for orthopedic fixation. However, under osteoporotic conditions, the stability and longevity of implants are severely compromised by the pathological microenvironment, thus developing effective therapeutic interventions to achieve successful osteoporotic osseointegration remains a critical challenge in the regenerative medicine field. Herein, the parathyroid hormone (PTH) is encapsulated in Sr2+/Zn2+ co-doped mesoporous silica nanoparticles (SrZn-MSNs) to synthesize P@SrZn-MSNs, which are then incorporated into gelatin methacrylate (GelMA) containing calcitonin gene related peptide (CGRP) for realizing bioactive ions/drugs co-delivery. The obtained Gel/P@SrZn-MSNs/G nanocomposite hydrogels are characterized by excellent injectability and photosensitivity, 3D interconnected porous architecture, durable degradation and concurrent releasing of Si/Sr/Zn ions, CGRP and PTH controlled within proper doses. These favorable properties endow Gel/P@SrZn-MSNs/G with superior biological multifunctionality that not only promotes functionality of DRG sensory neurons and BMSCs directly, but also manipulates mutually beneficial interactions of DRG/BMSCs to further stimulate neurogenesis/osteogenesis. Specifically, Gel/P@SrZn-MSNs/G mainly increases NGF and BDNF expressions in BMSCs to stimulate axonal outgrowth and activation of DRG neurons, and in turn, the up-regulation of Sema3A in DRG neurons could be responsible for the neuro-inductive osteogenesis. Consistently, the in vivo outcomes further validate the potent and timely peri-implant innervation and bone formation induced by Gel/P@SrZn-MSNs/G when applied to femoral condyle defects of OVX rats. These results highlight the efficient ions/drugs co-delivery system renders Gel/P@SrZn-MSNs/G exerting synergy bioeffects to orchestrate desired neuro-osteogenic niches for boosting osteoporotic osseointegration, thus may inspiring new therapeutic strategies for osteoporotic bone healing.

KI fragen

Bookmark

View Full Paper