Strontium-loaded multifunctional gelatin methacryloyl hydrogels for type-H vascularized bone regeneration under osteoporotic conditions

Osteoporosis (OP) is a clinically prevalent bone disease, under which excessive activation of osteoclasts (OCs) significantly delays bone regeneration. In this context, bone regeneration necessitates not merely the facilitation of osteogenesis and the suppression of resorption, but also more stringe...

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Main Authors: Yuwei He, Fanchun Zeng, Hongyu Quan, Lanyi Liu, Jingjin Dai, Hong Jiang, Shiwu Dong
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Materials Today Bio
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Online Access:http://www.sciencedirect.com/science/article/pii/S259000642500479X
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author Yuwei He
Fanchun Zeng
Hongyu Quan
Lanyi Liu
Jingjin Dai
Hong Jiang
Shiwu Dong
author_facet Yuwei He
Fanchun Zeng
Hongyu Quan
Lanyi Liu
Jingjin Dai
Hong Jiang
Shiwu Dong
author_sort Yuwei He
collection DOAJ
description Osteoporosis (OP) is a clinically prevalent bone disease, under which excessive activation of osteoclasts (OCs) significantly delays bone regeneration. In this context, bone regeneration necessitates not merely the facilitation of osteogenesis and the suppression of resorption, but also more stringent requirements pertaining to vascularization, particularly type-H blood vessels. Recently, strontium (Sr) has emerged as a ''dual-action bone agent'', enhancing bone formation while suppressing bone resorption, yet still receives inadequate attention. Given that PDGF-BB secreted by osteoclast progenitors (pOCs) could induce type-H-related vascularization during coupling with osteogenesis, the regulatory effect of Sr2+ on osteoclastogenesis need to be further studied and utilized in vascularized bone regeneration. Here, we synthesized Sr-substituted layered double hydroxide (Sr-LDH) by partially substituting divalent metal ions in LDH with Sr2+, and encapsulated the surface-modified Sr-LDH into QK peptide-incorporated gelatin methacryloyl (GelMA) to form a composite hydrogel GelMA-QK/Sr-LDH@PDA (GLQ). This multifunctional hydrogel integrated the osteogenic and antiresorptive properties of Sr-LDH, exhibited significant bone regeneration efficacy under osteoporotic conditions. Furthermore, our study found that GLQ could stimulate bone marrow derived macrophages (BMMs) proliferation and preserve pOCs while suppress OC maturation, which further facilitated the expression of PDGF-BB and promoted type-H vessels development in the bone defect area. Taken together, the multifunctional composite hydrogel holds significant clinical implications for future treatment of osteoporotic bone defects.
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spelling doaj-art-ff5b2cedb40b497083a06b4ebe93216a2025-08-20T03:19:53ZengElsevierMaterials Today Bio2590-00642025-06-013210190910.1016/j.mtbio.2025.101909Strontium-loaded multifunctional gelatin methacryloyl hydrogels for type-H vascularized bone regeneration under osteoporotic conditionsYuwei He0Fanchun Zeng1Hongyu Quan2Lanyi Liu3Jingjin Dai4Hong Jiang5Shiwu Dong6Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing, 400038, ChinaDepartment of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing, 400038, China; Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Medical School, Shenzhen University, Shenzhen, 518060, ChinaDepartment of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing, 400038, ChinaDepartment of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing, 400038, ChinaDepartment of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing, 400038, ChinaDepartment of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing, 400038, China; Corresponding author.Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing, 400038, China; State Key Laboratory of Trauma and Chemical Poisoning, Third Military Medical University, Chongqing, 400038, China; Corresponding author. Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing, 400038, China.Osteoporosis (OP) is a clinically prevalent bone disease, under which excessive activation of osteoclasts (OCs) significantly delays bone regeneration. In this context, bone regeneration necessitates not merely the facilitation of osteogenesis and the suppression of resorption, but also more stringent requirements pertaining to vascularization, particularly type-H blood vessels. Recently, strontium (Sr) has emerged as a ''dual-action bone agent'', enhancing bone formation while suppressing bone resorption, yet still receives inadequate attention. Given that PDGF-BB secreted by osteoclast progenitors (pOCs) could induce type-H-related vascularization during coupling with osteogenesis, the regulatory effect of Sr2+ on osteoclastogenesis need to be further studied and utilized in vascularized bone regeneration. Here, we synthesized Sr-substituted layered double hydroxide (Sr-LDH) by partially substituting divalent metal ions in LDH with Sr2+, and encapsulated the surface-modified Sr-LDH into QK peptide-incorporated gelatin methacryloyl (GelMA) to form a composite hydrogel GelMA-QK/Sr-LDH@PDA (GLQ). This multifunctional hydrogel integrated the osteogenic and antiresorptive properties of Sr-LDH, exhibited significant bone regeneration efficacy under osteoporotic conditions. Furthermore, our study found that GLQ could stimulate bone marrow derived macrophages (BMMs) proliferation and preserve pOCs while suppress OC maturation, which further facilitated the expression of PDGF-BB and promoted type-H vessels development in the bone defect area. Taken together, the multifunctional composite hydrogel holds significant clinical implications for future treatment of osteoporotic bone defects.http://www.sciencedirect.com/science/article/pii/S259000642500479XOsteoporosisBone regenerationType-H blood vesselsStrontiumMultifunctional hydrogel
spellingShingle Yuwei He
Fanchun Zeng
Hongyu Quan
Lanyi Liu
Jingjin Dai
Hong Jiang
Shiwu Dong
Strontium-loaded multifunctional gelatin methacryloyl hydrogels for type-H vascularized bone regeneration under osteoporotic conditions
Materials Today Bio
Osteoporosis
Bone regeneration
Type-H blood vessels
Strontium
Multifunctional hydrogel
title Strontium-loaded multifunctional gelatin methacryloyl hydrogels for type-H vascularized bone regeneration under osteoporotic conditions
title_full Strontium-loaded multifunctional gelatin methacryloyl hydrogels for type-H vascularized bone regeneration under osteoporotic conditions
title_fullStr Strontium-loaded multifunctional gelatin methacryloyl hydrogels for type-H vascularized bone regeneration under osteoporotic conditions
title_full_unstemmed Strontium-loaded multifunctional gelatin methacryloyl hydrogels for type-H vascularized bone regeneration under osteoporotic conditions
title_short Strontium-loaded multifunctional gelatin methacryloyl hydrogels for type-H vascularized bone regeneration under osteoporotic conditions
title_sort strontium loaded multifunctional gelatin methacryloyl hydrogels for type h vascularized bone regeneration under osteoporotic conditions
topic Osteoporosis
Bone regeneration
Type-H blood vessels
Strontium
Multifunctional hydrogel
url http://www.sciencedirect.com/science/article/pii/S259000642500479X
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