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Microsphere embedded hydrogel construct - binary delivery of alendronate and BMP-2 for superior bone regeneration
Sayanti Datta1, Arun Prabhu Rameshbabu, Kamakshi Bankoti
1Biomaterials and Tissue Engineering Laboratory, School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur - 721302, India. sdhara@smst.iitkgp.ac.in.
Journal of Materials Chemistry. B
|August 16, 2021
Summary
This study developed a novel hydrogel construct for bone regeneration, combining decellularized bone extracellular matrix with microspheres for controlled release of bone morphogenic protein-2 and alendronate, showing enhanced bone healing in rabbits.
Area of Science:
- Biomaterials Science
- Tissue Engineering
- Regenerative Medicine
Background:
- Bone extracellular matrix (ECM) is a natural scaffold for bone regeneration, but native ECM hydrogels have limitations like poor mechanical strength and reduced growth factor content.
- Decellularized bone ECM (dECM) offers a promising biomaterial, but requires modification for enhanced functionality and controlled delivery of therapeutic agents.
Purpose of the Study:
- To develop a multifunctional hydrogel construct for enhanced bone regeneration by combining dECM with microspheres for dual drug delivery.
- To evaluate the efficacy of this construct in delivering bone morphogenic protein-2 (BMP-2) and alendronate (ALN) for stimulating bone repair in a rabbit tibial defect model.
Main Methods:
- A hydrogel construct (BOC) was fabricated using decellularized bone ECM and oleoyl chitosan, embedding gelatin microspheres (GMs) for alendronate (ALN) delivery.
- The construct facilitated sustained release of ALN and BMP-2, and its biocompatibility was assessed using human amniotic membrane-derived stem cells (HAMSCs).
- Osteogenic differentiation, mineralization, vascularization, and bone regeneration in a rabbit tibial defect model were evaluated using various assays and imaging techniques.
Main Results:
- The BOC construct demonstrated sustained release of both ALN and BMP-2, with excellent biocompatibility and proliferation of HAMSCs.
- Significant upregulation of osteogenic genes, enhanced matrix deposition, and improved neo-vascularization were observed.
- Histological and CT analyses confirmed accelerated bone regeneration in the BOC/ALN/BMP treated group compared to controls.
Conclusions:
- The developed multifunctional hydrogel construct serves as an osteoconductive and osteoinductive platform for bone tissue engineering.
- Controlled dual delivery of ALN and BMP-2 via this hydrogel significantly enhances bone regeneration in a preclinical model.
- This approach holds potential for treating critical-sized bone defects.
