Combined Molybdenum Gelatine Methacrylate Injectable Nano-Hydrogel Effective Against Diabetic Bone Regeneration.

Int J Nanomedicine

Department of Orthopedics, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, People's Republic of China.

Published: October 2023

AI Article Synopsis

  • Bone defects caused by diabetes are difficult to treat due to fluctuating glucose levels, which produce harmful reactive oxygen species (ROS) that disrupt bone healing.
  • Researchers developed a new hydrogel made from gelatin methacrylate (GelMA) and molybdenum (Mo)-based polyoxometalate nanoclusters (POM) to help manage ROS and support bone cell growth and differentiation.
  • The GelMA/POM hydrogel showed promising results in lab experiments, effectively reducing ROS and promoting bone regeneration in diabetic mice, potentially opening new avenues for treatment of bone defects in diabetes.

Article Abstract

Introduction: Bone defects in diabetes mellitus (DM) remain a major challenge for clinical treatment. Fluctuating glucose levels in DM patients lead to excessive production of reactive oxygen species (ROS), which disrupt bone repair homeostasis. Bone filler materials have been widely used in the clinical treatment of DM-related bone defects, but overall they lack efficacy in improving the bone microenvironment and inducing osteogenesis. We utilized a gelatine methacrylate (GelMA) hydrogel with excellent biological properties in combination with molybdenum (Mo)-based polyoxometalate nanoclusters (POM) to scavenge ROS and promote osteoblast proliferation and osteogenic differentiation through the slow-release effect of POM, providing a feasible strategy for the application of biologically useful bone fillers in bone regeneration.

Methods: We synthesized an injectable hydrogel by gelatine methacrylate (GelMA) and POM. The antioxidant capacity and biological properties of the synthesized GelMA/POM hydrogel were tested.

Results: In vitro, studies showed that hydrogels can inhibit excessive reactive oxygen species (ROS) and reduce oxidative stress in cells through the beneficial effects of pH-sensitive POM. Osteogenic differentiation assays showed that GelMA/POM had good osteogenic properties with upregulated expression of osteogenic genes (BMP2, RUNX2, Osterix, ALP). Furthermore, RNA-sequencing revealed that activation of the PI3K/Akt signalling pathway in MC3T3-E1 cells with GelMA/POM may be a potential mechanism to promote osteogenesis. In an in vivo study, radiological and histological analyses showed enhanced bone regeneration in diabetic mice, after the application of GelMA/POM.

Conclusion: In summary, GelMA/POM hydrogels can enhance bone regeneration by directly scavenging ROS and activating the PI3K/Akt signalling pathway.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10596232PMC
http://dx.doi.org/10.2147/IJN.S428429DOI Listing

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