Enzyme-delivery Metal-organic Framework Composite Coatings for Restoration of Hyperglycemia-damaged Osteoblast Differentiation

There is a significant clinical need to develop effective treatments for bone defects in patients with diabetes mellitus (DM), as they are at higher risk of fractures and impaired healing. Guided bone tissue engineering using biocompatible and biodegradable polymers is a promising approach. However, current diabetic bone regenerative therapies often fail due to the accumulation of advanced glycation products, which can affect the integration of traditional tissue engineering scaffolds with native bone. Therefore, novel approaches are needed to improve the efficacy of diabetic bone regeneration. This study presents a proof-of-concept development of a multifunctional polymer composite coating tailored towards restoring diabetes-related damage in osteoblast differentiation. Our composite system involves 3D-printed poly(caprolactone fumarate) (PCLF) and poly(caprolactone) (PCL) blend scaffolds coated with multifunctional chitosan methacrylate (chiMA). The chiMA coating is embedded with a sustained-release formulation of glucose oxidase (GOx) from MIL-127 metal-organic frameworks making the coating a stimuli-responsive biomolecule delivery system. The multifunctional coating is designed for the sustained release of GOx and sodium pyruvate for in vitro glucose modulation and oxidative stress reduction, respectively. We propose that sustained release of GOx from MIL-127 embedded chiMA coatings can modulate the high glucose (HG) cellular milieu towards normal glucose (NG), enhancing osteoblast (OB) differentiation via downstream effects. Our results show successful synthesis of MIL-127, encapsulation of GOx, and fabrication of composite coating on the PCLF/PCL scaffolds with effective enzyme activity measured as a function of lowering glucose concentration in HG media for 144 h to normal levels. In vitro evaluation of OB viability, attachment, proliferation, and differentiation showed an overall decrease in cellular activity in HG conditions, which was restored through the glucose-modulating functionality of the GOx-releasing MIL-127 coatings. Our results also presented preliminary evidence of a statistical correlation between DM-related gene markers and osteogenic markers in vitro that requires further exploration. Although this proof-of-concept study holds promise for advancing precision biomaterials development for diabetic tissue engineering and meeting the unmet clinical need for effective treatments and warrants future in vivo evaluation of the composite coating and molecular biology understanding of correlations between DM and osteogenic markers.