Injectable in situ gelling methylcellulose-based hydrogels for bone tissue regeneration

• Published in: Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2024-05, Vol.12 (18), p.4427-4440
• Main Authors: Bonetti, Lorenzo, Borsacchi, Silvia, Soriente, Alessandra, Boccali, Alberto, Calucci, Lucia, Raucci, Maria Grazia, Altomare, Lina
• Format: Article
• Language: English
• Subjects: Adhesion; Biomedical materials; Biomimetics; Body fluids; Body temperature; Bone biomaterials; Bone growth; Bones; Calcium phosphates; Cell adhesion; Cell adhesion & migration; Cell differentiation; Composite materials; Crystal defects; Differentiation (biology); Graphene; Hydrogels; Hydroxyapatite; In vitro methods and tests; Injectability; Mechanical loading; Mechanical properties; Methylcellulose; Mineralization; NMR; Nuclear magnetic resonance; Regeneration; Regeneration (physiology); Room temperature; Substitute bone; Tissue engineering; Transition temperature; Transition temperatures; X-ray diffraction
• ISSN: 2050-750X; 2050-7518
• DOI: 10.1039/d3tb02414h

Injectable bone substitutes (IBSs) represent a compelling choice for bone tissue regeneration, as they can be exploited to optimally fill complex bone defects in a minimally invasive manner. In this context, gelling methylcellulose (MC) hydrogels may be engineered to be free-flowing injectable solutions at room temperature and gels upon exposure to body temperature. Moreover, incorporating a suitable inorganic phase can further enhance the mechanical properties of MC hydrogels and promote mineralization, thus assisting early cell adhesion to the hydrogel and effectively guiding bone tissue regeneration. In this work, thermo-responsive IBSs were designed selecting MC as the organic matrix and calcium phosphate (CaP) or CaP modified with graphene oxide (CaPGO) as the inorganic component. The resulting biocomposites displayed a transition temperature around body temperature, preserved injectability even after loading with the inorganic components, and exhibited adequate retention on an calf femoral bone defect model. The addition of CaP and CaPGO promoted the mineralization process already 14 days after immersion in simulated body fluid. Interestingly, combined X-ray diffraction and solid state nuclear magnetic resonance characterizations revealed that the formed biomimetic phase was constituted by crystalline hydroxyapatite and amorphous calcium phosphate. biological characterization revealed the beneficial impact of CaP and CaPGO, indicating their potential in promoting cell adhesion, proliferation and osteogenic differentiation. Remarkably, the addition of GO, which is very attractive for its bioactive properties, did not negatively affect the injectability of the hydrogel nor the mineralization process, but had a positive impact on cell growth and osteogenic differentiation on both pre-differentiated and undifferentiated cells. Overall, the proposed formulations represent potential candidates for use as IBSs for application in bone regeneration both under physiological and pathological conditions.