Magnetically responsive micro-clustered calcium phosphate-reinforced cell-laden microbead sodium alginate hydrogel for accelerated osteogenic tissue regeneration.

The rising prevalence of bone injuries has increased the demand for minimally invasive treatments. Microbead hydrogels, renowned for cell encapsulation, provide a versatile substrate for bone tissue regeneration. They deliver bioactive agents, support cell growth, and promote osteogenesis, aiding bone repair and regeneration. In this study, we synthesized superparamagnetic iron oxide nanoparticles (Sp) coated with a calcium phosphate layer (m-Sp), achieving a distinctive flower-like micro-cluster morphology. Subsequently, sodium alginate (SA) microbead hydrogels containing m-Sp (McSa@m-Sp) were fabricated using a dropping gelation strategy. McSa@m-Sp is magnetically targetable, enhance cross-linking, control degradation rates, and provide strong antibacterial activity. Encapsulation studies with MC3T3-E1 cells revealed enhanced viability and proliferation. These studies also indicated significantly elevated alkaline phosphatase (ALP) activity and mineralization in MC3T3-E1 cells, as confirmed by Alizarin Red S (ARS) and Von Kossa staining, along with increased collagen production within the McSa@m-Sp microbead hydrogels. Immunocytochemistry (ICC) and gene expression studies supported the osteoinductive potential of McSa@m-Sp, showing increased expression of osteogenic markers including RUNX-2, collagen-I, osteopontin, and osteocalcin. Thus, McSa@m-Sp microbead hydrogels offer a promising strategy for multifunctional scaffolds in bone tissue engineering.

Cu-MSNs and ZnO nanoparticles incorporated poly(ethylene glycol) diacrylate/sodium alginate double network hydrogel for simultaneous enhancement of osteogenic differentiation.

In this study, a double network (DN) hydrogel was synthesized using poly(ethylene glycol) diacrylate (PEGDA) and sodium alginate (SA), incorporating copper-doped mesoporous silica nanospheres (Cu-MSNs) and zinc oxide nanoparticles (ZnO NPs). The blending of PEGDA and SA (PS) facilitates the double network and improves the less porous microstructure of pure PEGDA hydrogel. Furthermore, the incorporation of ZnO NPs and Cu-MSNs into the hydrogel network (PS@ZnO/Cu-MSNs) improved the mechanical properties of the hydrogel (Compressive strength = ⁓153 kPa and Young's modulus = ⁓ 1.66 kPa) when compared to PS hydrogel alone (Compressive strength = ⁓ 103 kPa and Young's modulus = ⁓ 0.95 kPa). In addition, the PS@ZnO/Cu-MSNs composite hydrogel showed antibacterial activities against Staphylococcus aureus and Escherichia coli. Importantly, the PS@ZnO/Cu-MSNs hydrogel demonstrated excellent biocompatibility, enhanced MC3T3-E1 cell adhesion, proliferation, and significant early-stage osteoblastic differentiation, as evidenced by increased alkaline phosphatase (ALP), and improved calcium mineralization, as evidenced by increased alizarin red staining (ARS) activities. These findings point to the possible use of the PS@ZnO/Cu-MSNs composite hydrogel in bone tissue regeneration.

Construction of a PEGDA/chitosan hydrogel incorporating mineralized copper-doped mesoporous silica nanospheres for accelerated bone regeneration.

Hydrogels, integrating diverse biocompatible materials, have emerged as promising candidates for bone repair applications. This study presents a double network hydrogel designed for bone tissue engineering, combining poly(ethylene glycol) diacrylate (PEGDA) and chitosan (CS) crosslinked through UV polymerization and ionic crosslinking. Concurrently, copper-doped mesoporous silica nanospheres (Cu-MSNs) were synthesized using a one-pot method. Cu-MSNs underwent additional modification through in-situ biomineralization, resulting in the formation of an apatite layer. Polydopamine was employed to facilitate the deposition of Calcium (Ca) and Phosphate (P) ions on the surface of Cu-MSNs (Cu-MSNs/PDA@CaP). Composite hydrogels were created by integrating varied concentrations of Cu-MSNs/PDA@CaP (25, 50, 100, 150, 200 µg/mL). Characterization unveiled distinctive interconnected porous structures within the composite hydrogel, showcasing a notable 169.6 % enhancement in compressive stress (elevating from 89.01 to 240.19 kPa) compared to pure PEGDA. In vitro biocompatibility experiments illustrated that the composite hydrogel maintained elevated cell viability (up to 106.6 %) and facilitated rapid cell proliferation over 7 days. The hydrogel demonstrated a substantial 57.58 % rise in ALP expression and a surprising 235.27 % increase in ARS staining. Moreover, it significantly enhanced the expression of crucial osteogenic genes, such as run-related transcription factors 2 (RUNX2), collagen 1a1 (Col1a1), and secreted phosphoprotein 1 (Spp1), establishing it as a promising scaffold for bone regeneration. This study shows how Cu-MSNs/PDA@CaP were successfully integrated into a double network hydrogel, resulting in a composite material with good biological responses. Due to its improved characteristics, this composite hydrogel holds the potential for advancing bone regeneration procedures.