Effects of the multiscale porosity of decellularized platelet-rich fibrin-loaded zinc-doped magnesium phosphate scaffolds in bone regeneration.

In recent years, metallic ion-doped magnesium phosphate (MgP)-based degradable bioceramics have emerged as alternative bone substitute materials owing to their excellent biocompatibility, bone-forming ability, bioactivity, and controlled degradability. Conversely, incorporating a biomolecule such as decellularized platelet-rich fibrin (d-PRF) on scaffolds has certain advantages for bone tissue regeneration, particularly in enhanced osteogenesis and angiogenesis. The present study focuses on the impact of d-PRF-loaded multiscale porous zinc-doped magnesium phosphate (Zn-MgP) scaffolds on biodegradability, biocompatibility, and bone regeneration. Scaffolds were fabricated through the powder-metallurgy route utilizing naphthalene as a porogen (porosity = 5-43%). With the inclusion of a higher porogen, a higher fraction of macro-porosity (>20 µm) and pore interconnectivity were observed. X-ray diffraction (XRD) studies confirmed the formation of the farringtonite phase. The developed scaffolds exhibited a minimum ultimate compressive strength (UCS) of 8.5 MPa (for 40 Naph), which lies within the range of UCS of the cancellous bone of humans (2-12 MPa). The in vitro assessment via immersion in physiological fluid yielded a higher deposition of the calcium phosphate (CaP) compound in response to increased macro-porosity and interconnectivity (40 Naph). Cytocompatibility assessed using MC3T3-E1 cells showed that the incorporation of d-PRF coupled with increased porosity resulted the highest cell attachment, proliferation, and viability. For further evaluation, the developed scaffolds were implanted in in vivo rabbit femur condylar defects. Radiography, SEM, OTC labelling, and histology analysis after 2 months of implantation revealed the better invasion of mature osteoblastic cells into the scaffolds with enhanced angiogenesis and superior and accelerated healing of bone defects in d-PRF-incorporated higher porosity scaffolds (40 Naph). Finally, it is hypothesized that the combination of d-PRF incorporation with multiscale porosity and increased interconnectivity facilitated better bone-forming ability, good biocompatibility, and controlled degradability within and around the Zn-doped MgP scaffolds.

Synergistic Improvement of Antibacterial and Osteogenic Differentiation of Thermomechanically Processed Mg-Zr-Sr-Ce Alloy: Insights into the Role of Precipitate Evolution Supported by AIMD Simulation Study.

In the present study, we have discussed the influence of forging temperature (623 K (FT623), 723 K (FT723) and 823 K (FT823)) on microstructure and texture evolution and its implication on mechanical behavior, in vitro-in vivo biocorrosion, antibacterial response, and cytocompatibility of microalloyed Mg-Zr-Sr-Ce alloy. Phase analysis, SEM, and TEM characterization confirm the presence of Mg12Ce precipitate, and its stability was further validated by performing ab initio molecular dynamic simulation study. FT723 exhibits strengthened basal texture, higher fraction of second phases, and particle-stimulated nucleation-assisted DRX grains compared to other two specimens, resulting in superior strength with comparable ductility. FT723 also exhibits superior corrosion resistance mainly due to the strengthened basal texture and lower dislocation density. All the specimens exhibit excellent antibacterial behavior with Gram-negative E. coli, Gram-positive Staphylococcus aureus, and Pseudomonas aeruginosa bacteria. 100% reduction of bacterial growth is observed within 24 h of culture of the specimens. Cytocompatibility was determined by challenging specimen extracts with the MC3T3-E1 cell lines. FT723 specimen exhibits the highest cell proliferation and alkaline phosphatase activity (ALP) because of its superior corrosion resistance. The ability of the specimens to be used in orthopedic implant application was evaluated by in vivo study in rabbit femur. Neither tissue-related infection nor the detrimental effect surrounding the implant was confirmed from histological analysis. Significant higher bone regeneration surrounding the FT723 specimen was observed in SEM analysis and fluorochrome labeling. After 60 days, the FT723 specimen exhibits the highest bone formation, suggesting it is a suitable candidate for orthopedic implant application.

Synergistic Effects of Cerium and Hot Forging on Biodegradation, Antibacterial Properties, and In Vivo Biocompatibility of Microalloyed Mg-Zr-Sr Alloys.

Biodegradable magnesium (Mg)-based alloys are potential candidates for orthopedic applications. In the present study, we have discussed the effect of cerium (Ce) addition and hot forging on mechanical properties, in vitro-in vivo corrosion, antibacterial activity, and cytocompatibility of microalloyed Mg-0.2Zr-0.1Sr-xCe (x = 0 [MZS], 0.5 wt % [MZS-Ce]) alloys. Addition of 0.5 wt % Ce to forged MZS alloys leads to strengthening of the basal texture as well as formation of a higher fraction of dynamic recrystallized (DRX) grains. Hot forging and addition of cerium to the MZS alloy improve both the yield strength and ultimate tensile strength of the forged MZS-Ce alloy by 1.39 and 1.21 times, respectively, compared to those of the forged MZS alloy. The potentiodynamic polarization test in Hank's solution indicates that the corrosion resistance of the forged MZS alloy improves with addition of 0.5 wt % Ce. Uniform distribution of Mg12Ce precipitates, a higher DRX fraction, strengthened texture, and formation of a compact CeO2 passive layer result in 1.68 times reduction in the immersion corrosion rate of the forged MZS-Ce alloy compared to that of the forged MZS alloy. Addition of Ce to the MZS alloy shows excellent antibacterial activity. The forged MZS-Ce alloy exhibited the highest antibacterial efficacy (76.73%). All the alloys show favorable cytocompatibility and alkaline phosphatase (ALP) activity with MC3T3-E1 cells. The improved corrosion resistance of the forged MZS-Ce alloy (95%) leads to higher cell viability compared to that of the forged MZS alloy (85%). In vivo biodegradation and the ability to generate new bones were analyzed by implanting cylindrical samples in the rabbit femur. Histological analysis showed no adverse effects around the implants. Gradual degradation of the implants and higher new bone formation around the forged MZS-Ce sample were confirmed by micro-CT analysis. Bone regeneration around the implants (58.21%) was validated by flurochrome labeling. After 60 days, the forged MZS-Ce alloy showed controlled corrosion and better bone-implant integration, presenting it as a potential candidate for internal fracture fixation materials.