Bone tissue regeneration:The role of finely tuned pore architecture of bioactive scaffolds before clinical translation

Spatial dimension of pores and interconnection in macroporous scaffolds is of particular importance in facilitating endogenous cell migration and bone tissue ingrowth.However,it is still a challenge to widely tune structure parameters of scaffolds by conventional methods because of inevitable pore geometrical deformation and poor pore interconnectivity.Here,the long-term in vivo biological performances of nonstoichiometric bioceramic scaffolds with different pore dimensions were assessed in critical-size femoral bone defect model.The 6%Mg-substituted wollastonite(CSi-Mg6)powders were prepared via wet-chemical precipitation and the scaffolds elaborately printed by ceramic stereolithography,displaying designed constant pore strut and tailorable pore height(200,320,450,600μm),were investigated thoroughly in the bone regeneration process.Together with detailed structural stability and mechanical properties were collaboratively outlined.BothμCT and histological analyses indicated that bone tissue ingrowth was retarded in 200μm scaffolds in the whole stage(2-16 weeks)but the 320μm scaffolds showed appreciable bone tissue in the center of porous constructs at 6-10 weeks and matured bone tissue were uniformly invaded in the whole pore networks at 16 weeks.Interestingly,the neo-tissue ingrowth was facilitated in the 450μm and 600μm scaffolds after 2 weeks and higher extent of bone regeneration and remodeling at the later stage.These new findings provide critical information on how engineered porous architecture impact bone regeneration in vivo.Simultaneously,this study shows important implications for optimizing the porous scaffolds design by advanced additive manufacture technique to match the clinical translation with high performance.

3D printing of Mg-substituted wollastonite reinforcing diopside porous bioceramics with enhanced mechanical and biological performances

Mechanical strength and its long-term stability of bioceramic scaffolds is still a problem to treat the osteonecrosis of the femoral head.Considering the long-term stability of diopside(DIO)ceramic but poor mechanical strength,we developed the DIO-based porous bioceramic composites via dilute magnesium substituted wollastonite reinforcing and three-dimensional(3D)printing.The experimental results showed that the secondary phase(i.e.10%magnesium substituting calcium silicate;CSM10)could readily improve the sintering property of the bioceramic composites(DIO/CSM10-x,x=0-30)with increasing the CSM10 content from 0%to 30%,and the presence of the CSM10 also improved the biomimetic apatite mineralization ability in the pore struts of the scaffolds.Furthermore,the flexible strength(12.5 -30 MPa)and compressive strength(14-37 MPa)of the 3D printed porous bioceramics remarkably increased with increasing CSM10 content,and the compressive strength of DIO/CSM10-30 showed a limited decay(from 37 MPa to 29 MPa)in the Tris buffer solution for a long time stage(8 weeks).These findings suggest that the new CSM10-reinforced diopside porous constructs possess excellent mechanical properties and can potentially be used to the clinic,especially for the treatment of osteonecrosis of the femoral head work as a bioceramic rod.

Integrating pore architectures to evaluate vascularization efficacy in silicate-based bioceramic scaffolds

Pore architecture in bioceramic scaffolds plays an important role in facilitating vascularization efficiency during bone repair or orbital reconstruction.Many investigations have explored this relationship but lack integrating pore architectural features in a scaffold,hindering optimization of architectural parameters(geometry,size and curvature)to improve vascularization and consequently clinical outcomes.To address this challenge,we have developed an integrating design strategy to fabricate different pore architectures(cube,gyroid and hexagon)with different pore dimensions(-350,500 and 650 lm)in the silicate-based bioceramic scaffolds via digital light processing technique.The sintered scaffolds maintained high-fidelity pore architectures similar to the printing model.The hexagon-and gyroid-pore scaffolds exhibited the highest and lowest compressive strength(from 15 to 55MPa),respectively,but the cube-pore scaffolds showed appreciable elastic modulus.Moreover,the gyroid-pore architecture contributed on a faster ion dissolution and mass decay in vitro.It is interesting that bothμCT and histological analyses indicate vascularization efficiency was challenged even in the 650-μm pore region of hexagon-pore scaffolds within 2weeks in rabbit models,but the gyroid-pore constructs indicated appreciable blood vessel networks even in the 350-μm pore region at 2weeks and high-density blood vessels were uniformly invaded in the 500-and 650-μm pore at 4weeks.Angiogenesis was facilitated in the cube-pore scaffolds in comparison with the hexagon-pore ones within 4weeks.These studies demonstrate that the continuous pore wall curvature feature in gyroid-pore architecture is an important implication for biodegradation,vascular cell migration and vessel ingrowth in porous bioceramic scaffolds.