A novel hierarchical biofunctionalized 3D-printed porous Ti6Al4V scaffold with enhanced osteoporotic osseointegration through osteoimmunomodulation.

BACKGROUND: Femoral stem of titanium alloy has been widely used for hip arthroplasty with considerable efficacy; however, the application of this implant in patients with osteoporosis is limited due to excessive bone resorption. Macrophages participate in the regulation of inflammatory response and have been a topic of increasing research interest in implant field. However, few study has explored the link between macrophage polarization and osteogenic-osteoclastic differentiation. The present study aims to develop a novel hierarchical biofunctionalized 3D-printed porous Ti6Al4V scaffold with enhanced osteoporotic osseointegration through immunotherapy. METHOD: To improve the osteointegration under osteoporosis, we developed a hierarchical biofunctionalized 3D-printed porous Ti6Al4V scaffold (PT). Biomimetic extracellular matrix (ECM) was constructed inside the interconnected pores of PT in micro-scale. And in nano-scale, a drug cargo icariin@Mg-MOF-74 (ICA@MOF) was wrapped in ECM-like structure that can control release of icariin and Mg2+. RESULTS: In this novel hierarchical biofunctionalized 3D-printed porous Ti6Al4V scaffold, the macroporous structure provides mechanical support, the microporous structure facilitates cell adhesion and enhances biocompatibility, and the nanostructure plays a biological effect. We also demonstrate the formation of abundant new bone at peripheral and internal sites after intramedullary implantation of the biofunctionalized PT into the distal femur in osteoporotic rats. We further find that the controlled-release of icariin and Mg2+ from the biofunctionalized PT can significantly improve the polarization of M0 macrophages to M2-type by inhibiting notch1 signaling pathway and induce the secretion of anti-inflammatory cytokines; thus, it significantly ameliorates bone metabolism, which contributes to improving the osseointegration between the PT and osteoporotic bone. CONCLUSION: The therapeutic potential of hierarchical PT implants containing controlled release system are effective in geriatric orthopaedic osseointegration.

Fabrication and biological evaluation of porous ß-TCP bioceramics produced using digital light processing.

Beta-tricalcium phosphate (ß-TCP) refers to one ideal bone repair substance with good biocompatibility and osteogenicity. A digital light processing (DLP)-system used in this study creates bioceramic green part by stacking up layers of photocurable tricalcium phosphate-filled slurry with various ß-TCP weight fractions. Results show that the sintering shrinkage is anisotropic and the shrinkage vertically reaches over that horizontally. The obtained porous ß-TCP parts have both macroporous outer structure and microporous inner structure, the macropore size is 400-600 µm and the micropore size is 500-1500 nm. The mechanical tests show that the porous ß-TCP bioceramic's compressive strength reaches 16.53 MPa. The cell culture confirmed that the porous ß-TCP bioceramic is capable of achieving the effective attaching, growing, and proliferating pertained to mouse osteoblast cells. This study identified considerable blood vessels and significant ectopic bone forming obviously based on the histologically-related assessment when implanting to rabbit femoral condyle deficiency for 3 months. Thus, under high bioactive property and osteoinductivity, and large precision and mechanical strength that can be adjusted, the DLP printed porous ß-TCP ceramics is capable of being promising for special uses of bones repairing.

Development of hierarchical porous bioceramic scaffolds with controlled micro/nano surface topography for accelerating bone regeneration.

Mimicking hierarchical porous architecture of bone has been considered as a valid approach to promote bone regeneration. In this study, hierarchical porous ß-tricalcium phosphate (ß-TCP) scaffolds were constructed by combining digital light processing (DLP) printing technique and in situ growth crystal process. Macro/micro hierarchical scaffolds with designed macro pores for facilitating the ingrowth of bone tissue were fabricated by DLP printing. Three types of micro/nano surface topography were obtained by in situ growth crystal process to regulate stem cells behavior. The attachment and proliferation of rat bone marrow mesenchymal stem cells (rBMSCs) were strongly dependent on the surface roughness and the specific surface area. The micro/nano surface topography distinctly facilitated the differentiation of rBMSCs by targeting MAPK, STAT and AKT signaling pathways, in which the sodium hydroxide treatment group showed the highest promoting effect. Furthermore, in vivo results of skull defect repair model of rats indicated that hierarchical scaffolds with micro/nano topographies exhibited appealing bone regeneration capacity. The hierarchical porous bioceramic scaffolds constructed by integrating structural design and physical stimulation of the external surface topography have great potential for rapid bone repair via modulation of microenvironmental regulatory pathways at the bone defect site.

Facile extrusion 3D printing of gelatine methacrylate/Laponite nanocomposite hydrogel with high concentration nanoclay for bone tissue regeneration.

The extrusion 3D printing of hydrogels has evolved as a promising approach that can be applied for specific tissue repair. However, the printing process of hydrogel scaffolds with high shape fidelity is inseparable from the complex crosslinking strategy, which significantly increases the difficulty and complexity of printing. The aim of this study was to develop a printable hydrogel that can extrude at room temperature and print scaffolds with high shape fidelity without any auxiliary crosslinking during the printing process. To this end, a novel formulation consisting of a Laponite suspension with a high solid concentration and a gelatine methacrylate (GelMA) nanocomposite hydrogel was developed. A homogeneously dispersed high-concentration (up to 20% w/v) Laponite suspension was obtained by stirring at 0 °C. The addition of Laponite with high concentration improved the rheological properties, the degradation stability, and the mechanical strength of the hydrogel. The formulation of 15% (w/v) GelMA and 8% (w/v) Laponite nanocomposite hydrogel exhibited desirable printability and biocompatibility. The GelMA/Laponite hydrogels significantly promoted bone marrow mesenchymal stem cell (BMSC) proliferation and osteogenic differentiation. Both desirable printability under mild conditions and cyto-compatibility enable composite hydrogel a potential candidate as biomaterial inks to be applied for bone tissue regeneration.

Rationally designed functionally graded porous Ti6Al4V scaffolds with high strength and toughness built via selective laser melting for load-bearing orthopedic applications.

Functionally graded materials (FGMs) with porosity variation strategy mimicking natural bone are potential high-performance biomaterials for orthopedic implants. The architecture of FGM scaffold is critical to gain the favorable combination of mechanical and biological properties for osseointegration. In this study, four types of FGM scaffolds with different structures were prepared by selective laser melting (SLM) with Ti6Al4V as building material. All the scaffolds were hollow cylinders with different three-dimensional architectures and had gradient porosity resembling the graded-porous structure of human bone. Two unit cells (diamond and honeycomb-like unit cells) were used to construct the cellular structures. Solid support structures were embedded into the cellular structures to improve their mechanical performances. The physical characteristics, mechanical properties, and deformation behaviors of the scaffolds were compared systematically. All the as-built samples with porosities of ~52-67% exhibited a radial decreasing porosity from the inner layer to the outer layer, and their pore sizes ranged from ~420 to ~630 µm. The compression tests showed the Young's moduli of all the as-fabricated samples (~3.79-~10.99 GPa) were similar to that of cortical bone. The FGM structures built by honeycomb-like unit cells with supporting structure in outer layer exhibited highest yield strength, toughness and stable mechanical properties which is more appropriate to build orthopedic scaffolds for load-bearing application.

A Novel Design of Temporomandibular Joint Prosthesis for Lateral Pterygoid Muscle Attachment: A Preliminary Study.

Introduction: In temporomandibular joint (TMJ) replacement operation, due to the condylectomy, the lateral pterygoid muscle (LPM) lost attachment and had impact on the mandible kinematic function. This study aimed to design a novel TMJ replacement prosthesis for LPM attachment and to verify its feasibility by preliminary in vitro and in vivo experiments. Materials and Methods: An artificial TMJ prosthesis designed with a porous structure on the condylar neck region for LPM attachment was fabricated by a 3D printed titanium (Ti) alloy. A rat myoblast cell line (L6) was tested for adhesion and biocompatibility with porous titanium scaffolds in vitro by cell counting Kit-8 (CCK-8), scanning electron microscope (SEM), flow cytometry (FCM), real-time quantitative polymerase chain reaction (RT-qPCR), immunocytofluorescense, western blotting, etc. The porous titanium scaffolds were further embedded in the rat intervertebral muscle to analyze muscle growth and biomechanical strength in vivo. The novel artificial TMJ prosthesis was implanted to reconstruct the goat's condyle and LPM reattachment was analyzed by hard tissue section and avulsion force test. Results: L6 muscle cells showed good proliferation potential on the porous Ti scaffold under SEM scanning and FCM test. In RT-qPCR, immunocytofluorescense and western blotting tests, the L6 cell lines had good myogenic capacity when cultured on the scaffold with high expression of factors such as Myod1 and myoglobin, etc. In the in vivo experiment, muscles penetrated into the porous scaffold in both rats and goats. In rat's intervertebral muscle implantation, the avulsion force was 0.716 N/mm2 in 4 weeks after operation and was significantly increased to 0.801 N/mm2 at 8 weeks (p < 0.05). In goat condylar reconstruction with the porous scaffold prosthesis, muscles attached to the prosthesis with the avulsion force of 0.436 N/mm2 at 8 weeks, but was smaller than the biological muscle-bone attachment force. Conclusion: The novel designed TMJ prosthesis can help LPM attach to its porous titanium scaffold structure area for future function.