Cryogenic 3D printing of dual-delivery scaffolds for improved bone regeneration with enhanced vascularization

Abstract

Three-dimensional (3D) printing has been increasingly employed to produce advanced bone tissue engineering scaffolds with biomimetic structures and matched mechanical strengths, in order to induce improved bone regeneration in defects with a critical size. Given that the successful bone regeneration requires both excellent osteogenesis and vascularization, endowing scaffolds with both strong bone forming ability and favorable angiogenic potential would be highly desirable to induce improved bone regeneration with required vascularization. In this investigation, customized bone tissue engineering scaffolds with balanced osteoconductivity/osteoinductivity were produced via cryogenic 3D printing of β-tricalcium phosphate and osteogenic peptide (OP) containing water/poly(lactic- co -glycolic acid)/dichloromethane emulsion inks. The fabricated scaffolds had a hierarchically porous structure and were mechanically comparable to human cancellous bone. Angiogenic peptide (AP) containing collagen I hydrogel was then coated on scaffold surface to further provide scaffolds with angiogenic capability. A sequential release with a quick AP release and a slow but sustained OP release was obtained for the scaffolds. Both rat endothelial cells (ECs) and rat bone marrow derived mesenchymal stem cells (MSCs) showed high viability on scaffolds. Improved in vitro migration and angiogenesis of ECs were obtained for scaffolds delivered with AP while enhanced osteogenic differentiation was observed in scaffolds containing OP. The in vivo results showed that, toward scaffolds containing both AP and OP, the quick release of AP induced obvious angiogenesis in vivo , while the sustained OP release significantly improved the new bone formation. This study provides a facile method to produce dual-delivery scaffolds to achieve multiple functions.

Clinical Application of Bone Marrow Mesenchymal Stem/Stromal Cells to Repair Skeletal Tissue

“…Other examples include the development of bioglass functionalized gelatin nanofibrous scaffolds, which promoted ectopic bone formation in rats [ 64 ], and the use of the BMSC derived extracellular matrix in combination with a 3D-printed HA scaffold to promote strong osteogenic ability and appropriate “tissue-space” structure [ 82 ]. Furthermore, researchers have also suggested bone synthesis can be improved via a biphasic dual delivery scaffold systems [ 83 , 84 ]. More specifically one approach used a system containing two scaffolds, one consisted of a Collagen type I hydrogel that was overlaid onto the surface of the other beta-TCP (β-TCP) scaffold.…”

“…More specifically one approach used a system containing two scaffolds, one consisted of a Collagen type I hydrogel that was overlaid onto the surface of the other beta-TCP (β-TCP) scaffold. The β-TCP scaffold contained a slow release of osteogenic peptide (functionally synthesized equivalent of bone morphogenetic protein-2 (BMP-2)), while the hydrogel was loaded with a quick release angiogenic peptide (functionally synthesized equivalent of vascular endothelial growth factor (VEGF)), thus appropriately influencing both osteogenesis and angiogenesis, respectively [ 84 ]. In the preclinical setting others are investigating the multifactorial approach of utilizing hMSC in conjunction with endothelial progenitor cells cultured within a macroporous scaffold under “dynamic conditions” in a biaxial bioreactor prior to sub-cutaneous transplantation in immunocompromised mice.…”

An overview of polyester/hydroxyapatite composites for bone tissue repairing

“…Materials fabricated by 3DP technique have the following advantages: customized pore size/porosity, tailored shape and tunable mechanical properties, etc. [ 58 ]. Thus, it is an attractive and promising technology in the fabrication of bone repairing materials [ 59 ].…”

Application of 3D Printing in Implantable Medical Devices

“…3D printing is also known as additive manufacturing; it is done through layer-by-layer stacking techniques, and according to the designed 3D model, complex and diverse physical entities can be manufactured [ 4 ]. Common manufacturing processes for 3D printing include Stereo Lithography Apparatus (SLA) [ 5 ], Laminated Object Manufacturing (LOM) [ 6 ], Selective laser Sintering (SLS) [ 7 ], Fused Deposition Modeling (FDM) [ 8 ], and Three-Dimensional Printing (3DP) [ 9 ].…”