Vitamin D3 Release from MgO Doped 3D Printed TCP Scaffolds for Bone Regeneration.

Regenerating bone tissue in critical-sized craniofacial bone defects remains challenging and requires the implementation of innovative bone implants with early stage osteogenesis and blood vessel formation. Vitamin D3 is incorporated into MgO-doped 3D-printed scaffolds for defect-specific and patient-specific implants in low load-bearing areas. This novel bone implant also promotes early stage osteogenesis and blood vessel development. Our results show that vitamin D3-loaded MgO-doped 3D-printed scaffolds enhance osteoblast cell proliferation 1.3-fold after being cultured for 7 days. Coculture studies on osteoblasts derived from human mesenchymal stem cells (hMSCs) and osteoclasts derived from monocytes show the upregulation of genes related to osteoblastogenesis and the downregulation of RANK-L, which is essential for osteoclastogenesis. Release of vitamin D3 also inhibits osteoclast differentiation by 1.9-fold after a 21-day culture. After 6 weeks, vitamin D3 release from MgO-doped 3D-printed scaffolds enhances the new bone formation, mineralization, and angiogenic potential. The multifunctional 3D-printed scaffolds can improve early stage osteogenesis and blood vessel formation in craniofacial bone defects.

Hydroxyapatite coated titanium with curcumin and epigallocatechin gallate for orthopedic and dental applications.

Titanium and its alloy are clinically used as an implant material for load-bearing applications to treat bone defects. However, the lack of biological interaction between bone tissue and implant and the risk of infection are still critical challenges in clinical orthopedics. In the current work, we have developed a novel approach by first 1) modifying the implant surface using hydroxyapatite (HA) coating to enhance bioactivity and 2) integrating curcumin and epigallocatechin gallate (EGCG) in the coating that would induce chemopreventive and osteogenic potential and impart antibacterial properties to the implant. The study shows that curcumin and EGCG exhibit controlled and sustained release profiles in acidic and physiological environments. Curcumin and EGCG also show in vitro cytotoxicity toward osteosarcoma cells after 11 days, and the dual system shows a ~94 % reduction in bacterial growth, indicating their in vitro chemopreventive potential and antibacterial efficacy. The release of both curcumin and EGCG was found to be compatible with osteoblast cells and further promotes their growth. It shows a 3-fold enhancement in cellular viability in the dual drug-loaded implant compared to the untreated samples. These findings suggest that multifunctional HA-coated Ti6Al4V implants integrated with curcumin and EGCG could be a promising strategy for osteosarcoma inhibition and osteoblast cell growth while preventing infection.

Micelle encapsulated curcumin and piperine-laden 3D printed calcium phosphate scaffolds enhance in vitro biological properties.

Limitations in the current clinical management of critical-sized osseous defects have driven the need for multifunctional bone constructs. The ideal bone scaffold should possess advanced microarchitecture, well-defined pore interconnectivity, and supply biological signals, which actively guide and control tissue regeneration while simultaneously preventing post-implantation complications. Here, a natural medicine-based localized drug delivery from 3D printed scaffold is presented, which offers controlled release of curcumin, piperine from nano-sized polymeric micelles, and burst release of antibacterial carvacrol from the coating endowing the scaffold with their distinct, individual biological properties. This functionalized scaffold exhibits improved osteoblast (hFOB) cell attachment, 4-folds higher hFOB proliferation, and 73% increased hFOB differentiation while simultaneously providing cytotoxicity towards osteosarcoma cells with 61% lesser viability compared to control. In vitro, early tube formation (p < 0.001) indicates that the scaffolds can modulate the endothelial cellular network, critical for faster wound healing. The scaffold also exhibits 94% enhanced antibacterial efficacy (p < 0.001) against gram-positive Staphylococcus aureus, the main causative bacteria for osteomyelitis. Together, the multifunctional scaffolds provide controlled delivery of natural biomolecules from the nano-sized micelle-loaded 3D printed matrix for significant improvement in osteoblast proliferation, endothelial formation, osteosarcoma, and bacterial inhibition, guiding better bone regeneration for post-traumatic defect repair.