A Composite Lactide-Mineral 3D-Printed Scaffold for Bone Repair and Regeneration

Abstract

Orthopedic tumor resection, trauma, or degenerative disease surgeries can result in large bone defects and often require bone grafting. However, standard autologous bone grafting has been associated with donor site morbidity and/or limited quantity. As an alternate, allografts with or without metallic or polyether-etherketone have been used as grafting substitutes. However, these may have drawbacks as well, including stress shielding, pseudarthrosis, disease-transmission, and infection. There is therefore a need for alternative bone substitutes, such as the use of mechanically compliant three-dimensional (3D)-printed scaffolds. Several off-the-shelf materials are available for low-cost fused deposition 3D printing such as polylactic acid (PLA) and polycaprolactone (PCL). We have previously described the feasibility of 3D-printed PLA scaffolds to support cell activity and extracellular matrix deposition. In this study, we investigate two medical-grade filaments consistent with specifications found in American Society for Testing and Materials (ASTM) standard for semi-crystalline polylactide polymers for surgical implants, a pure polymer (100M) and a copolymeric material (7415) for their cytocompatibility and suitability in bone tissue engineering. Moreover, we assessed the impact on osteo-inductive properties with the addition of beta-tricalcium phosphate (β-TCP) minerals and assessed their mechanical properties. 100M and 7415 scaffolds with the additive β-TCP demonstrated superior mesenchymal stem cells (MSCs) differentiation detected via increased alkaline phosphatase activity (6-fold and 1.5-fold, respectively) and mineralized matrix deposition (14-fold and 5-fold, respectively) in vitro. Furthermore, we evaluated in vivo compatibility, biosafety and bone repair potential in a rat femur window defect model. 100M+β-TCP implants displayed a positive biosafety profile and showed significantly enhanced new bone formation compared to 100M implants evidenced by μCT (39 versus 25% bone volume/tissue volume ratio) and histological analysis 6 weeks post-implantation. These scaffolds are encouraging composite biomaterials for repairing bone applications with a great potential for clinical translation. Further analyses are required with appropriate evaluation in a larger critical-sized defect animal model with long-term follow-up.

Management of bone metastasis with zoledronic acid: A systematic review and Bayesian network meta-analysis

“…Therefore, local delivery of ZA would reduce the risk of experiencing side effects [57] , [72] . This can be achieved by using impregnated 3D-printed nanoporous scaffolds [73] . In vitro studies have shown that with a 3D-printer, it is possible to customize a model and insert it in a bone defect to allow bone marrow stem cells to infiltrate, adhere, proliferate, and form new bone [73] .…”

“…This can be achieved by using impregnated 3D-printed nanoporous scaffolds [73] . In vitro studies have shown that with a 3D-printer, it is possible to customize a model and insert it in a bone defect to allow bone marrow stem cells to infiltrate, adhere, proliferate, and form new bone [73] . Such approach showed promising results where approximately 3 µM of ZA impregnated into nanoscaffolds or beads was enough to achieve the same therapeutic concentration locally as the systemic dose of 4 mg upon intravenous administration [70] , [71] .…”

Poly(ε-caprolactone)-based nanofibrous scaffold incorporated with decellularized bone extracellular matrix as a potential strategy for bone regeneration

“…It has been estimated that there will be about 28 million orthopedic surgery procedures worldwide by 2022, and a critical issue is the demand for bone substitutes will greatly increase, which is the second most transplanted tissue annually now [37] . Due to the drawbacks of immune response, donor site morbidity and shortage of supply, it seems that autografts and allograft will not fully cover the needs of bone transplantation [38,39] . Therefore, BTE, which aims to fabricate bioactive bone scaffold for substitutions of bone tissue, is showing a promising prospect in repairing bone defect.…”

The Dual Effect of 3D-Printed Biological Scaffolds Composed of Diverse Biomaterials in the Treatment of Bone Tumors

“…In addition to assisting bioceramic or metallic particles in preparing composite scaffolds, polymers have a promising future. 100 , 101 By means of 3D printing, Ce Zhu et al prepared PEEK/graphene composite scaffolds. The scaffolds were subsequently electrophoretically deposited (EPD) with drug-loaded bioactive coatings based on hydroxyapatite (HA).…”