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.
Highlights
Bone is one of the most transplanted types of tissues (Brantigan and Steffee, 1993; Gómez et al, 2016) with more than 2 million bone grafting procedures annually in different surgical fields (Giannoudis et al, 2005)
It is clear that the addition of betatricalcium phosphate (β-TCP) particles had a significant impact on weight (100M: 240.6 mg ± 1.5 standard deviation (SD), pure lactide polymer (100M)+β-TCP: 301 mg ± 4.5 SD, 7415: 216 mg ± 2 SD, 7415+β-TCP: 228 mg ± 0.8 SD) (P-value < 0.05 to
In order to evaluate the changes in material properties as a consequence of thermal exposure during 3D printing, differential scanning calorimetry (DSC), gel permeation chromatography (GPC), and gas chromatography (GC) analysis were conducted including the molar composition, molecular weights, and thermal properties of 3Dprinted scaffolds (Table 1)
Summary
Bone is one of the most transplanted types of tissues (Brantigan and Steffee, 1993; Gómez et al, 2016) with more than 2 million bone grafting procedures annually in different surgical fields (Giannoudis et al, 2005). For long bones and spine reconstruction, metallic implants with allografts show positive short-term results, have high mechanical strength and reduce the need for autografts. There is emergence of magnesium based degradable implants, current metallic implants are considered as permanent foreign bodies within the host, which may eventually require a secondary removal intervention (Glassman et al, 1996). Due to such shortcomings, there is a need to develop new innovative materials which possess mechanical strength, are bioresorbable and promote bone regeneration with better understanding for bone healing and clinical applicability
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