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3D-printed scaffold combined to 2D osteoinductive coatings to repair a critical-size mandibular bone defect.

ABSTRACT: The reconstruction of large bone defects (12 cm³) remains a challenge for clinicians. We developed a new critical-size mandibular bone defect model on a minipig, close to human clinical issues. We analyzed the bone reconstruction obtained by a 3D-printed scaffold made of clinical-grade polylactic acid (PLA), coated with a polyelectrolyte film delivering an osteogenic bioactive molecule (BMP-2). We compared the results (computed tomography scans, microcomputed tomography scans, histology) to the gold standard solution, bone autograft. We demonstrated that the dose of BMP-2 delivered from the scaffold significantly influenced the amount of regenerated bone and the repair kinetics, with a clear BMP-2 dose-dependence. Bone was homogeneously formed inside the scaffold without ectopic bone formation. The bone repair was as good as for the bone autograft. The BMP-2 doses applied in our study were reduced 20- to 75-fold compared to the commercial collagen sponges used in the current clinical applications, without any adverse effects. Three-dimensional printed PLA scaffolds loaded with reduced doses of BMP-2 may be a safe and simple solution for large bone defects faced in the clinic.

SUBMITTER: Bouyer M

PROVIDER: S-EPMC8173095 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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3D-printed scaffold combined to 2D osteoinductive coatings to repair a critical-size mandibular bone defect.

Bouyer M M Garot C C Machillot P P Vollaire J J Fitzpatrick V V Morand S S Boutonnat J J Josserand V V Bettega G G Picart C C

Materials today. Bio 20210504

The reconstruction of large bone defects (12 cm<sup>3</sup>) remains a challenge for clinicians. We developed a new critical-size mandibular bone defect model on a minipig, close to human clinical issues. We analyzed the bone reconstruction obtained by a 3D-printed scaffold made of clinical-grade polylactic acid (PLA), coated with a polyelectrolyte film delivering an osteogenic bioactive molecule (BMP-2). We compared the results (computed tomography scans, microcomputed tomography scans, histolo ...[more]

PMID: 34124641

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Project description:The process of bone regeneration is complicated, and it is still a major clinical challenge to regenerate critical-size bone defects caused by severe trauma, infection, and tumor resection. Intracellular metabolism has been found to play an important role in the cell fate decision of skeletal progenitor cells. GW9508, a potent agonist of the free fatty acid receptors GPR40 and GPR120, appears to have a dual effect of inhibiting osteoclastogenesis and promoting osteogenesis by regulating intracellular metabolism. Hence, in this study, GW9508 was loaded on a scaffold based on biomimetic construction principles to facilitate the bone regeneration process. Through 3D printing and ion crosslinking, hybrid inorganic-organic implantation scaffolds were obtained after integrating 3D-printed β-TCP/CaSiO3 scaffolds with a Col/Alg/HA hydrogel. The 3D-printed β-TCP/CaSiO3 scaffolds had an interconnected porous structure that simulated the porous structure and mineral microenvironment of bone, and the hydrogel network shared similar physicochemical properties with the extracellular matrix. The final osteogenic complex was obtained after GW9508 was loaded into the hybrid inorganic-organic scaffold. To investigate the biological effects of the obtained osteogenic complex, in vitro studies and a rat cranial critical-size bone defect model were utilized. Metabolomics analysis was conducted to explore the preliminary mechanism. The results showed that 50 μM GW9508 facilitated osteogenic differentiation by upregulating osteogenic genes, including Alp, Runx2, Osterix, and Spp1 in vitro. The GW9508-loaded osteogenic complex enhanced osteogenic protein secretion and facilitated new bone formation in vivo. Finally, the results from metabolomics analysis suggested that GW9508 promoted stem cell differentiation and bone formation through multiple intracellular metabolism pathways, including purine and pyrimidine metabolism, amino acid metabolism, glutathione metabolism, and taurine and hypotaurine metabolism. This study provides a new approach to address the challenge of critical-size bone defects.

Project description:Conventional plate osteosynthesis of critical-sized bone defects in canine mandibles can fail to restore former functionality and stability due to adaption limits. Three-dimensional (3D) printed patient-specific implants are becoming increasingly popular as these can be customized to avoid critical structures, achieve perfect alignment to individual bone contours, and may provide better stability. Using a 3D surface model for the mandible, four plate designs were created and evaluated for their properties to stabilize a defined 30 mm critical-size bone defect. Design-1 was manually designed, and further shape optimized using Autodesk ® Fusion 360 (ADF360) and finite element analysis (FE) to generate Design-2. Design-4 was created with the generative design (GD) function from ADF360 using preplaced screw terminals and loading conditions as boundaries. A 12-hole reconstruction titanium locking plate (LP) (2.4/3.0 mm) was also tested, which was scanned, converted to a STL file and 3D printed (Design-3). Each design was 3D printed from a photopolymer resin (VPW) and a photopolymer resin in combination with a thermoplastic elastomer (VPWT) and loaded in cantilever bending using a customized servo-hydraulic mechanical testing system; n = 5 repetitions each. No material defects pre- or post-failure testing were found in the printed mandibles and screws. Plate fractures were most often observed in similar locations, depending on the design. Design-4 has 2.8-3.6 times ultimate strength compared to other plates, even though only 40% more volume was used. Maximum load capacities did not differ significantly from those of the other three designs. All plate types, except D3, were 35% stronger when made of VPW, compared to VPWT. VPWT D3 plates were only 6% stronger. Generative design is faster and easier to handle than optimizing manually designed plates using FE to create customized implants with maximum load-bearing capacity and minimum material requirements. Although guidelines for selecting appropriate outcomes and subsequent refinements to the optimized design are still needed, this may represent a straightforward approach to implementing additive manufacturing in individualized surgical care. The aim of this work is to analyze different design techniques, which can later be used for the development of implants made of biocompatible materials.

Dataset Information

3D-printed scaffold combined to 2D osteoinductive coatings to repair a critical-size mandibular bone defect.

Publications

3D-printed scaffold combined to 2D osteoinductive coatings to repair a critical-size mandibular bone defect.

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