“Bone Tissue Engineering in the Growing Calvaria: A 3D Printed Bioceramic Scaffold to Reconstruct Critical-Sized Defects in a Skeletally Immature Pig Model”

Abstract

Background: Three-dimensional printed bioceramic scaffolds composed of 100% β-tricalcium phosphate augmented with dipyridamole (3DPBC-DIPY) can regenerate bone across critically sized defects in skeletally mature and immature animal models. Before human application, safe and effective bone formation should be demonstrated in a large translational animal model. This study evaluated the ability of 3DPBC-DIPY scaffolds to restore critically sized calvarial defects in a skeletally immature, growing minipig. Methods: Unilateral calvarial defects (~1.4 cm) were created in 6-week-old Göttingen minipigs (n = 12). Four defects were filled with a 1000 μm 3DPBC-DIPY scaffold with a cap (a solid barrier on the ectocortical side of the scaffold to prevent soft-tissue infiltration), four defects were filled with a 1000 μm 3DPBC-DIPY scaffold without a cap, and four defects served as negative controls (no scaffold). Animals were euthanized 12 weeks postoperatively. Calvariae were subjected to micro–computed tomography, 3D reconstruction with volumetric analysis, qualitative histologic analysis, and nanoindentation. Results: Scaffold-induced bone growth was statistically greater than in negative controls (P ≤ 0.001), and the scaffolds with caps produced significantly more bone generation compared with the scaffolds without caps (P ≤ 0.001). Histologic analysis revealed woven and lamellar bone with haversian canals throughout the regenerated bone. Cranial sutures were observed to be patent, and there was no evidence of ectopic bone formation or excess inflammatory response. Reduced elastic modulus and hardness of scaffold-regenerated bone were found to be statistically equivalent to native bone (P = 0.148 for reduced elastic modulus of scaffolds with and without caps and P = 0.228 and P = 0.902 for hardness of scaffolds with and without caps, respectively). Conclusion: 3DPBC-DIPY scaffolds have the capacity to regenerate bone across critically sized calvarial defects in a skeletally immature translational pig model. Clinical Relevance Statement: This study assessed the bone generative capacity of 3D-printed bioceramic scaffolds composed of 100% β-tricalcium phosphate and augmented with dipyridamole placed within critical-sized calvarial defects in a growing porcine model.

Bone Tissue Engineering (BTE) of the Craniofacial Skeleton, Part II: Translational Potential of 3D-Printed Scaffolds for Defect Repair

“…4). 59 This is the first study to report use of such BTE construct in a growing swine model, with similar bone morphology, repair, and wound healing to humans compared with previous skeletally immature models 40–42 . Still, this study is limited by the shorter endpoint, 12 weeks, utilization of a non–load-bearing defect, and lack of comparison to the standard-of-care, autologous graft 59 .…”

“…Most recently, the effectiveness of 3D-printed normalβ -TCP scaffolds in regenerating pediatric craniofacial defects has been reported in skeletally immature, 5-week-old Göttingen minipigs. Critical-sized calvaria defects were filled with 1000 normalμ M 3DBC-DIPY scaffold with a porous or solid cap (soft tissue infiltrative barrier) compared with negative control (no scaffold) 59 . After 12 weeks, scaffold-induced bone growth was greater than the negative control, with significantly greater bone formation in the defects repaired with solid caps versus porous-capped scaffolding due to the minimization of soft tissue infiltration (Fig.…”

Bone Tissue Engineering (BTE) of the Craniofacial Skeleton, Part I: Evolution and Optimization of 3D-Printed Scaffolds for Repair of Defects

“…Complex 3D-printed scaffolds (Fig. 3C) have been reported to mimic the external and internal architecture of the host site and provide a template for cell attachment and migration 10,11,14,24,83 . Compared to conventional particulate bone grafts, 3D-printed scaffolds provide an improved structural stability to the wound bed.…”

“…3C) have been reported to mimic the external and internal architecture of the host site and provide a template for cell attachment and migration. 10,11,14,24,83 Compared to conventional particulate bone grafts, 3D-printed scaffolds provide an improved structural stability to the wound bed. This reestablishes tissue architecture and allows for an organized arrangement for the progression of bone formation with its accompanying vascular supply.…”

“…81 Recently, synthetic scaffold bioactivity has shown to be augmented via loading of scaffolds with osteogenic cells and/or growth factors under different protocols, which may improve bone formation and accelerate the healing process. CAD rendering (isometric and top views) and non-decalcified histological sections of high fidelity fit-and-fill scaffolds for treatment of defects in the (A1, A2, A3) calvaria, 83 (B1, B2, B3) ramus, 15 (C1, C2, C3) alveolus 36 (alternating green and orange layers represent an orthogonal layering pattern during sequential, layer-by-layer deposition of β-TCP colloidal ink (not to scale)). and (D1, D2, D3) mandible (I = incisor; T = tooth; IAN = inferior alveolar nerve) -green and orange layers represent primary printing material (β-TCP) and fugitive support material (Carbon Black), respectively.…”