SA3 - Transforming the Degradation Rate of β-tricalcium Phosphate Bone Replacement Using 3D Printers

Abstract:

Statement of the problem:
Craniofacial injuries often require resection of necrotic hard tissue. For large bone defects, autogenous bone grafting is ideal, but as is the case with all grafting procedures, is subject to limitations on quantity. Synthetic biomaterial driven three-dimensional (3D) printing technology of solid-free form fabrication (SFF) offers an alternative engineered healing approach. This research hypothesizes that a bioactive calcium-phosphate scaffold may successfully regenerate craniofacial bony defects in vivo, and that this newly formed bone will have mechanical properties similar to native bone as healing time elapses in vivo. The aim of this study was to leverage 3D printing of β-tricalcium phosphate (β-TCP), a common synthetic bone grafting material, to accelerate degradation kinetics of β-TCP while allowing for optimal bone regeneration/remodeling and bone mechanical properties.

Materials and methods:
Twenty-two 1-month-old New Zealand White rabbits underwent creation of calvarial and alveolar defects, repaired with 3D-printed β-TCP scaffolds coated with 1,000 μM of osteogenic agent dipyridamole. Rabbits were euthanized after 2, 6, and 18 months post-surgical intervention. Bone regeneration, scaffold degradation, and bone mechanical properties were quantified.

Results:
Histology analysis confirmed the generation of vascularized and organized bone. Micro CT analysis from 2 to 18 months, demonstrated decreased scaffold volume within calvarial (23.6% ±2.5%, 5.1%±2.2%; P < .001) and alveolar (21.5%±2.2%, 0.2%±1.9%; P < .001) defects, with degradation rates 54.6%/year and 90.5%/year, respectively. Scaffold-inducted bone generation within the defect was volumetrically similar to native bone in the calvarium (55.7%±6.9% vs. 46.7%±6.8%; P = .064) and alveolus (31.4%±7.1% vs. 33.8%±3.7%; P = .337). Mechanical properties between regenerated and native bone were similar.

Outcomes and conclusion:
This study demonstrates an improved degradation profile and replacement of absorbed β-TCP with vascularized, organized bone through 3D printing, and the addition of an osteogenic agent. This novel additive manufacturing and tissue-engineering protocol has implications for the future of craniofacial skeletal reconstruction as a safe and efficacious bone tissue-engineering method.

References:
Tovar N, Witek L, Atria P, Sobieraj M, Bowers M, Lopez C, Cronstein B, Coelho PG: Form and functional repair of long bone using 3D-printed bioactive scaffolds. J Tissue Eng Regen Med, 2018
Witek L, Alifarag AM, Tovar N, Lopez CD, Cronstein BN, Rodriguez ED, Coelho PG: Repair of critical-sized long bone defects using dipyridamole-augmented 3D-printed bioactive ceramic scaffolds. J Orthop Res 37(12):2499-2507, 2019