No current clinical treatments provide an ideal long‐term solution for repair of long bone segment defects. Incomplete healing prevents patients from returning to preinjury activity and ultimately requires additional surgery to induce healing. Obtaining autologous graft material is costly, incurs morbidity, requires surgical time, and quality material is finite. In this pilot study, 3D printed biomimetic scaffolds were used to facilitate rapid bone bridging in critical sized defects in a sheep model. An inverse trabecular pattern based on micro‐CT scans of sheep trabecular bone was printed in polybutylene terephthalate. Scaffolds were coated with micron‐sized tricalcium phosphate particles to induce osteoconductivity. Mesenchymal stem cells (MSCs) were isolated from sheep inguinal and tail fat, in one group of sheep and scaffolds were infiltrated with MSCs in a bioreactor. Controls did not undergo surgery for cell extraction. Scaffolds were implanted into two experimental and two control adult sheep, and followed for either 3 or 6 months. Monthly radiographs and post explant micro‐CT scanning demonstrated bone formation on the lateral, anterior, medial, and posterior‐medial aspects along the entire length of the defect. Bone formation was absent on the posterior‐lateral aspect where a muscle is generally attached to the bone. The 3‐month time point showed 15.5% more cortical bone deposition around the scaffold circumference while the 6‐month time point showed 40.9% more bone deposition within scaffold pores. Control sheep failed to unite. Serum collagen type‐1C‐terminus telopeptides (CTX‐1) showed time‐dependent levels of bone resorption, and calcein labeling demonstrated an increase in bone formation rate in treated animals compared with controls. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 242–252, 2019.
Achieving adequate healing in large or load‐bearing bone defects is highly challenging even with surgical intervention. The clinical standard of repairing bone defects using autografts or allografts has many drawbacks. A bioactive ceramic scaffold, strontium‐hardystonite‐gahnite or “Sr‐HT‐Gahnite” (a multi‐component, calcium silicate‐based ceramic) is developed, which when 3D‐printed combines high strength with outstanding bone regeneration ability. In this study, the performance of purely synthetic, 3D‐printed Sr‐HT‐Gahnite scaffolds is assessed in repairing large and load‐bearing bone defects. The scaffolds are implanted into critical‐sized segmental defects in sheep tibia for 3 and 12 months, with bone autografts used for comparison. The scaffolds induce substantial bone formation and defect bridging after 12 months, as indicated by X‐ray, micro‐computed tomography, and histological and biomechanical analyses. Detailed analysis of the bone‐scaffold interface using focused ion beam scanning electron microscopy and multiphoton microscopy shows scaffold degradation and maturation of the newly formed bone. In silico modeling of strain energy distribution in the scaffolds reveal the importance of surgical fixation and mechanical loading on long‐term bone regeneration. The clinical application of 3D‐printed Sr‐HT‐Gahnite scaffolds as a synthetic bone substitute can potentially improve the repair of challenging bone defects and overcome the limitations of bone graft transplantation.more » « less
- NSF-PAR ID:
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Healthcare Materials
- Medium: X
- Sponsoring Org:
- National Science Foundation
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