Mesenchymal stem cell seeded, biomimetic 3D printed scaffolds induce complete bridging of femoral critical sized defects

Abstract

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, 2018.

The Regenerative Applicability of Bioactive Glass and Beta-Tricalcium Phosphate in Bone Tissue Engineering: A Transformation Perspective

“…In another study, 3D printed polybutylene terephthalate scaffolds coated with micro-size β-TCP were infiltrated with endogenous mesenchymal stem cell and grown in a bioreactor and successfully facilitated the bridging of femoral critical size defects (42 mm). This phenomenon was not observed in grafts free of mesenchymal stem cell and β-TCP, which validates their role in regeneration [95]. Elsewhere, others have shown the application of N-hydroxysuccinimide as an adhesive material [96].…”

New Application of Osteogenic Differentiation from HiPS Stem Cells for Evaluating the Osteogenic Potential of Nanomaterials in Dentistry

“…The ability of induced pluripotent stem cells (HiPS) to be reprogrammed from human tissue and to differentiate into the three embryonic sheets was discovered by Yamanaka in 2006 [17]. Several studies mentioned the reprogramming of cells in the laboratory from cells of oral origin, which have proliferative potential [18][19][20]. Therefore, this type of stem cell has potential for use in personalized medicine in terms of tissue engineering applied to the regeneration of oral tissues; in practical terms, this means stem cells could be combined with scaffold, biomaterials, and/or nanomaterials and growth factors to regenerate alveolar bone [21].…”

Advancements in Therapeutics via 3D Printed Multifunctional Architectures from Dispersed 2D Nanomaterial Inks

“…[33] Patients with osteosarcoma generally lose self-healing ability after major surgery which leads to serious bone defects. [33,269,270] To address such lingering issues of bone defects, tardy bone tissue regeneration and long-term pain, 2D Ti 3 C 2 in combination with 3D printed scaffolds of bioactive glass (BG) are implemented. The 2D Ti 3 C 2 MXenes act as agents for killing tumor through photonic therapy, and simultaneously aids in promoting the bone tissue regeneration (Figure 9).…”