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Objective Additive manufacturing offers a tailored approach to tissue engineering by providing anatomically precise scaffolds onto which stem cells and growth factors can be supplied. Polyetherketoneketone (PEKK), an ideal candidate biomaterial, is limited by a poor implant–bone interface but can be functionalized with adipose-derived stem cells (ADSC) to promote integration. This in vivo study examined the interaction of a three-dimensional printed PEKK/ADSC implant within the critical-sized mandibular defect in a rabbit model. Study Design/Methods Trapezoidal porous scaffolds with dimensions of 1.5 × 1.0 × 0.5 cm were printed using selective laser sintering. ADSCs were seeded on the scaffolds that were then implanted in marginal defects created in New Zealand rabbits. Rabbits were euthanized at 10- and 20-week intervals. Microcomputed tomography was used to characterize bone ingrowth and was correlated with histological analysis. Stress testing was performed on the scaffolds before and after implantation. Results All scaffolds were well integrated into adjacent bone. Bone-to-tissue volume increased from 30.34% ( ± 12.46) to 61.27% ( ± 8.24), and trabecular thickness increased from 0.178 mm ( ± 0.069) to 0.331 mm ( ± 0.0306) in the 10- and 20-week groups, respectively, compared to no bone regrowth on the control side (P

Objective Polyetheretherketone (PEEK) is a bioinert thermoplastic that has been investigated for its potential use in craniofacial reconstruction; however, its use in clinical practice is limited by a poor integration with adjacent bone upon implantation. To improve the bone–implant interface, two strategies have been employed: to modify its surface or to impregnate PEEK with bioactive materials. This study attempts to combine and improve upon the two approaches by modifying the internal structure into a trabecular network and to impregnate PEEK with mesenchymal stem cells. Furthermore, we compare the newly designed PEEK scaffolds' interactions with both bone-derived (BMSC) and adipose (ADSC) stem cells. Design Customized PEEK scaffolds were designed to incorporate a trabecular microstructure using a computer-aided design program and then printed via selective laser sintering (SLS), a 3D-printing process with exceptional accuracy. The scaffold structure was evaluated using microCT. Scanning electron microscopy (SEM) was used to evaluate scaffold morphology with and without mesenchymal stem cells (MSCs). Adipose and bone marrow mesenchymal cells were isolated from rats and cultured on scaffolds. Cell proliferation and differentiation were assessed using alamarBlue and alkaline phosphatase assays, respectively. Cell morphology after one week of co-culturing cells with PEEK scaffolds was evaluated using SEM. Results SLS 3D printing fabricated scaffolds with a porosity of 36.38% ± 6.66 and density of 1.309 g/cm2. Cell morphology resembled viable fibroblasts attaching to the surface and micropores of the scaffold. PEEK scaffolds maintained the viability of both ADSCs and BMSCs; however, ADSCs demonstrated higher osteodifferentiation than BMSCs ( p Conclusions This study demonstrates for the first time that SLS 3D printing can be used to fabricate customized porous PEEK scaffolds that maintain the viability of adipose and bone marrow-derived MSCs and induce the osteodifferentiation of the adipose-derived MSCs. The combination of 3D printed PEEK scaffolds with MSCs could overcome some of the limitations using PEEK biopolymers for load-bearing bone regeneration in craniofacial reconstruction.

Background and Objective. Dental stem cell-based tissue engineered constructs are emerging as a promising alternative to autologous bone transfer for treating bone defects. The purpose of this review is to systematically assess the preclinical in vivo and in vitro studies which have evaluated the efficacy of dental stem cells on bone regeneration.Methods. A literature search was conducted in Ovid Medline, Embase, PubMed, and Web of Science up to October 2014. Implantation of dental stem cells in animal models for evaluating bone regeneration and/or in vitro studies demonstrating osteogenic potential of dental stem cells were included. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were used to ensure the quality of the search. Modified ARRIVE (Animal research: reporting in invivo experiments) and CONSORT (Consolidated reporting of trials) were used to critically analyze the selected studies.Results. From 1914 citations, 207 full-text articles were screened and 137 studies were included in this review. Because of the heterogeneity observed in the studies selected, meta-analysis was not possible.Conclusion. Both in vivo and in vitro studies indicate the potential use of dental stem cells in bone regeneration. However well-designed randomized animal trials are needed before moving into clinical trials.

Additive manufacturing offers a tailored approach to tissue engineering by providing anatomically precise scaffolds onto which stem cells and growth factors can be supplied. Polyetherketoneketone (PEKK), an ideal candidate biomaterial, is limited by a poor implant-bone interface but can be functionalized with adipose-derived stem cells (ADSC) to promote integration. This in vivo study examined the interaction of a three-dimensional printed PEKK/ADSC implant within the critical-sized mandibular defect in a rabbit model.Trapezoidal porous scaffolds with dimensions of 1.5 × 1.0 × 0.5 cm were printed using selective laser sintering. ADSCs were seeded on the scaffolds that were then implanted in marginal defects created in New Zealand rabbits. Rabbits were euthanized at 10- and 20-week intervals. Microcomputed tomography was used to characterize bone ingrowth and was correlated with histological analysis. Stress testing was performed on the scaffolds before and after implantation.All scaffolds were well integrated into adjacent bone. Bone-to-tissue volume increased from 30.34% ( ± 12.46) to 61.27% ( ± 8.24), and trabecular thickness increased from 0.178 mm ( ± 0.069) to 0.331 mm ( ± 0.0306) in the 10- and 20-week groups, respectively, compared to no bone regrowth on the control side (P 0.05). Histology confirmed integration at the bone-implant interface. Biomechanical testing revealed a compressive resistance 15 times that of bone alone (P 0.05) CONCLUSION: 3D-printed PEKK scaffolds combined with ADSCs present a promising solution to improve the bone-implant interface and increase the resistance to forces of mastication after mandibular reconstruction.NA. Laryngoscope, 127:E392-E398, 2017.

Multipotent mesenchymal stromal cells (MSC) derived from both the bone marrow and adipose tissue possess the ability to differentiate into multiple cell lineages, regulate the immune function by secreting numerous bioactive paracrine factors, and hold great potential in cell therapy and tissue engineering. When combined with three-dimensional (3D) scaffolds, MSC can be used for bone defect reconstruction and engineering. This protocol describes the isolation of bone marrow mesenchymal stromal cells (BMMSC) and adipose-tissue derived stem cells (ADSC) from rabbits for subsequent seeding on tissue-engineered 3D-printed scaffolds and transplantation into a rabbit-model with the goal of repairing large osseous mandibular defects (one quarter of the lower jaw is removed surgically). Steps to demonstrate the three cell differentiation lineage potentials of BMMSC and ADSC into osteocytes, adipocytes, and chondrocytes are described. A modified cell seeding method using syringes on scaffold is detailed. Creating a large mandibular bone defect, the rapid prototyping method to print a customized 3D-scaffold, the scaffold implantation procedure in rabbits, and microcomputed tomography (micro-CT) analysis are also described.