Three-dimensionally printed polyetherketoneketone scaffolds with mesenchymal stem cells for the reconstruction of critical-sized mandibular defects.

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 < 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. LEVEL OF EVIDENCE: NA. Laryngoscope, 127:E392-E398, 2017.

Improving PEEK bioactivity for craniofacial reconstruction using a 3D printed scaffold embedded with mesenchymal stem cells.

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/cm(2). 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 < 0.05). 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.