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International Journal of Bioprinting                             Implantation of composites for cartilage repair




























            Figure 3. In vitro screening of pMSC donors. (Left to right) Compressive modulus and biochemical contents (DNA, sulfated glycosaminoglycan (sGAG),
            and collagen (COL) contents) of composites containing encapsulated adult pMSCs from 3 donors and cultured for 28 days in chondrogenic media. n = 4,
            one-way ANOVA with Tukey’s HSD post-hoc test, *p < 0.05, ns = not significant.
            n = 6), pinned precultured composites (“Precultured+Pin,”   the border of the defect, albeit with some fibrillation at the
            n = 4), glued acellular composites (“Acellular+FG,” n = 4),   defect interface.
            or glued precultured composites (“Precultured+FG,” n = 4).                                 2
            Both acellular and cell-laden composites were implanted   Given the size of the created defects (~0.13 cm ), these
            in defects to characterize any potential improvements in   observations are consistent with the short-term repair
                                                                                                2
            resultant repair cartilage due to pMSC preculture and   outcomes seen clinically for defects <4 cm that are treated
                                                                              [41]
            neocartilage formation. Twelve weeks after the initial   with microfracture . However, some pinned and glued
            defect formation and treatment, repair cartilage within   composites also exhibited heterogeneous and incomplete
            defects was evaluated via arthroscopy, gross observation,   defect filling, with more apparent fissures along the defect
            micro-CT, histology, and mechanical testing (Figure 5).  border in defects treated with pinned composites. The
                                                               appearance of repaired cartilage in defects treated with
               Across all the surgeries in which precultured composites   pinned acellular and precultured composites varied. In
            were implanted and explanted, the viability of implants   some instances, damage to the subchondral bone and
            was first investigated via Live/Dead staining of similarly   adjacent cartilage was evident, while in other examples,
            fabricated constructs (same cell and material batch,   repaired tissue adjacent to the pin was opaque and level with
            fabricated at the same time) after the first 7 days of culture   the adjacent tissue . While glued composites resulted in
                                                                              [30]
            in chondrogenic media. Importantly, no differences in cell   similarly heterogeneous repair cartilage, in more instances,
            viability (~79.4% ± 3.0%,  n  = 21) were observed across   glued composites facilitated complete defect filling and the
            precultured composites prepared for separate surgeries. In   formation of smooth cartilage that integrated with the
            addition, the cell viability observed across all these samples   surrounding tissue.
            was consistent with that previously observed in our donor
            screening study (Figure 2C).                          Macroscopic observation of the femoral trochlea
                                                               corroborated the trends observed via arthroscopy.
            3.3. Evaluation of fixation methods and repair     Interestingly, 8 of the 10 defects treated with pinned
            cartilage formation                                composites contained a visible pinhead after explanting
            To characterize the presence of implants and the healing   the femoral trochlea; although it is expected that the pin
            response within cartilage defects 12 weeks after surgery,   would be retained within all defects after 12 weeks based
            nascent repair cartilage was first assessed via arthroscopy   on their previously reported degradation behavior, a 75%
            (Figure 6) [29,40] . Although the appearance of defects and   success rate of implant fixation was also previously reported
            repair cartilage varied across animals, a number of features   with the use of these pins in the same animal model .
                                                                                                           [16]
            were conserved within each of the treatment groups.   Although unlikely, retention of implants within the two
            Within defects that were generally filled, the repair cartilage   defects where the pin could not be readily seen may still
            exhibited a smooth surface and intimate integration along   have been achieved. Given that at least one instance of pin


            Volume 9 Issue 5 (2023)                        500                         https://doi.org/10.18063/ijb.775
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