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International Journal of Bioprinting                             Implantation of composites for cartilage repair





























            Figure 9. Indentation testing of repair cartilage. Compressive moduli (left), tensile moduli (middle), and permeability (right) of explanted repair cartilage
            quantified via Hertzian biphasic creep testing 12 weeks after composite implantation. n ³ 4, one-way ANOVA with Tukey’s HSD post-hoc test, *p < 0.05,
            **p < 0.01. FG: fibrin glue.


            ensure that all indentation tests were performed on tissues   suggesting delivered and/or endogenous cells mediated
            adjacent and away from pins to avoid any contribution   the elaboration, maturation, and/or remodeling of
            of  the  pin  to  the  mechanical  properties.  Since  the  pins   nascent repair tissue (Figure 9). An additional important
            were also inserted into composites perpendicular to the   consideration is that the 4 mm defect diameter selected in
            cartilage surface, it is unlikely that pins were inadvertently   this model is relatively small (~0.13 cm ) and within the
                                                                                               2
            underlying tested regions of interest. An alternative source   indicated size range that microfracture would be clinically
            for these observed differences in compressive modulus   recommended for a human patient . Therefore, future
                                                                                             [1]
            may be the recruitment of endogenous cells during the   studies with significantly larger defects may be better suited
            formation of pilot holes into the subchondral bone, which   toward illustrating the composites’ potential advantages
            could lead to combinations of composite implantation   in repairing defects that would be otherwise challenging
            with a single microfracture hole.                  to repair (i.e., larger defects approaching or >4 cm ).
                                                                                                            2
                                                               Although fibrin glue appears to be more appropriate for the
               In  accordance  with  the  tension-compression  non-  fixation of MEW-NorHA composites in cartilage defects of
            linearity observed in healthy articular cartilage, the repair   this size, additional studies are required to validate that
            cartilage in all of the experimental groups exhibited tensile   the formation of repair cartilage with glued composites
            moduli that were appreciably larger than their respective   is indeed due to successful retention of implants, and not
            compressive moduli ; however, acellular composites that   the endogenous repair of an empty defect after implant
                            [45]
            were implanted with fibrin glue possessed significantly   translocation. In addition, future studies with longer-term
            higher  tensile  moduli  than pinned acellular composites   time points may better highlight the potential advantages
            and glued precultured composites. Further work would be   of our composite system over traditional approaches for
            needed to understand the reason for this. The permeability   cartilage defect repair in the clinic.
            of repair cartilage across experimental groups is expected
            to have an inverse relationship with the  compressive   Taken together, our arthroscopy, micro-CT, histology,
            and tensile moduli, but this trend was only observed for   and indentation testing demonstrate that further
            the latter, highlighting the variability of the measured   improvements in surgical fixation, overall neocartilage
            mechanical properties.                             properties, and the animal model selected are needed for
                                                               a more thorough assessment of MEW-NorHA composites.
               Despite the variability in healing response observed   Both  PLDLLA  pins  and  fibrin  glue  may  be  used  to  fix
            across all the experimental groups, when comparing   MEW-NorHA composites within full-thickness cartilage
            composites only with their baseline properties prior to   defects, albeit with variable success. While retention of
            implantation (Figure 3), the compressive modulus of   samples with fibrin glue may potentially be less reliable
            implanted composites generally increased over time,   than the use of bioresorbable pins, qualitative reductions


            Volume 9 Issue 5 (2023)                        505                         https://doi.org/10.18063/ijb.775
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