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International Journal of Bioprinting                             Implantation of composites for cartilage repair



            the full potential of these scaffolds for cartilage repair.   articular cartilage (i.e., along the femoral trochlea) and
            However, these results suggest that future approaches   possess cartilage with a thickness comparable to human
            for cartilage repair with MEW-reinforced hydrogels   articular cartilage . For example, composite scaffolds
                                                                              [11]
            should be carefully evaluated with regard to their fixation   consisting of woven polycaprolactone (PCL) and either
            approach for construct retention and surrounding   infilled hydrogels (i.e., self-assembling peptide-based
            cartilage tissue damage.                           hydrogels and HA hydrogels) or bone marrow aspirate
                                                               were previously investigated for the treatment of cartilage
                                                               lesions (4 mm diameter) in Yucatan minipigs . Despite
                                                                                                     [9]
            Keywords: Melt electrowriting; Hydrogel; Cartilage   the early observation of scaffold retention in defects
            Repair; Mesenchymal Stromal Cells; Fibrin Glue
                                                               at 6 weeks, defects treated with composites performed
                                                               worse than those treated with microfracture. Similarly,
                                                               biphasic composites of PCL and cell-laden PEG hydrogel
                                                               were evaluated in minipig cartilage defects for 6 months;
            1. Introduction                                    explanted composites resulted in O’Driscoll scores (i.e.,
            A  variety  of  surgical  approaches  have  been  developed   histological scoring) that were worse than empty defect
                                                                                                          [6]
            to treat full-thickness cartilage defects due to trauma   controls, and significant bone resorption was observed .
            and disease, including arthroscopic debridement,      One  significant  challenge  in  implementing  these
            microfracture, and autologous chondrocyte implantation   therapies is the successful fixation and retention of implants
            (ACI) . Importantly, if cartilage defects are left untreated,   within full-thickness cartilage defects [7,12,13] . A range of
                [1]
            they may progress to osteoarthritis (OA), which results   approaches have been investigated for implant fixation ,
                                                                                                           [14]
            in significant pain and joint dysfunction for patients .   including press-fitting, suturing with an overlaying
                                                        [2]
            Unfortunately,  these  approaches fail  to  restore  healthy   periosteal flap, application of fibrin glue/sealant, and the use
            cartilage structure and function, as the repair cartilage   of bone anchors to integrate implants with the underlying
            formed as a result of strategies such as microfracture   bone, among others. While simply press-fitting an implant
            typically exhibits inferior properties when compared to   may be appropriate for osteochondral defects or instances
            healthy articular cartilage . However, the success of each   in which full-thickness cartilage defects are surrounded
                                [3]
            of these respective approaches correlates with defect size,   by healthy, thick cartilage , oftentimes chondral-only
                                                                                     [15]
            which dictates the indication for each procedure . Bone   samples are dislodged from defects due to the complex loads
                                                    [1]
            marrow stimulation via subchondral microfracture is   experienced within the joint [14,16] . Fibrin glue has similarly
            widely considered to be the first option for treating relatively   been combined with press-fitting of implants, but only
            small lesions (<2.5 cm ), with defects ranging between 1   marginally improved the fixation strength and retention
                              2
            and 2.5 cm  responding well to the treatment . However,   of implants [16-18] . Unfortunately, suturing of periosteal
                                                [1]
                     2
            microfracture has previously demonstrated poor patient   flaps to secure implants within defects leads to the loss of
            outcomes in the treatment of larger defects (≥4 cm ) ,    chondrocytes and extracellular matrix (ECM) at the local
                                                       2 [1]
            which typically must be repaired with osteochondral   suture site, as well as the formation of fissures reminiscent of
            allografts where available. For intermediate defect sizes   partial-thickness defects . Bone anchors have been shown
                                                                                  [19]
            (2 cm ), ACI is typically used to mediate repair ; however,   to ensure the retention of implants within defects more
                2
                                                 [1]
            ACI is not usually employed for larger defects (≥4 cm )   reliably , but they often lead to underlying subchondral
                                                         2
                                                                     [9]
            since there is typically a limited number of donor cells that   bone remodeling or voids [18,20] . A recent study evaluated
            can be readily isolated.                           biphasic scaffolds composed of hydroxyapatite and PCL
               In response to the limitations of current approaches   microfiber meshes fabricated via melt electrowriting (MEW)
            for cartilage repair [4,5] , a variety of new tissue engineering   in an equine osteochondral damage model. Six months after
            therapies are being developed, and several have been   implantation, minimal cartilaginous ECM was observed
            evaluated for cartilage repair in large animals [6-9] . These have   in the chondral phase of implants, while micro-computed
            been met with varied success, but highlight the importance   tomography (micro-CT) results showed the collapse of bone
            of selecting models and time points that best recapitulate   anchors used to fix the implants within defects, potentially
                                                                                            [7]
            human cartilage damage in a clinically relevant manner. To   due to improper design and fixation . Generally, both the
            this end, canine, caprine, porcine, and equine models are   cartilage defect size and geometry, as well as the properties
            most commonly used for the investigation of new cartilage   of the implant itself must be considered when selecting the
            repair strategies . Porcine models are often employed   optimal fixation method for scaffolds.
                         [10]
            as large animal models for cartilage damage because   In our previous work, composites of norbornene-
            they  permit easy operative  access to non-load-bearing   modified hyaluronic acid (NorHA) hydrogels mechanically


            Volume 9 Issue 5 (2023)                        494                         https://doi.org/10.18063/ijb.775
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