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International Journal of Bioprinting                                   3D-bioprinting of osteochondral plugs




            facilitate the production and maintenance of the cartilage   lesions, has generally good short to mid-term results,
            ECM. 1,4,5  The subchondral bone, which sits directly below   but as the fibrocartilage wears out, pain recurs. 22–25  More
            the calcified cartilage zone, not only anchors the cartilage   recently, cell-based therapies that expand a population
            and distributes mechanical forces, but also provides   of the patient’s cells ex vivo have been developed for the
            much of the nutrient supply needed to maintain healthy   treatment of focal lesions (e.g., matrix-assisted/induced
            cartilage.                                         autologous chondrocyte implantation [MACI]). 26,27
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               Osteoarthritis, the most common form of arthritis,   There  is  conflicting  evidence  on  the  long-term  benefits
            involves the gradual breakdown of hyaline cartilage on the   of MACI when compared to microfracture. Moreover,
            joint surfaces.  More than half of people diagnosed with   MACI and similar cellular grafts and membranes do
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            osteoarthritis are under the age of 65. As there is no cure   not address the subchondral bone, which can lead to
            for osteoarthritis, symptomatic disease progression results   cartilage treatment failure in the absence of a stable base
            in chronic pain and substantially reduced quality of life.   for cartilage repair. Successful treatment of OC injury
            The development of osteoarthritis is linked to, among other   requires the development of a treatment that adequately
            things, aging,  genetics,  and injury.  Cartilage injuries   and simultaneously  regenerates both  the  cartilage and
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            typically result from acute trauma, repeated loading, joint   bone. 28,29  The only current treatment that addresses both
            misalignment, and/or the presence of foreign bodies in the   cartilage and bone regeneration is an OC graft. Autologous
            joint space. Posttraumatic osteoarthritis (PTOA) results   and allogeneic OC grafts replace damaged OC tissue with
            from an acute traumatic joint injury and is a leading cause   donor tissue. Autologous grafts may result in donor site
            of secondary osteoarthritis. 11,12  PTOA can develop from   morbidity and poor healing in arthritis-stricken joints,
            chondral and osteochondral (OC) injuries, as well as   while allogeneic grafts suffer from difficulties in sourcing
            injuries to the meniscus and ligaments that change joint   relatively young and healthy cadaveric tissue and ensuring
            biomechanics.  PTOA is thought to account for more than   viable cell populations. 26,30–33  Moreover, there are size
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            10% of osteoarthritis cases and is an especially important   and shape limitations for both autologous and allogenic
            factor in early-onset osteoarthritis. 11           grafts. 30,34  For advanced  osteoarthritis, joint arthroplasty
                                                               and arthrodesis are the most effective treatments but
               Due to the strenuous physical demands and their
            propensity for  joint  injury,  athletes,  military  service   preclude participation in many activities and result in
                                                               substantially reduced mobility and chronic pain. Therefore,
            members, and members of professions that require
            physical  conditioning  and  activity  suffer  higher  rates  of   an innovative approach that addresses both cartilage and
            osteoarthritis than the general population. 14–18  Combat   bone regeneration is required to effectively treat chondral
            injuries involving traumatic injury to the knee or ankle   and OC injuries with long-term efficacy, ensuring a high
            result in the development of osteoarthritis in more than   quality of life.
            90% of cases.  Hence, new treatments are needed to prevent   3D printing technologies offer promise for addressing
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            the onset of osteoarthritis by addressing traumatic joint   OC injuries with improved long-term outcomes. 3D
            injuries effectively. OC injuries present distinct challenges   printing, in which structures are fabricated based on digital
            due to the poor regenerative capacity of cartilage, which   models, offers distinct advantages for the fabrication of tissue
            usually does not fully heal.  Chondrocytes in mature and   scaffolds that aim to recapitulate the complexity of native
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            healthy cartilage do not proliferate or do so very slowly. OC   tissue. 35,36  The field of tissue engineering (TE), which aims
            injuries that extend to the subchondral bone can recruit   to mimic the complexity of native tissue via a combination
            cells from the vascularized subchondral bone to induce   of cells, scaffolds, and biochemical or biomechanical
            a healing response, but the damaged tissue is replaced by   stimuli, reaps substantial benefits from the use of 3D
            fibrocartilaginous tissue rather than hyaline cartilage. 20,21    printing.  For example, 3D printing of TE constructs, or 3D
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            The inferior wear properties of fibrocartilage compared to   bioprinting, can be used to create structures with material,
            hyaline cartilage result in cartilage erosion and, in many   stiffness, porosity, and cell density gradients similar
            cases, lead to the development of osteoarthritis.    to native OC tissue.  Unlike many traditional scaffold
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               Surgical and non-surgical techniques have been   fabrication techniques, bioprinting can readily incorporate
            developed in an attempt to repair cartilage and abate   multiple materials and embed live human cells and growth
            osteoarthritis  progression.  As  mentioned,  there  factors into scaffolds during printing. 35,37,39  Prior work has
            unfortunately is no cure for osteoarthritis, and the   demonstrated the bioprinting of relatively simple thin disks
            articular surface continues to degenerate with age. Non-  of a single material for chondral TE to complex biomimetic
            surgical treatments focus on temporary symptomatic relief   multiphasic structures of OC tissue. 40,41  A range of natural
            but  fail  to  halt  disease  progression.  Minimally  invasive   and synthetic materials have been bioprinted for OC TE,
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            microfracture, which is widely used to treat small chondral   including alginate,  agarose,  collagen,  gelatin,  HA,
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            Volume 10 Issue 4 (2024)                       533                                doi: 10.36922/ijb.4053
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