Bioprinting offers tremendous potential in the fabrication of functional tissue constructs for replacement of damaged or diseased tissues. Among other fabrication methods used in tissue engineering, bioprinting provides accurate control over the construct's geometric and compositional attributes using an automated approach. Bioinks are composed of the hydrogel material and living cells that are critical process variables in the fabrication of functional, mechanically robust constructs. Appropriate cells can be encapsulated in bioinks to create functional tissue structures. Ideal bioinks are required to undergo a sol–gel transition consuming minimal processing time, and a plethora of chemical and physical crosslinking mechanisms are generally exploited to achieve high shape fidelity and construct stability. In contrast, crosslinking of hydrogel material at rapid rates can cause nozzle clogging, and hence, optimization of the bioink is often necessary. Bioinks can be formulated using natural or synthetic biomaterials, alone or in combination of these biomaterials. Herein, the various bioprinting methods are discussed; the natural, synthetic, or hybrid materials used as bioinks are analyzed; and the challenges, limitations, and future directions concerning the bioprinting technique are appraised.

Advanced biomaterial‐guided delivery of gene vectors is an emerging and highly attractive therapeutic solution for targeted articular cartilage repair, allowing for a controlled and minimally invasive delivery of gene vectors in a spatiotemporally precise manner, reducing intra‐articular vector spread and possible loss of the therapeutic gene product. As far as it is known, the very first successful in vivo application of such a biomaterial‐guided delivery of a potent gene vector in an orthotopic large animal model of cartilage damage is reported here. In detail, an injectable and thermosensitive hydrogel based on poly(ethylene oxide) (PEO)–poly(propylene oxide) (PPO)–PEO poloxamers, capable of controlled release of a therapeutic recombinant adeno‐associated virus (rAAV) vector overexpressing the chondrogenic sox9 transcription factor in full‐thickness chondral defects, is applied in a clinically relevant minipig model in vivo. These comprehensive analyses of the entire osteochondral unit with multiple standardized evaluation methods indicate that rAAV‐FLAG‐hsox9/PEO–PPO–PEO hydrogel‐augmented microfracture significantly improves cartilage repair with a collagen fiber orientation more similar to the normal cartilage and protects the subchondral bone plate from early bone loss.

Therapeutic gene transfer into articular cartilage is a potential means to stimulate reparative activities in tissue lesions. We previously demonstrated that direct application of recombinant adeno-associated virus (rAAV) vectors to articular chondrocytes in their native matrix in situ as well as sites of tissue damage allowed for efficient and sustained reporter gene expression. Here we test the hypothesis that rAAV-mediated overexpression of fibroblast growth factor 2 (FGF-2), one candidate for enhancing the repair of cartilage lesions, would lead to the production of a biologically active factor that would facilitate the healing of articular cartilage defects. In vitro, FGF-2 production from an rAAV-delivered transgene was sufficient to stimulate chondrocyte proliferation over a prolonged period of time. In vivo, application of the therapeutic vector significantly improved the overall repair, filling, architecture, and cell morphology of osteochondral defects in rabbit knee joints. Differences in matrix synthesis were also observed, although not to the point of statistical significance. This process may further benefit from cosupplementation with other factors. These results provide a basis for rAAV application to sites of articular cartilage damage to deliver agents that promote tissue repair.

Objective: Human osteoarthritis (OA) is characterized by a pathologic shift in articular cartilage homeostasis toward the progressive loss of extracellular matrix (ECM). The purpose of this study was to investigate the ability of rAAV‐mediated SOX9 overexpression to restore major ECM components in human OA articular cartilage.Methods: We monitored the synthesis and content of proteoglycans and type II collagen in 3‐dimensional cultures of human normal and OA articular chondrocytes and in explant cultures of human normal and OA articular cartilage following direct application of a recombinant adeno‐associated virus (rAAV) SOX9 vector in vitro and in situ. We also analyzed the effects of this treatment on cell proliferation in these systems.Results: Following SOX9 gene transfer, expression levels of proteoglycans and type II collagen increased over time in normal and OA articular chondrocytes in vitro. In situ, overexpression of SOX9 in normal and OA articular cartilage stimulated proteoglycan and type II collagen synthesis in a dose‐dependent manner. These effects were not associated with changes in chondrocyte proliferation. Notably, expression of the 2 principal matrix components could be restored in OA articular cartilage to levels similar to those in normal cartilage.Conclusion: These data support the concept of using direct, rAAV‐mediated transfer of chondrogenic genes to articular cartilage for the treatment of OA in humans.