Neutrophils play a pivotal role in orchestrating the immune system response to biomaterials, the onset and resolution of chronic inflammation, and macrophage polarization. However, the neutrophil response to biomaterials and the consequent impact on tissue engineering approaches is still scarcely understood. Here, we report an in vitro culture model that comprehensively describes the most important neutrophil functions in the light of tissue repair. We isolated human primary neutrophils from peripheral blood and exposed them to a panel of hard, soft, naturally- and synthetically-derived materials. The overall trend showed increased neutrophil survival on naturally derived constructs, together with higher oxidative burst, decreased myeloperoxidase and neutrophil elastase and decreased cytokine secretion compared to neutrophils on synthetic materials. The culture model is a step to better understand the immune modulation elicited by biomaterials. Further studies are needed to correlate the neutrophil response to tissue healing and to elucidate the mechanism triggering the cell response and their consequences in determining inflammation onset and resolution.

Articular cartilage (AC) is an avascular and flexible connective tissue located on the bone surface in the diarthrodial joints. AC defects are common in the knees of young and physically active individuals. Because of the lack of suitable tissue-engineered artificial matrices, current therapies for AC defects, especially full-thickness AC defects and osteochondral interfaces, fail to replace or regenerate damaged cartilage adequately. With rapid research and development advancements in AC tissue engineering (ACTE), functionalized hydrogels have emerged as promising cartilage matrix substitutes because of their favorable biomechanical properties, water content, swelling ability, cytocompatibility, biodegradability, and lubricating behaviors. They can be rationally designed and conveniently tuned to simulate the extracellular matrix of cartilage. This article briefly introduces the composition, structure, and function of AC and its defects, followed by a comprehensive review of the exquisite (bio)design and (bio)fabrication of functionalized hydrogels for AC repair. Finally, we summarize the challenges encountered in functionalized hydrogel-based strategies for ACTE both in vivo and in vitro and the future directions for clinical translation.

Clinical treatments for the repair of osteochondral defects (OCD) are merely palliative, not completely curative, and thus enormously unfulfilled challenges. With the in-depth studies of biology, medicine, materials, and engineering technology, the conception of OCD repair and regeneration should be renewed. During the past decades, many innovative tissue-engineered approaches for repairing and regenerating damaged osteochondral units have been widely explored. Various scaffold-free and scaffold-based strategies, such as monophasic, biphasic, and currently fabricated multiphasic and gradient architectures have been proposed and evaluated. Meanwhile, progenitor cells and tissue-specific cells have also been intensively investigated in vivo as well as ex vivo. Concerning bioactive factors and drugs, they have been combined with scaffolds and/or living cells, and even released in a spatiotemporally controlled manner. Although tremendous progress has been achieved, further research and development (R&D) is needed to convert preclinical outcomes into clinical applications. Here, the osteochondral unit structure, its defect classifications, and diagnosis are summarized. Commonly used clinical reparative techniques, tissue-engineered strategies, emerging 3D-bioprinting technologies, and the status of their clinical applications are discussed. Existing challenges to translation are also discussed and potential solutions for future R&D directions are proposed.