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Abstract Recapitulation of multiscale structure–function properties of cells, cell‐secreted extracellular matrix, and 3D architecture of natural tissues is central to engineering biomimetic tissue substitutes. Toward achieving biomimicry, a variety of biofabrication processes have been developed, which can be broadly classified into five categories—fiber and fabric formation, additive manufacturing, surface modification, remote fields, and other notable processes—each with specific advantages and limitations. The majority of biofabrication literature has focused on using a single process at a time, which often limits the range of tissues that could be created with relevant features that span nano to macro scales. With multiscale biomimicry as the goal, development of hybrid biofabrication strategies that synergistically unite two or more processes to complement each other's strengths and limitations has been steadily increasing. This work discusses recent literature in this domain and attempts to equip the reader with the understanding of selecting appropriate processes that can harmonize toward creating engineered tissues with appropriate multiscale structure–function properties. Opportunities related to various hybridization schemes and a future outlook on scale‐up biofabrication have also been discussed. This article is categorized under:Nanotechnology Approaches to Biology > Nanoscale Systems in BiologyImplantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement 

Abstract There is a need for the development of effective treatments for focal articular cartilage injuries. We previously developed a multiphasic 3D‐bioplotted osteochondral scaffold design that can drive site‐specific tissue formation when seeded with adipose‐derived stem cells (ASC). The objective of this study was to evaluate this scaffold in a large animal model. Osteochondral defects were generated in the trochlear groove of Yucatan minipigs and repaired with scaffolds that either contained or lacked an electrospun tidemark and were either unseeded or seeded with ASC. Implants were monitored via computed tomography (CT) over the course of 4 months of in vivo implantation and compared to both open lesions and autologous explants. ICRS II evaluation indicated that defects with ASC‐seeded scaffolds had healing that most closely resembled the aulogous explant. Scaffold‐facilitated subchondral bone repair mimicked the structure of native bone tissue, but cartilage matrix staining was not apparent within the scaffold. The open lesions had the highest volumetric infill detected using CT analysis (p < 0.05), but the repair tissue was largely disorganized. The acellular scaffold without a tidemark had significantly more volumetric filling than either the acellular or ASC seeded groups containing a tidemark (p < 0.05), suggesting that the tidemark limited cell infiltration into the cartilage portion of the scaffold. Overall, scaffold groups repaired the defect more successfully than an open lesion but achieved limited repair in the cartilage region. With further optimization, this approach holds potential to treat focal cartilage lesions in a highly personalized manner using a human patient's own ASC cells.