Emerging Strategies for Bioprinting Organized Musculoskeletal Tissues with Biomimetic Collagen Architecture

Collagen fiber organization is critical to the biomechanical function of musculoskeletal tissues. This has motivated increased interest in tissue engineering strategies aiming to recapitulate native collagen architecture in order to generate more biomimetic grafts. In particular, three-dimensional (3D) bioprinting has emerged as a powerful biofabrication platform capable of generating patient-specific constructs containing cells, supporting biomaterials, and diverse regulatory factors (e.g., genes, proteins, and small molecules). This paper will review how emerging bioprinting strategies can also be used to provide spatially defined external and/or internal biophysical cues to cells, thereby modulating their phenotype and the organization of the extracellular matrix they produce in culture. Furthermore, we will explore how postbioprinting interventions such as temporal enzymatic treatments and mechanical stimulation can be used to further promote cell and collagen alignment, matrix remodeling, and tissue maturation. Together, these approaches hold significant promise for the development of next-generation grafts for the treatment of diverse musculoskeletal injuries.