Treatment of musculoskeletal injuries and diseases has been advanced over the past decades with the development of stem cell and tissue engineering approaches in regenerative medicine. Directional differentiation of stem cells into specific lineages to form bone, cartilage, tendon, ligament, muscle, and meniscus has shown promise in musculoskeletal tissue engineering. Approaches including the utilisation of biomaterials, biochemical signals, and mechanical stimuli, alone or in combination, to create a conductive microenvironment to stem cell differentiation and tissue regeneration, have been studied and have been shown to have significant clinical relevance.

To identify the microenvironmental signals that can direct stem cell differentiation, it is necessary to understand the mechanisms of tissue development and the healing process, and to identify key regulators. The physical, chemical, biological, and mechanical properties of biomaterials can be optimised to guide material-induced cell responses. The precise spatiotemporal presentation of inducing signals and the combinatorial application of multiple signals can maximise the effect on stem cell differentiation.

This Special Issue aims to exhibit recent advances in the directional differentiation of stem cells for musculoskeletal tissue regeneration. Original research articles, review articles, and clinical studies on stem cell and tissue engineering related to musculoskeletal systems are most welcome in this Special Issue.

Potential topics include but are not limited to the following:

• Recent advances in directing stem cell differentiation into specific lineages
• Identification of novel biochemical signals for directional differentiation of stem cells
• Biomaterial design and application for lineage-specific differentiation of stem cells
• Mechanical stimuli applied for directional differentiation of stem cells
• Molecular mechanisms of inducing signals during stem cell differentiation
• Applications of stem cell therapy for musculoskeletal tissue regeneration
• Applications of tissue-engineered scaffold for musculoskeletal tissue regeneration