The human joint as a discrete organ is composed of multiple connective tissues including cartilage, bone, tendon, ligament, and muscle. Trauma or degeneration of any component of these tissues is a common cause of joint dysfunction and often results in restricted function, possibly requiring joint surgery over time. Recent evidence suggests that one in two adult Americans live with a joint-related condition – the same number as those with cardiovascular or chronic respiratory diseases combined.

In orthopaedics, the demand for novel minimally invasive therapies is driven by a lack of effective treatments for common connective tissue degenerative diseases such as osteoarthritis. Several sources of stem and progenitor cells, able to self-renew and differentiate towards multiple musculoskeletal lineages, have been identified and investigated as therapeutic vehicles. Lately, stem cell therapies are emerging as potentially effective treatments for joint-relevant connective tissue conditions toward the goal of joint preservation. However, data supporting such stem cell based therapies is severely limited due to lack of rigour in clinical studies and suboptimal reporting of postoperative complications. Moreover, other concerns such as genetic instability, spontaneous transformation, and carcinogenicity have also been raised for specific expansion protocols. Therefore, further understanding of the biological performance of stem cells as orthobiologics is mandatory. High-quality evidence from all stakeholders involved in stem cell therapy research and clinical practice is necessary to refine the role of stem cells for successful joint preservation.

This Special Issue therefore invites multidisciplinary contributions from original research articles focusing on recent progress on mechanistic understanding and enhancement of existing and potential stem cell therapies for connective tissue regeneration. Review articles that describe the current state of the art are also welcomed.

Potential topics include but are not limited to the following:

• In vitro, ex vivo, and translational studies of stem cell therapies for connective tissue regeneration
• Clinical trials of stem cell therapies for post-injury connective tissue regeneration
• Studies of the developmental mechanisms of osteogenesis
• Studies of the developmental mechanisms of chondrogenesis and tenogenesis
• Novel investigations based on additive manufacturing, machine learning, and artificial intelligence, genomics, and bioinformatics