Stem cell-based therapies to promote skeletal regeneration have been the focus of intensive efforts in the past decades. While important progress has been made, substantial challenges remain in the field regarding the identity and function as well as the clinical translation of stem cells. The molecular and epigenetic control of stem cell states and dynamic interactions between stem cells and the tissue microenvironment have been fundamental questions, whose answers are underpinnings for efficient clinical applications. Therapeutically, several key approaches have emerged recently, including transplantation of in vitro cultured stem cells or reconstituted tissues, as well as homing and reprogramming of native stem cells. Although skeletal regeneration mediated by exogenous stem cells have been promising, the approach is confined by limitations including insufficient homing of stem cells to repair site, low efficiency of stem cell engraftment, and reduced differentiation of stem cells in vivo. To overcome these challenges, many strategies have been developed to enhance transplanted stem cell homing, engraftment, and differentiation. Alternatively, exciting strategies have been developed to target endogenous stem cells to reprogram their lineage commitment and improve their regeneration potentials.

To highlight the tremendous advances taking place in the field, this special issue aims to discuss new strategies for circumventing the hurdles in skeletal regeneration by exploiting exogenous and endogenous stem cells. Therefore, we welcome original research articles as well as review articles.

Potential topics include but are not limited to the following:

• Identification and characterization of novel stem/progenitor cell populations in skeletal tissues
• Molecular and epigenetic mechanisms governing skeletal stem cell self-renewal and differentiation
• Dynamic interactions between stem/progenitor cells with tissue niche and microenvironment
• Novel growth factors, small molecules, or antibodies targeting native/endogenous stem cells for treatment of skeletal disorders
• Novel approaches to enhance cells homing of stem/progenitor cells to the injured site and promote skeleton regeneration
• Novel biomaterial/scaffolds that enhance skeletal tissue repair and regeneration