Regenerative Rehabilitation and Tissue Reconstruction: Biological Mechanisms Driving Functional Recovery

Dear Colleagues,

Regenerative rehabilitation is an emerging interdisciplinary field that integrates principles of regenerative medicine and rehabilitation science to promote tissue repair and restore function after injury or disease. By combining biological approaches, such as stem cell therapies, tissue engineering and bioactive factors, with targeted rehabilitation interventions including mechanical loading, exercise and neuromodulation, this field aims to enhance both structural regeneration and functional recovery. In neurological disorders, regenerative rehabilitation is increasingly recognized as a transformative paradigm to support neural repair and recovery processes.

Growing evidence suggests that rehabilitation is not merely supportive but acts as an active biological modulator of tissue regeneration. Mechanical and electrical stimuli can influence stem cell differentiation, extracellular matrix remodeling and neuroplastic processes, promoting synaptogenesis, axonal sprouting and functional integration of newly formed tissues.

Mechanotransduction plays a central role in this framework. Mechanical cues generated by rehabilitation interventions are converted into biochemical signals that regulate gene expression, cytoskeletal organization and cell fate, thereby directly influencing tissue repair and neural reorganization. In parallel, extracellular matrix remodeling provides both structural support and biochemical signaling essential for axonal guidance, synaptic stabilization and cellular integration, representing a key interface between regenerative processes and functional outcomes.

In neurological conditions such as stroke and acquired brain injury, movement-based rehabilitation can modulate neurotrophic signaling and enhance neuroplasticity, facilitating circuit reorganization and improving functional outcomes.

This Special Issue aims to investigate the biological mechanisms and clinical applications underlying tissue reconstruction within rehabilitation medicine, with a particular focus on how rehabilitation-driven stimuli shape regenerative processes. Emphasis will be placed on mechanotransduction, extracellular matrix remodeling and neuroplasticity as interconnected drivers of functional recovery, as well as on the integration of regenerative therapies into clinical rehabilitation pathways.

Topics of interest include, but are not limited to: neuroplasticity and regeneration, stem cell-based therapies, mechanotransduction, extracellular matrix remodeling, neuromodulation and multidisciplinary translational approaches.

Dr. Stefano Bonomi
Dr. Augusto Fusco
Guest Editors

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