Mitochondria-Targeted Biophysical Priming of Autologous Biologics for Skin Regeneration and Wound Repair.

Skin aging, photoaging, and chronic wounds are increasingly recognized to be driven by mitochondria-centered mechanisms characterized by oxidative stress, defective mitophagy, and impaired bioenergetics in cutaneous cells. Autologous biologics, including platelet-rich plasma, stromal vascular fraction, bone marrow aspirate concentrate, and mesenchymal stromal/stem cell-derived products, are widely used for skin rejuvenation and wound repair. Recent studies have suggested that many of these effects are mediated by mitochondrial mechanisms, including metabolic reprogramming, redox modulation, and intercellular mitochondrial transfer. Concurrently, biophysical modalities such as red/near-infrared photobiomodulation (PBM), low-intensity pulsed ultrasound, mechanical stimulation, and nanoengineered cues can modulate mitochondrial function in skin-relevant cells. In this review, we integrate these lines of evidence to introduce the concept of mitochondria-targeted biophysical priming of autologous biologics for dermatological applications. We summarize the mitochondrial biology in skin pathology, evaluate these biologics as mitochondria-active therapies, and outline ex vivo priming implementation using PBM, ultrasound, or mechanical stimulation. Finally, we discuss key regulatory considerations that support clinical translation.