Handheld Bioprinters in Skin Regeneration: Current Landscape, Clinical Promise, and the Road Ahead

Portable handheld bioprinters represent a transformative advancement in personalized skin regeneration, bypassing the logistical constraints of stationary lab-based systems by enabling real-time, in situ fabrication of bioengineered constructs directly within the wound bed. This review aims to evaluate the current state of their development and clinical translation. One of the foci is placed on the stringent physicochemical requirements for bioinks, where we examined the critical balance between bioadhesion-facilitated by functional groups-and mechanical cohesion necessary for maintaining structural integrity during deposition, while RGD motifs are considered primarily as promoters of integrin-mediated cell adhesion. Preclinical studies have demonstrated promising effects of bioprinted constructs on wound healing and tissue organization; however, human evidence for handheld and direct in situ skin bioprinting remains limited, and clinical efficacy has yet to be established in controlled studies. Nevertheless, widespread adoption is hindered by inferior printing fidelity relative to stationary counterparts, a lack of standardized GMP-compliant bioink production, and regulatory ambiguity that impedes clear classification as either medical devices or biologics. Practical barriers, including intraoperative sterility assurance and operator training, also remain unresolved. Looking ahead, we discuss how the convergence of, in particular, artificial intelligence for real-time wound morphometry, closed-loop process control, and smart, self-healing biomaterials promises to surmount these obstacles. We conclude that these synergistic innovations may propel handheld bioprinters from experimental prototypes toward clinical tools with the potential to reshape reconstructive surgery and emergency wound care, although their clinical value will require validation in appropriately designed human studies.