In-situ bioprinting at bioactive wound interfaces: A clinically driven design-rule framework

Chronic and complex wounds exist within heterogeneous, unstable clinical environments characterized by irregular geometry, persistent exudate, bleeding, and strict time constraints at the bedside. Despite advances in biomaterials, skin substitutes, and bioprinting technologies, most wound-healing strategies are still developed and validated under controlled laboratory conditions that fail to capture these realities, contributing to limited clinical translation. In-situ bioprinting reframes wound treatment as an on-site biofabrication problem, enabling the direct deposition of bioactive constructs onto living tissue at the point-of-care. However, current literature remains largely material- and technology-centered, with no unified framework that links real wound constraints to printable design parameters. In this mini-review, we establish a clinically driven design-rule framework that systematically maps on-wound constraints to key printable parameters, including gelation kinetics, viscosity windows, spatial patterning, and degradation behavior. By synthesizing recent experimental and translational studies, we map these parameters to clinically relevant outcomes such as rapid hemostasis, infection control, angiogenesis, and long-term tissue remodeling. We further identify wound-edge heterogeneity as one important but underappreciated constraint among several interacting factors that shape design requirements and outline translational and regulatory challenges unique to point-of-care biofabrication. By shifting the focus from material composition to constraint-driven design logic, this work provides a practical framework for developing clinically robust in-situ bioprinting strategies.