Table 1.

Comparison of in vitro models for cutaneous wound healing studies.

In Vitro Model Type	Description	Advantages	Disadvantages
Single-cell-type 2D Models	Single-cell types cultured to investigate basic cell signaling responses to injury and stress, typically created by “scratch wounding” techniques.	Simple and cost-effective. Easy to manipulate and control experimental conditions. Provide valuable insights into basic cellular responses to injury.	Lack complexity of tissue microenvironment. Limited representation of cellular interactions and signaling pathways. May not fully replicate in vivo wound healing processes.
Co-culture Systems	Different cell types cultured together to investigate interactions and responses to injury; may be facilitated by Transwell systems for analyzing paracrine factors and/or chemo-tactic responses.	Allow for studying cell–cell interactions. Mimic paracrine signaling between different cell types. Relatively simple to set up and conduct experiments.	May not fully replicate the complex environment of tissue. Limited representation of in vivo wound healing dynamics. Require careful optimization of culture conditions.
3D In Vitro Models	Tissue architecture designed to replicate the physiological complexity of skin tissue, allowing assessment of wound contraction, migration, and matrix compaction in a 3D environment.	Improved simulation of tissue architecture and cellular interactions. Provide a more physiologically relevant environment. Allow for studying cell behavior in a 3D context.	More complex to establish and maintain. Require specialized equipment and expertise. Limited scalability for high-throughput experiments.
3D Skin Equivalents	Advanced models incorporat- ing multiple cell types and lay-ers to mimic native skin architecture, providing insights into tissue regeneration and re-epithelialization.	Closest representation of native skin architecture and function. Allow for studying multiple cell types and their interactions. Can incorporate ECM components for better simulation of tissue microenvironment.	More expensive and time-consuming to develop. Require advanced tissue engineering techniques. May lack full representation of immune response and vasculature.
3D Bioprinting	Constructed patient-specific skin grafts with biomimetic structures.	Enables precise control over tissue architecture and composition. Allows for the creation of patient-specific constructs. Offers potential for person-alized medicine and tissue engineering applications.	Limited by current technology in terms of complexity and scale. Challenges in achieving full functional integration of printed tissues. Costly and requires specialized equipment and materials.
Microfluidic Plat-forms	Microchannel designs to create cell-free wound areas for studying molecular processes in wound healing, including cell migration and interactions.	Provide precise control over microenvironment and cell–cell interactions. Enable real-time imaging and analysis of cellular processes. Offer potential for high-throughput screening and personalized medicine.	Require expertise in microfabrication and microfluidics. Limited representation of tissue architecture and complexity. Challenges in integrating with conventional cell culture techniques.
Ex Vivo Models	Living tissue samples harvested from organisms and cultured to study wound repair mech-anisms.	Close representation of native skin architecture and function maintaining cell–cell interactions. Allow for studying tissue responses in a more physiologically relevant context. Provide valuable insights into wound healing mechanisms.	Limited by tissue availability and viability. Require careful handling and maintenance of tissue samples. Lack dynamic aspects of in vivo wound healing environment.