Table 1:

Comparison of models for studying wound repair.

Model	Strengths	Limitations
In vitro monolayer models	• Ease of use • Amenable to genetic manipulation	• Does not reconstitute the complex 3D environment and cell-cell and cell-matrix interactions of the skin. • Fibroblasts undergo pro-fibrotic shift in vitro
Three-dimensional culture systems (spheroid, organotypic, ex vivo)	• Ease of use • Amenable to genetic manipulation and tuning of native-like substrate properties (e.g., stiffness) • In ex vivo culture, contain all relevant cell types in native organization	• Most models do not fully reconstitute all cell-cell and cell-matrix interactions, or functionality, of the skin. • Fibroblasts undergo pro-fibrotic shift in vitro. • May require use of exogenous growth factors or chemical inhibitors in culture media.
Mouse excisional/incisional in vivo wound models	• Ease of use, replicability • Genetically dissectible using transgenic animals • Allows for lineage tracing of fibroblast populations. • Can test potential anti-fibrotic agents.	• Loose skinned animal model with a panniculus carnosus muscle, which is not analogous with human wound healing.
Wound-induced hair neogenesis (WIHN)	• In vivo model of skin regeneration, with recovery of sparse follicles in the scar center.	• No known correlates outside of rodents. • Limited degree of regeneration, with follicles emerging against a scar background.
Mouse xenograft in vivo models	• Ease of use • Provides initial understanding into human wound healing. • Can test potential anti-fibrotic agents.	• Limited insight into immune-fibroblast interactions. • Surgical expertise required to overcome rejection of human skin grafts. • Donor tissue availability for xenografting.
Porcine in vivo models	• Anatomically and physiologically similar to human skin (especially red Duroc pigs)	• Expensive • Transgenic animals are limited • Experimental procedures require surgical and anesthetic expertise.