Overview of Advanced in vitro and ex vivo Test Methods for Preclinical Evaluation of Wound Care Products

BACKGROUND: This review summarizes published literature on in vitro and ex vivo test methods for preclinical evaluation of wound care products. There is currently no guidance from, e.g., authorities on how wound care products, especially antimicrobial wound care products, should be assessed regarding their cell toxic effects and their antimicrobial performance. Even though ISO 10993-1 gives clear guidance for biocompatibility evaluation of medical devices, the corresponding methods do not reflect wound conditions. Regarding antimicrobial efficacy, the first standard EN 17854 for wound dressings was published recently. For all other endpoints, no standards are available. In addition, there are increased ethical considerations that animal testing should be avoided. This was first practiced in cosmetic industry and is now implemented presenting a central part of ISO 10993-1 for toxicity assessment of medical devices. At the same time, there is increasing evidence that in vitro and ex vivo methods can replace animal testing for certain endpoints with the advantage that a partially difficult transfer of data from animals to humans may not be needed anymore. This review presents a comprehensive overview of methods that can be used for preclinical evaluation of wound care products. SUMMARY: In three tables, a new matrix for testing biocompatibility, healing, and antimicrobial endpoints for wound dressings, semi-liquid wound care products, as well as liquid products are presented. This matrix should give guidance to manufacturers during development and regulatory approval processes. Some of the methods, e.g., 3D wound models, may answer clinical questions in vitro, which are difficult to answer in a clinical study due to various reasons. KEY MESSAGES: We conclude that a broad range of in vitro and ex vivo methods are available and can be employed supporting development and regulatory approval of innovative wound care products ranging from dressing to semi-liquid and liquid products while at the same time reduce animal testing.