The effect of mechanical tension on bolus morphology and integration following intradermal injection in an ex vivo human skin model

Intradermal (ID) injection is an increasingly utilized route of administration for both therapeutic and aesthetic dermatology applications. Preclinical evaluation of both delivery and efficacy is an essential step in the development pipeline. Conducting these studies in a system that recapitulates the target tissue structure and biological response is essential for accurate prediction of clinical efficacy. The use of ex vivo human skin tissue is the gold standard for these studies and offers an ideal platform for this evaluation. However, mechanical tension, an important aspect of in vivo skin homeostasis, is generally absent in these models, which can have a significant influence on dermal fiber alignment, tissue integrity, and bolus morphology. Here, we compare these aspects of injection delivery in explant human skin cultured in a traditional manner, i.e., in a relaxed state, to explant skin cultured at a physiologically relevant tension (TenSkin™). Hyaluronic acid-based dermal fillers were utilized as tool formulations, which enabled bolus visualization through Alican blue staining. Histological examination and automated image segmentation (MATLAB R2002b) revealed tissue cultured in a relaxed state exhibited an artificial thickening of the dermal layer leading to a decrease in dermal fiber alignment. While bolus cross-sectional areas were equivalent in both the relaxed and tensioned tissue, bolus morphology was significantly less spherical in tensioned tissue, leading to a higher degree of dermal integration. Over time in culture (1-2 weeks), gross degradation in tissue integrity was also observed in the relaxed tissue compared to tensioned tissue in the TenSkin™ model. These results highlight the importance normal physiological mechanical forces can play in tissue responses to widely used interventions.