Approaches to improve angiogenesis in tissue‐engineered skin

Abstract

A problem with tissue-engineered skin is clinical failure due to delays in vascularization. The aim of this study was to explore a number of simple strategies to improve angiogenesis/vascularization using a tissue-engineered model of skin to which small vessel human dermal microvascular endothelial cells were added. For the majority of these studies, a modified Guirguis chamber was used, which allowed the investigation of several variables within the same experiment using the same human dermis; cell type, angiogenic growth factors, the influence of keratinocytes and fibroblasts, mechanical penetration of the human dermis, the site of endothelial cell addition, and the influence of hypoxia were all examined. A qualitative scoring system was used to assess the impact of these factors on the penetration of endothelial cells throughout the dermis. Similar results were achieved using freshly isolated small vessel human dermal microvascular endothelial cells or an endothelial cell line and a minimum cell seeding density was identified. Cell penetration was not influenced by the addition of angiogenic growth factors (vascular endothelial growth factor and basic fibroblast growth factor); similarly, including epidermal keratinocytes or dermal fibroblasts did not encourage endothelial cell entry, and neither did mechanical introduction of holes throughout the dermis. Two factors were identified that significantly enhanced endothelial cell penetration into the dermis: hypoxia and the site of endothelial cell addition. Endothelial cells added from the papillary surface entered into the dermis much more effectively than when cells were added to the reticular surface of the dermis. We conclude that this model is valuable in improving our understanding of how to enhance vascularization of tissue-engineered grafts.

Prevascularization of a Fibrin-Based Tissue Construct Accelerates the Formation of Functional Anastomosis with Host Vasculature

“…4,5 This method does not depend on an autologous cell source, but the slow growth of new vessels may compromise tissue viability. 6 Alternatively, one can seed vascular endothelial cells into the implanted tissue as a means of accelerating vessel formation. [7][8][9][10][11] This method relies on vasculogenesis in situ, and the time it takes for this process to occur may, again, compromise the implanted tissue.…”

Accelerated angiogenesis by continuous medium flow with vascular endothelial growth factor inside tissue-engineered trachea☆

“…These results have highlighted the importance of the reepithelialization process to achieve a functional trachea substitute [3][4][5]. The experience gained from tissue-engineered skin demonstrated that epithelial cells have better survival chances on a well-vascularized wound surface [6,7], a clear proof that revascularization is the essence of reepithelialization.…”

Tissue-engineered trachea: History, problems and the future☆

“…These results were not surprising at all, since the entire history of trachea replacement has highlighted the importance of a complete reepithelialization process in building a functional tracheal substitute. The experience gained from tissueengineered skin demonstrated that epithelial cells have better survival chances on a well vascularized wound surface, a clear proof that revascularization is the essence of reepithelialization [41][42][43][44].…”