Promotion of Angiogenesis in Tissue Engineering: Developing Multicellular Matrices with Multiple Capacities

Abstract

One of the aims of tissue engineering is to be able to develop multi-tissue organs in the future. This requires the optimization of conditions for the differentiation of multiple cell types and maintenance of the differentiated phenotype within complex engineered tissues. The goal of this study was to develop prototype tissue engineered matrices to support the simultaneous growth of different cell types with a particular focus on the angiogenic process. We examined two different matrix compositions for the promotion of blood vessel and tube formation. A fibrin-based matrix with the addition of a combination of growth factors supported vascular growth and the invasion of inflammatory cells. Using this fibrin matrix, in combination with a collagen-based hydrogel, a simple in vitro model of the cornea with adjacent sclera was developed that was complete with innervation and vascular structures. In addition, we showed that collagen-based matrices were effective in delivering mononuclear endothelial progenitor cells to ischemic tissue in vivo, and allowing these cells to incorporate into vascular structures. It is anticipated that with further development, these matrices have potential for use as delivery matrices for cell transplantation and for in vitro study purposes of multiple cell types.

The Development of a Tissue-Engineered Cornea: Biomaterials and Culture Methods

“…In a micropig lamellar keratoplasty model, TERP-5 constructs (without supporting or surrounding collagen-CS elements) showed complete reepithelialization within 1 wk, new nerve ingrowth, and epithelial and anterior stromal morphologies (including a regenerated basement membrane) which were comparable to allografts; within 21 d, touch sensitivity had returned to preoperative levels, indicating the restoration of neural function. In an interesting additional application of the TERP material, TERP was blended with fibrinogen, and growth factors to support angiogenesis, and was seeded with isolated DRGs and human umbilical vein endothelial cells (HUVECs), to form a scleral model; this was molded into a ring and the center was filled with a keratocyte-seeded collagen-CS corneal equivalent, with epithelial cells seeded on top (55). In vitro, this appeared to be a good scleral model, as HUVECs led to angiogenesis within the sclera, but the vasculature did not penetrate into the corneal regions; however, nerves originating from the DRGs extended through the sclera and into the corneal stroma and epithelial layers with normal morphologies.…”

Collagen-Based Matrices Improve the Delivery of Transplanted Circulating Progenitor Cells

“…Previous work, including our own, has shown that tissue engineered collagen-based matrices can support multiple tissues and cell types, 12,13 and constitute suitable cell delivery vehicles. [13][14][15] It has been hypothesized that the collagen, which mimics the extracellular matrix, may provide local physical retention and a good platform for cell seeding during direct cell transplantation.…”

“…[13][14][15] It has been hypothesized that the collagen, which mimics the extracellular matrix, may provide local physical retention and a good platform for cell seeding during direct cell transplantation. 14 However, the evaluation of the ability of matrices to improve cell viability and engraftment has so far been limited primarily to histological assessment of tissue at a single time point.…”

Artificial Ovary

“…They have been widely used in the last decade for a variety of tissue engineering applications in adipose [21], cardiovascular [22,23], ocular [24,25], muscle [26,27], liver [28,29], skin [30,31], cartilage [32,33], and bone [34,35] tissues. Moreover, fibrin hydrogels are able to promote angiogenesis [36,37].…”