“Smart” Autologous Tissue Engineering for Soft Tissue Reconstruction

Tissue engineering and gene transfer of recombinant DNA of choice represent two fascinating technologies with intriguing promises in tissue reconstruction. The ultimate tissue engineering construct for tissue repair should be autologous to optimally integrate without rejection, three-dimensional to bridge deep defects, porous to allow cell migration, bio-inductive for cells to proliferate and to produce topically extra cellular matrix components, bio-inductive for vascular sprouts to develop within from (progenitor) cells, and chemotactic for cells from the wound surroundings to infiltrate and stimulate vasculogenesis to optimize tissue integration.

So far, tissue engineering and gene therapy protocols for tissue repair have been focusing on validation principally in studies in rats and mice. These lower mammals do not represent a human tissue repair model in terms of tissue integration, vascularization, and immunologic processes. The relevant concepts must be further investigated in larger mammalian models which ideally mimic human tissue regeneration and reconstruction.

The authors use ex vivo gene transfer protocols in a standardized porcine wet wound healing model to create “smart constructs.” They have cultivated porcine autologous basal stem cell keratinocytes transfected with recombinant DNA of Vasculo Endothelial Growth Factor and Epidermal Growth Factor in supplement to autologous fibroblasts. These transgene cell cultures are seeded into autologous porcine polymerized gels to obtain a 3-D tissue construct. Endothelial Progenitor stem cell tracers were inserted within the construct to promote arteriogenesis and angiogenesis which, in a later phase, enable microvascular connection with blood vessels in the defect environment.

Regulation of the growth factor expression from integrated transgene cells within the construct is realized with a tetracycline-inducible genetic switch, inserted by ex vivo liposome mediated gene transfer into the applied growth factor plasmid. This allows the authors to induce, tune, or finalize growth factor over-expression in vivo in the defect.

Smart autologous tissue engineering for tissue repair has great promises for tissue reconstruction. Microsurgical techniques will allow for tissue integration of the engineered construct into the defect.