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Farhat Lab
Farhat Lab

Biomimetric scaffolds

Current tissue engineering technologies involve the use of implantable biodegradable scaffolds which act as a template for tissue regeneration. The rationale behind this approach is that when implanted, the scaffolds have the appropriate environmental cues to trigger the appropriate regenerative response and create functional urinary bladder tissue. However, scaffolds are acellular and they have reduced resistance to urine, a characteristic that make them susceptible to loss of structural integrity secondary to inflammation and fibrosis caused by urine (Farhat 2003, Cartwright, 2005, Brown 2001).
Although host SMC repopulate the matrix, they do not extend throughout the whole graft and thus have provided little contribution to functional reconstruction of the organ. In addition a resulting inflammatory process weakens the scaffolds structural stability to withstand expected physiological and mechanical function and hence may not support the formation of new tissue.

Urological tissue engineering such urinary bladder requires innovative methods to decrease the impact of urine on the healing process. Urine contains many substances such as ammonia, urea, and metabolic waste, all of which may be noxious to tissues and may preclude cellular ingrowth. We have previously demonstrated that bladder ACM is porous and theorize that this porosity in the presence of urine has the potential to play a critical role in graft fibrosis and contracture.

We identified a method to incorporate selective molecules into the ACM in order to decrease porosity and enhance healing process. Hyaluronic Acid (HA) has been recently shown to prevent scar formation after neurolysis in a rabbit model and as an agent for reduction of postoperative adhesions after obstetrical surgeries in humans. Importantly, there is evidence that hyaluronan is helpful in promoting epithelial healing of the bladder and also inhibiting fibrosis when bladder inflammation occurs. In addition, due to its large molecular weight, and heavily hydrated state, it is believed that HA induces complete and rapid hydration of the entire scaffold; allowing growth factors to enter by capillary action and become entrapped in the tortuous pore structure of the scaffold. More importantly, since HA high viscosity allows it to sequester growth factors without altering their activity, thus we are investigating HA to act as a suitable biomimetic material for delivery of different bioactive factors to modulate wound healing and stimulate tissue regeneration in tissue engineering strategies.