In VivoRemodeling of Fibroblast-Derived Vascular Scaffolds Implanted for 6 Months in Rats

Abstract

There is a clinical need for tissue-engineered small-diameter (<6 mm) vascular grafts since clinical applications are halted by the limited suitability of autologous or synthetic grafts. This study uses the self-assembly approach to produce a fibroblast-derived decellularized vascular scaffold (FDVS) that can be available off-the-shelf. Briefly, extracellular matrix scaffolds were produced using human dermal fibroblasts sheets rolled around a mandrel, maintained in culture to allow for the formation of cohesive and three-dimensional tubular constructs, and decellularized by immersion in deionized water. The FDVSs were implanted as an aortic interpositional graft in six Sprague-Dawley rats for 6 months. Five out of the six implants were still patent 6 months after the surgery. Histological analysis showed the infiltration of cells on both abluminal and luminal sides, and immunofluorescence analysis suggested the formation of neomedia comprised of smooth muscle cells and lined underneath with an endothelium. Furthermore, to verify the feasibility of producing tissue-engineered blood vessels of clinically relevant length and diameter, scaffolds with a 4.6 mm inner diameter and 17 cm in length were fabricated with success and stored for an extended period of time, while maintaining suitable properties following the storage period. This novel demonstration of the potential of the FDVS could accelerate the clinical availability of tissue-engineered blood vessels and warrants further preclinical studies.

Regenerative immunology: the immunological reaction to biomaterials

“…Both neutrophilic and giant cell infiltrations have been seen after implantation of porcine and human scaffolds into rats . Mononuclear cells invade the peri‐implant space as early as at 24 h of implantation, and this process can continue for several months leading to chronic inflammation and encapsulation or scar formation . On the other hand, when circulating monocytes are absent, normal remodeling of the ECM scaffold does not occur, implying that mononuclear cells play an important role in the constructive remodeling process .…”

In Vivo Performance of Decellularized Vascular Grafts: A Review Article

“…The engineered vessels were then decellularized, re-seeded with cells and were implanted in vivo. The results showed less neointimal hyperplasia, but increased neo-endothelialization, smooth muscle repopulation, and tissue regeneration of vascular grafts in vivo [ 20 , 28 , 119 , 142 , 147 ]. Another novel technique that has been applied to decellularized vascular grafts results in “hybrid” vascular grafts.…”

Immune responses towards bioengineered tissues and strategies to control them

“…encapsulation, or scar formation [21]. Mononuclear cells are also fundamental for tissue regeneration [22]; without these, normal remodeling of the ECM scaffold does not occur [23].…”