From a Biodegradable Scaffold to a Living Artery: Native Arterial Wall Regeneration Following Hybrid...

Background Long-term patency of small-diameter vascular grafts remains limited by thrombosis, intimal hyperplasia, and compliance mismatch with native arteries. Despite decades of advances in tissue engineering, no artificial graft has yet been developed that can permanently replicate the multiple biological functions of native vessels, including their antithrombotic properties. We hypothesized that a hybrid tissue-engineered vascular graft composed of endothelial cells (ECs), smooth muscle cells (SMCs), and fibroblasts (FCs) would promote vascular regeneration and facilitate the formation of a native artery-like wall following scaffold degradation. Aim The aim of this study was to evaluate scaffold degradation, vascular wall remodeling, and SMC phenotypic maturation in hybrid tissue-engineered vascular grafts implanted under arterial hemodynamic conditions. Methods Hybrid tissue-engineered vascular grafts were constructed by sequentially seeding autologous ECs, SMCs, and FCs onto a biodegradable lactide/ε-caprolactone scaffold reinforced with bioabsorbable mesh fibers. A total of 12 mongrel dogs were used in this study. Hybrid grafts (5 cm in length) were implanted as carotid artery interposition grafts and harvested after two weeks (n = 4) or eight weeks (n = 4), whereas non-seeded grafts containing extracellular matrix alone served as controls (n = 4). Graft patency, endothelialization, vascular wall organization, scaffold degradation, and SMC phenotype were evaluated by histology, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and morphometric analyses. Results All hybrid grafts remained patent throughout the study period, whereas all control grafts failed within one week after implantation. Complete endothelial coverage was maintained in all patent grafts. Graft diameter increased from 5.0 mm before implantation to 6.0 ± 0.67 mm at two weeks and remained stable thereafter (6.4 ± 0.12 mm at eight weeks). Neoarterial wall thickness increased significantly from 50.8 ± 10.0 μm before implantation to 329 ± 133 μm at two weeks, followed by regression to 99.9 ± 28.4 μm at eight weeks (P < .05). Histological analysis demonstrated progressive organization of vascular wall cells into a layered architecture resembling that of native arteries. Most polymer components were no longer detectable at two weeks and had completely disappeared by eight weeks, whereas reinforcing mesh fibers remained present within the regenerated tissue. TEM demonstrated a temporal transition of SMCs from a synthetic phenotype at two weeks to a predominantly contractile phenotype at eight weeks. Conclusions Hybrid tissue-engineered vascular grafts promoted rapid endothelialization, progressive vascular wall maturation, and complete replacement of the biodegradable scaffold by organized arterial tissue. The transition from synthetic to contractile SMCs, together with the formation of a native artery-like wall despite scaffold degradation, indicates that the graft functioned as a temporary regenerative template rather than a permanent prosthesis. These findings support the feasibility of generating a living arterial conduit capable of long-term remodeling and potentially continued growth following scaffold resorption.