In vivo regeneration of small‐diameter (2 mm) arteries using a polymer scaffold

Abstract

The difficulty of obtaining significant long-term patency and good wall mechanical strength in vivo has been a significant obstacle in achieving small-diameter vascular prostheses. The aim of the present study was to develop a prosthetic graft that could perform as a small-diameter vascular conduit. Tubular structures of hyaluronan (HYAFF-11 tubules, 2 mm diameter, 1 cm length) were grafted in the abdominal aorta of 30 rats as temporary absorbable guides to promote regeneration of vascular structures. Performance was assessed by histology, immunohistochemistry, and ultra-structural analysis. These experiments resulted in three novel findings: 1) complete endothelialization of the tube's luminal surface occurred; 2) sequential regeneration of vascular components led to complete vascular wall regeneration 15 days after surgery; and 3) the biomaterial used created the ideal environment for the delicate regeneration process during the critical initial phases, yet its biodegradability allowed for complete degradation of the construct four months after implantation, at which time, a new artery remained to connect the artery stumps. This study assesses the feasibility to create a completely biodegradable vascular regeneration guide in vivo, able to sequentially orchestrate vascular regeneration events needed for very small artery reconstruction.

Small diameter double layer tubular scaffolds using highly elastic PLCL copolymer for vascular tissue engineering

“…However, the availability of suitable native replacements is limited when multiple conduits are required, especially in patients with diffuse vascular disease. 8 Tissue engineering technology has emerged as a promising approach to address the shortcomings of current therapies. 9 Vascular tissue engineering attempts to create functional small diameter grafts by combining cells with a natural and/ or synthetic scaffold material under suitable culture conditions, resulting in a tubular construct that can be used in vivo.…”

Hyaluronan based porous nano-particles enriched with growth factors for the treatment of ulcers: a placebo-controlled study

“…The particles had a nano-structured porosity that was particularly suitable for absorbing bioactive molecules. HYAFF11 Ò , the benzyl ester of hyaluronic acid (Fidia advanced Biopolymer, Italy), is a biopolymer well known in tissue engineering applications such as in vitro reconstruction of skin, cartilage, and bone, and has been recently used for the in vivo regeneration of small arteries [12][13][14][15][16]. Microparticles, films or plugs prepared from hyaluronan esters have also been evaluated as a novel drug delivery system [17,18].…”

Bioengineered Vascular Scaffolds: The State of the Art

“…In this case, human vascular cells, such as endothelial cells (62) and smooth muscle cells (SMCs) (63), were grown in vitro on benzylic esters of hyaluronic acid (namely HYAFF-11 biomaterials) constructs to develop new tissue-engineered vascular substitutes. Previous in vivo studies (65)(66)(67)(68) confirmed that HYAFF tubes could sequentially orchestrate the vascular regeneration events needed for very small artery reconstruction. HYAFF-11 was shown to be very well tolerated and to elicit no adverse reactions in clinical practice (62,63,69).…”

“…They may also overcome problems related to current vascular implant materials that insufficiently recruit endothelial cells to form a normally functional and confluent endothelium, a key challenge to reinstating vascular homeostasis at the surgical site. An Italian team obtained stimulating results in testing vascular prostheses entirely made of HA in rat and pig experimental models (65)(66)(67)(68). In this case, human vascular cells, such as endothelial cells (62) and smooth muscle cells (SMCs) (63), were grown in vitro on benzylic esters of hyaluronic acid (namely HYAFF-11 biomaterials) constructs to develop new tissue-engineered vascular substitutes.…”