Hyaluronan‐based scaffold for in vivo regeneration of the rat vena cava: Preliminary results in an animal model

Abstract

The aim of this study was to develop a prosthetic graft that could perform as a small-diameter vascular conduit for vein regeneration. The difficulty of obtaining significant long-term patency and good wall mechanical strength in vivo has been a significant obstacle in achieving small-diameter vein prostheses. Fifteen Male Wistar rats weighing 250-350 g were used. Tubular structures of hyaluronan (HYAFF-11 tubules, 2 mm diameter, and 1.5 cm length) were implanted in the vena cava of rats as temporary absorbable guides to promote regeneration of veins. Performance was assessed at 30, 60, and 90 days after surgery by histology (hematoxylin-eosin and Weighert solution) and immunohistochemistry (antibodies to von Willebrand factor and to Myosin Light-Chain Kinase). These experiments resulted in two novel findings: (1) sequential regeneration of vascular components led to complete vein wall regeneration 30 days after surgery; (2) 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 4 months after implantation, at which time, a new vein remained to connect the vein stumps. This work demonstrates the complete vena cava regeneration inside the hyaluronic acid-based prosthesis, opening new perspective of microsurgical applications, like replantation of the upper limb, elongation of vascular pedicle of free flaps, cardiovascular surgery, and pediatric microvascular surgery.

Elastic, double-layered poly (l-lactide-co-ϵ-caprolactone) scaffold for long-term vascular reconstruction

“…18,28,29 In a previous study, we confirmed that a PLCL scaffold has similar compliance to native arteries that of its PTFE counterpart. 4,36,37 The vascular grafts degraded appropriately so as to maintain the blood pressure and induce regeneration over time as shown in Table 1. 30 In vascular surgery, expanded PTFE or Dacron is usually used clinically; however, these synthetic materials do not degrade in the body.…”

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.…”

Biodegradable polymers for dental tissue engineering and regeneration

“…To overcome this limitation, HA is cross-linked with ethyl esters, benzyl esters, or other biodegradable polymers to enhance the mechanical properties while retaining excellent biocompatibility [368,369]. Such HA hydrogels are extremely versatile and can be fabricated into sheets, membranes, sponges, tubes, fibers, and scaffolds for wound healing [370], regeneration of the trachea [371], cartilage [372], vasculature [373], and nerve tissues [374]. HA is also available in the form of nanoparticles to deliver chemotherapeutics and other drugs [375,376].…”