Biology subjects

Barralet, J.

Publications and source records attributed to Barralet, J..

3 recordsLinked to original sources

bioRxiv2026

Venous Angiogenesis and Dermal Fibroblast Augmentation of Decellularized Dermis: Towards Transplantable Dermal Substitutes

The ability to generate vascularized tissue constructs supplied by surgically accessible vessels remains a major limitation in reconstructive tissue engineering. Previous work demonstrated that positioning porous biomaterials around a vein can induce extensive vascular sprouting and generate a vascularized tissue volume without creation of an arteriovenous loop. However, this phenomenon has principally been demonstrated using rigid calcium-phosphate scaffolds, limiting its direct relevance to soft-tissue reconstruction. Here, we investigated whether a flexible decellularized dermal matrix could similarly be vascularized around a single unmodified vein and whether autologous dermal fibroblasts could further enhance this response. Decellularized rat dermis, with or without autologous dermal fibroblast seeding, was implanted either subcutaneously in the dorsal region or around the femoral vein for 8 weeks. Following Microfil perfusion, three-dimensional micro-CT demonstrated an extensive branching vascular network within perivenous constructs. Vessel volume relative to tissue volume was 0.2 +/- 0.1% in subcutaneous constructs without fibroblasts (n = 11) and 0.6 +/- 0.2% with fibroblasts (n = 9), compared with 6.+/- 1.4 % in perivenous constructs without fibroblasts (n = 10) and 7.3+/- 1.2% with fibroblasts (n = 10). Histology and immunohistochemistry similarly showed greater cellular repopulation and substantially higher CD31- and -SMA-positive vessel densities following perivenous implantation. Integrated two-way ANOVA of the same 8-week data confirmed a dominant effect of implantation site across the vascular outcomes, while fibroblast seeding significantly affected vascular volume, dermal remodeling, and nuclear density. The effect of fibroblast seeding on vascular volume was site dependent, with a significant implantation site fibroblast interaction. At 8 weeks, the vascularized dermal construct was completely dissected free from the surrounding tissues while maintaining its connection to the femoral vein. A small superficial incision into the isolated dermis produced visible bleeding, supporting an acute functional connection of the intradermal vascular network to the host circulation while the femoral venous connection was preserved. After flap elevation, perivenous constructs retained substantially greater vascular volume and showed more complete surface healing and organized skin architecture than subcutaneous constructs. Fibroblast seeding accelerated wound closure, while its effect on post-elevation vascular volume depended on implantation site: VV/TV decreased in subcutaneous constructs but increased in perivenous constructs. These findings show that single-vein vascularization can extend from rigid calcium-phosphate biomaterials to a compliant biological extracellular-matrix scaffold and may provide a simplified axial vascularization strategy without arterialization or incorporation of an arterial vessel.

bioengineering↗

bioRxiv2022

Biomaterials, oxygen delivery, necrosis

Inadequate tissue blood supply (e.g., in a wound or a poorly vascularised graft) can result in tissue ischemia and necrosis. As revascularization is a slow process relative to the proliferation of bacteria and the onset and spread of tissue necrosis, extensive tissue damage and loss can occur. Necrosis can spread rapidly, and treatment options are limited such that loss of tissue in ischemic tissue following necrosis onset is considered unavoidable and irreversible. Oxygen delivery from biomaterials exploiting aqueous decomposition of peroxy-compounds has shown some potential in overcoming the supply limitations caused by quite short oxygen diffusion distances in tissues by creating higher concentration gradients than can be attained by air saturated solutions or by distributing oxygen supply throughout a scaffold or construct by using particulate formulations. These have found application in tissue preservation, bioinks, creation of 3D tissue analogues etc. In preclinical models among the more exciting reports was a single study demonstrating reduction of ischemic skin necrosis albeit only short term using short term sub dermal delivery of oxygen below ischemic skin flaps. To explore this effect further, we developed an implantable solid peroxide-biomaterial based system with reduced hydrogen peroxide release by virtue of incorporation of minerals to catalytically decompose it in a much longer flap than examined previously. Blood flow in this flap reduced from essentially normal to essentially zero, along its 9cm length. Without treatment [~]50% of the total flap was necrotic in 2-4 days. In both groups, complete necrosis in the distal third of the flap with no observable flood flow was observed. But in the middle low blood flow region of the flap, treatment did prevent necrosis. This study indicated that subdermal oxygen delivery alone cannot completely mitigate dermal necrosis if no blood flow is present, but it could improve the survival of partially tissue at least in the short term which could find application to augment conventional treatments or to gain time until surgical intervention.

bioengineering↗

bioRxiv2018

Bioinorganic Angiogenesis

Causing a large diameter blood vessel to sprout branches and a capillary network on demand to create a new angiosome is key to harnessing to potential of regenerative medicine and advancing reconstructive surgery. Currently this can only be achieved by connecting a vein graft to an artery by microsurgery, the arteriovenous loop technique (AVL). The arterial blood pressure in the thin-walled vein is thought to drive remodelling to create branches, however the surgical complexity limits the application of the technique. In this study we demonstrate that unexpectedly, a vessel density of luminal branches in excess of that achieved by the surgical AVL approach can be induced simply by placing a vein in contact with a microporous calcium phosphate. Only osteoinductive biomaterials have been reported previously, this is thought to be the first report of an angio-inductive material. Pilot studies indicated that the material type greatly affected the degree of luminal vascularization. Material contact with the vein is not a requirement for luminal angiogenesis of the vein and together these findings point to a bioinorganic effect, wherein the degradation of the material both releases a stimulatory ionic milieu and creates space for the developing angiosome.

bioengineering↗