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Chronic wounds, including diabetic and venous ulcers, represent disruption of normal healing processes resulting in a pathological state of nonhealing cutaneous inflammation. They place an increasingly significant economic burden on healthcare providers as their prevalence is rising in keeping with an aging population. Current treatment modalities are slow acting and resource intensive. Bioengineered skin substitutes from autogenic, allogenic, or xenogenic sources have emerged as a new and alternative therapeutic option. A range of such products is licensed for clinical use, which differ in terms of structure and cellular content. Placed directly onto a prepared wound bed, skin substitutes may stimulate or accelerate healing by promoting revascularization, cellular migration, and repopulation of wound fields through provision of an appropriate scaffold material to facilitate these processes. Products containing fetal or autologous cells also benefit from early release of bioactive molecules including growth factors and cytokines. To date, limited numbers of randomized controlled trials studying skin substitutes have been published but evidence from case series and case-control studies is encouraging. This review discusses chronic wound biology, the influence that skin substitutes can exert on this environment, the products currently available, and examines the evidence for their use in chronic wound management., (© 2013 by the Wound Healing Society.)

Conventionally used vascular grafts such as polyester (Dacron) or expanded polytetrafluoroethylene perform inadequately as small-diameter vascular bypass grafts (SDBGs). SDBGs, which can maintain long-term patency and those that could potentially evolve with the somatic growth, are highly desirable in vascular surgery and thus research into tissue-engineered blood vessels (TEBVs) is of keen interest. A TEBV was developed by seeding endothelial cells onto a collagen matrix that was cross-linked and contracted by smooth muscle cells (SMCs). A polyester graft served as a scaffold. Recovery studies (12 TEBVs and seven controls) were carried out to assess in vivo endothelialization and long-term patency of TEBVs. Hemodynamic observations indicated para-anastomotic turbulences and high shear stress at anastomosis. Recovery studies demonstrated confluent endothelialization, thrombus-free surfaces, and patent TEBVs in all cases. Graft incorporation and neovascularization of the scaffold occurred in both hybrid and control grafts. However, thickened neointima formation occurred in TEBV grafts, which was most likely caused by the rigidity of polyester scaffold. Significant perigraft inflammatory changes could be observed in both TEBVs and control grafts at 1, 4, and 8 weeks. In conclusion, the TEBVs demonstrated satisfactory performance as an infra-renal-aortic graft in a porcine model. The TEBV serves as a promising model and facilitates the development of a TEBV in a clinical setting, potentially with human stem cells and with more biocompatible, biodegradable scaffolds that are mechanically more compliant with natural vessels., (Copyright © 2011 International Union of Biochemistry and Molecular Biology, Inc.)

Background: Tissue engineering techniques have been employed successfully in the management of wounds, burns and cartilage repair. Current prosthetic alternatives to autologous vascular bypass grafts remain poor in terms of patency and infection risk. Growing biological blood vessels has been proposed as an alternative., Methods: This review is based on a literature search using Medline, PubMed, ISIS and CAS of original articles and reviews, and unpublished material and abstracts., Results and Conclusions: Complete incorporation into host tissues and the maintenance of a viable and self-renewing endothelial layer are the fundamental goals to be achieved when developing a tissue-engineered blood vessel. Sourcing of cells and modulating their interaction with extracellular matrix and supporting scaffold have been the focus of intense research. Although the use of tissue-engineered blood vessels in humans is so far limited, advances in our knowledge of stem cell precursors and the development of new biomaterials should enable this technology to reach routine clinical practice within a decade., (Copyright (c) 2006 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

In situ tissue engineering using shear-stress preconditioning and adhesive biomolecules is a new approach to autologous tissue engineering. In the present study, novel tissue-engineering grafts (TEGs) were preconditioned within an in vitro pulsatile flow circuit, with and without the addition of fibronectin (FN), to establish whether low-shear-stress conditions promoted endothelial cell (EC) retention and differentiation. TEGs ( n =24) were generated by the contraction and compaction of collagen(I) by porcine aortic smooth-muscle cells (SMCs) on to a compliant polyester graft scaffold. ECs were radiolabelled with [(111)In]indium tropolonate and seeded on to the luminal surface of the TEGs. Following organ culture in a bioreactor (7 days), TEGs were split into four groups ( n =six TEGs per group): Group A acted as controls with TEGs unmodified and seeded with radiolabelled ECs; Group B underwent luminal pre-coating with FN (75 microg/ml) prior to EC seeding; Group C underwent preconditioning within a pulsatile flow circuit at 10-20 microN (1-2 dyn)/cm(2) for 7 days prior to EC seeding, and Group D TEGs were preconditioned for 7 days at 1-2 dyn/cm(2), followed by luminal pre-coating with FN prior to EC seeding. The resistance to physiological shear stress of the seeded ECs was assessed using a gamma-radiation counter within a physiological flow circuit producing an arterial waveform with a mean shear stress of 93.2 microN (9.32 dyn)/cm(2). Environmental scanning electron microscopy (ESEM) was used to determine the distribution and degree of differentiation of the attached Ecs, and tissue-type-plasminogen-activator (tPA) assays provided a measure of function and viability. EC resistance to shear stress at 93.2 microN/cm(2) was significantly enhanced by a period of preconditioning (Group C) at 10-20 microN/cm(2), surface modification with FN (Group B), or both (Group D) when compared with control grafts (Group A). However, TEGs coated with FN whether preconditioned (Group D) or not (Group B) demonstrated the best results for EC retention. ESEM demonstrated near-confluent differentiated flattened ECs in both these cases. EC function was demonstrated by a steady increase in tPA production. Low-shear-stress preconditioning of TEGs enhances EC retention in vitro with an additional advantage demonstrated by pre-treatment with FN prior to endothelialization. These findings may be exploited in the development of tissue-engineered constructs to maintain a confluent endothelial lining.