Cardiovascular disease is the leading cause of death worldwide, with this trend predicted to continue for the foreseeable future. Common disorders are associated with the stenosis or occlusion of ...blood vessels. The preferred treatment for the long-term revascularization of occluded vessels is surgery utilizing vascular grafts, such as coronary artery bypass grafting and peripheral artery bypass grafting. Currently, autologous vessels such as the saphenous vein and internal thoracic artery represent the gold standard grafts for small-diameter vessels (<6 mm), outperforming synthetic alternatives. However, these vessels are of limited availability, require invasive harvest, and are often unsuitable for use. To address this, the development of a tissue-engineered vascular graft (TEVG) has been rigorously pursued. This article reviews the current state of the art of TEVGs. The various approaches being explored to generate TEVGs are described, including scaffold-based methods (using synthetic and natural polymers), the use of decellularized natural matrices, and tissue self-assembly processes, with the results of various
in vivo
studies, including clinical trials, highlighted. A discussion of the key areas for further investigation, including graft cell source, mechanical properties, hemodynamics, integration, and assessment in animal models, is then presented.
Tissue-engineered skin has been in clinical use for 25 years and has developed greatly during this time. This review looks at the role biomaterials need to play in providing for epidermal cover, ...dermal replacement, and epidermal/dermal replacement, and describes the major problems that remain. The majority of biomaterials in clinical use are based on natural or extracted collagen. The clinical challenges in using these materials are highlighted throughout – specifically safety issues, improving the take of cultured cells on wound beds, improving the rate of neovascularization of tissue-engineered skin, and developing scaffolds that resist contraction and fibrosis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This study describes a novel surgical technique of limbal transplantation, which combines the benefits of existing techniques while avoiding their difficulties. Six patients with unilateral and total ...limbal stem cell deficiency following ocular surface burns underwent a single-stage procedure. A 2 × 2 mm strip of donor limbal tissue was obtained from the healthy eye and divided into eight to ten small pieces. After surgical preparation of the recipient ocular surface, these tiny limbal transplants were distributed evenly over an amniotic membrane placed on the cornea. After surgery, a completely epithelialised, avascular and stable corneal surface was seen in all recipient eyes by 6 weeks, and this was maintained at a mean ± SD follow-up of 9.2 ± 1.9 months. Visual acuity improved from worse than 20/200 in all recipient eyes before surgery to 20/60 or better in four (66.6%) eyes, while none of the donor eyes developed any complications. This technique requires less donor tissue than previously used for conventional autografting and does not need a specialist laboratory for cell expansion. Although long-term results are awaited, this simple limbal epithelial transplantation promises to be an easy and effective technique for treating unilateral limbal stem cell deficiency following ocular burns.
Skin has a highly regulated pH environment of around pH 7.2 but with an acid barrier mantle of around pH 5.5. Trauma, inflammation, and infection are all thought to disrupt this pH environment but ...the lack of a non-invasive technique to measure pH within discrete locations within skin has hindered investigating what role pH plays in wound healing. In this study, a confocal Raman microspectroscopy method was used for measuring pH in a 3D tissue engineered model of human skin (TE-skin) and evaluated for its ability to detect changes in pH in response to wounding, inflammation and bacterial infection. The state of protonation of phosphate groups within the TE-skin was used to indicate pH in a non-destructive manner exploring depths of skin from the stratum corneum to 600 microns into the dermis. Deliberate wounding or inflammation (induced by IL-17) resulted in a loss of the acid mantle. Detailed scanning of TE-skin infected with Staphylococcus aureus or Pseudomonas aeruginosa revealed heterogeneous pH microenvironments ranging in size from 10 × 10 to 50 × 100 microns and ranging from pH 5 to 9. These microenvironments were not detected if an average pH for the TE-skin model was used.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
Tissue-engineered skin is now a reality. For patients with extensive full-thickness burns, laboratory expansion of skin cells to achieve barrier function can make the difference between life and ...death, and it was this acute need that drove the initiation of tissue engineering in the 1980s. A much larger group of patients have ulcers resistant to conventional healing, and treatments using cultured skin cells have been devised to restart the wound-healing process. In the laboratory, the use of tissue-engineered skin provides insight into the behaviour of skin cells in healthy skin and in diseases such as vitiligo, melanoma, psoriasis and blistering disorders.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Guided bone regeneration is a common dental implant treatment where a barrier membrane (BM) is used between epithelial tissue and bone or bone graft to prevent the invasion of the fast-proliferating ...epithelial cells into the defect site to be able to preserve a space for infiltration of slower-growing bone cells into the periodontal defect site. In this study, a bilayer polycaprolactone (PCL) BM was developed by combining electrospinning and emulsion templating techniques. First, a 250 µm thick polymerised high internal phase emulsion (polyHIPE) made of photocurable PCL was manufactured and treated with air plasma, which was shown to enhance the cellular infiltration. Then, four solvent compositions were investigated to find the best composition for electrospinning a nanofibrous PCL barrier layer on PCL polyHIPE. The biocompatibility and the barrier properties of the electrospun layer were demonstrated over four weeks in vitro by histological staining. Following in vitro assessment of cell viability and cell migration, cell infiltration and the potential of PCL polyHIPE for supporting blood vessel ingrowth were further investigated using an ex-ovo chick chorioallantoic membrane assay. Our results demonstrated that the nanofibrous PCL electrospun layer was capable of limiting cell infiltration for at least four weeks, while PCL polyHIPE supported cell infiltration, calcium and mineral deposition of bone cells, and blood vessel ingrowth through pores.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Biomaterials need to be vigorously tested at every stage of preclinical development. As demand for in vivo culture environments continues to increase, traditional animal models are often technically ...complex, ethically undesirable, time-consuming, and resource intensive and thus present a barrier to high throughput screening. The chick chorioallantoic membrane (CAM) assay has long been used to study the effects of drugs on angiogenesis in vivo, providing researchers with a readily available, accessible, self-sustaining, and high throughput screen without requiring animal facilities. It has also been recognized as an in vivo assay to test initial tissue response to biomaterials; however it has not yet gained widespread acceptance. This could be due to lack of specific protocols on how to optimize this assay to specifically test biomaterials. Here we describe how the ex ovo (shell-less) CAM assay can be effectively used to study the angiogenic potential and initial tissue response to biomaterials. In comparison to alternative in vivo approaches, this technique provides additional advantages to the researcher as it allows better visualization of implanted biomaterials and the ability to implant several samples simultaneously enabling combinatorial biomaterial assays to be conducted.
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IJS, KILJ, NUK, PNG, UL, UM
When germ-free cell cultures became a laboratory routine, hopes were high for using this novel technology for treatment of diseases or replacement of cells in patients suffering from injury, ...inflammation, or cancer or even refreshing cells in the elderly. Today, more than 50 years after the first successful bone marrow transplantation, clinical application of hematopoietic stem cells is a routine procedure, saving the lives of many every day. However, transplanting other than hematopoietic stem and progenitor cells is still limited to a few applications, and it mainly applies to mesenchymal stromal cells (MSCs) isolated from bone marrow. But research progressed and different trials explore the clinical potential of human MSCs isolated from bone marrow but also from other tissues including adipose tissue. Recently, MSCs isolated from bone marrow (bmMSCs) were shown to be a blend of distinct cells and MSCs isolated from different tissues show besides some common features also some significant differences. This includes the expression of distinct antigens on subsets of MSCs, which was utilized recently to define and separate functionally different subsets from bulk MSCs. We therefore briefly discuss differences found in subsets of human bmMSCs and in MSCs isolated from some other sources and touch upon how this could be utilized for cell-based therapies.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Introduction of pro-angiogenic cells into tissue-engineered (TE) constructs (prevascularisation) is a promising approach to overcome delayed neovascularisation of such constructs post-implantation. ...Accordingly, in this study, we examined the contribution of human dermal microvascular endothelial cells (HDMECs) and human dermal fibroblasts (HDFs) alone and in combination on the formation of new blood vessels in ex-ovo chick chorioallantoic membrane (CAM) assay.
Poly-3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV) and polycaprolactone (PCL) were first examined in terms of their physical, mechanical, and biological performances. The effect of gelatin coating and co-culture conditions on enhancing endothelial cell viability and growth was then investigated. Finally, the angiogenic potential of HDMECs and HDFs were assessed macroscopically and histologically after seeding on simple electrospun PHBV scaffolds either in isolation or in indirect co-culture using an ex-ovo CAM assay.
The results demonstrated that PHBV was slightly more favourable than PCL for HDMECs in terms of cell metabolic activity. The gelatin coating of PHBV scaffolds and co-culture of HDMECs with HDFs both showed a positive impact on HDMECs viability and growth. Both cell types induced angiogenesis over 7 days in the CAM assay either in isolation or in co-culture. The introduction of HDMECs to the scaffolds resulted in the production of more blood vessels in the area of implantation than the introduction of HDFs, but the co-culture of HDMECs and HDFs gave the most significant angiogenic activity.
Our findings showed that the in vitro prevascularisation of TE constructs with HDMECs and HDFs alone or in co-culture promotes angiogenesis in implantable TE constructs.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Corneal stem cell niches are located within the limbus of the eye and are believed to play an important role in corneal regeneration. These niches are often lost in corneal disease or trauma. Our ...work explores the design of artificial limbal stem cell niches by the fabrication of biodegradable electrospun rings containing bespoke microfeatures. In creating artificial niches, we seek to provide a physically protective environment for limbal cells to act as a cell reservoir for tissue regeneration purposes. This study describes the first step in this challenge to produce structures which structurally approximate to the limbal niches. This was achieved using a combination of electrospinning and microfabrication. Initial microfabricated structures were developed using microstereolithography via a layer-by-layer photocuring approach based on the patterning of photocurable polymers, in this case polyethylene glycol diacrylate. This was then used as a template on which to electrospin a biodegradable membrane of poly(lactic-co-glycolic acid) 50:50, which incorporates the features of the underlying microfabricated structures. The study describes preliminary evaluation of these constructs using rabbit limbal epithelial and stromal cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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