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Harrow on the Hill, United Kingdom
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Gerhardt L.-C.,Imperial College London | Widdows K.L.,NPIMR | Erol M.M.,Technical University of Istanbul | Nandakumar A.,Xeltis B.V. | And 4 more authors.
Journal of Biomedical Materials Research - Part A | Year: 2013

In this study, the in vivo recellularization and neovascularization of nanosized bioactive glass (n-BG)-coated decellu-larized trabecular bone scaffolds were studied in a rat model and quantified using stereological analyses. Based on the highest amount of vascular endothelial growth factor (VEGF) secreted by human fibroblasts grown on n-BG coatings (0-1.245 mg/cm 2), decellularized trabecular bone samples (porosity: 43-81%) were coated with n-BG particles. Grown on n-BG particles at a coating density of 0.263 mg/cm2, human fibroblasts produced 4.3 times more VEGF than on uncoated controls. After 8 weeks of implantation in Sprague-Dawley rats, both uncoated and n-BG-coated samples were well infiltrated with newly formed tissue (47-48%) and blood vessels (3-4%). No significant differences were found in cellularization and vascularization between uncoated bone scaffolds and n-BG-coated scaffolds. This finding indicates that the decellularized bone itself may exhibit growth-promoting properties induced by the highly interconnected pore microarchitecture and/or proteins left behind on decellularized scaffolds. Even if we did not find proangiogenic effects in n-BG-coated bone scaffolds, a bioactive coating is considered to be beneficial to impart osteoinductive and osteoconductive properties to decellularized bone. n-BG-coated bone grafts have thus high clinical potential for the regeneration of complex tissue defects given their ability for recellularization and neovascularization. © 2012 Wiley Periodicals, Inc.


Nowocin A.K.,NPIMR | Southgate A.,NPIMR | Shurey S.,NPIMR | Sibbons P.,NPIMR | And 3 more authors.
Journal of Tissue Engineering and Regenerative Medicine | Year: 2016

Biologically derived scaffolds are becoming viable treatment options for tissue/organ repair and regeneration. A continuing hurdle is the need for a functional blood supply to and from the implanted scaffold. We have addressed this problem by constructing an acellular ileal scaffold with an attached vascular network suitable for implantation and immediate reperfusion with the host's blood. Using a vascular perfusion approach, a segment of porcine ileum up to 30cm long, together with its attached vasculature, was decellularized as a single entity. The quality of the decellularized scaffold was assessed histologically and using molecular tools. To establish vascular perfusion potentials of the scaffold, a right-sided nephrectomy and end-to-end anastomosis of the decellularized scaffold's vasculature to a renal artery and vein were performed in a pig of similar size to the donor animal. Lengths of ileal scaffold, together with its attached vasculature, were successfully decellularized, with no evidence of intact cells/nuclear material or collagen degradation. The scaffold's decellularized vascular network demonstrated optimum perfusion at 1, 2 and 24h post-implantation and the mesenteric arcade remained patent throughout the assessment. The 1, 2 and 24h explanted scaffolds demonstrated signs of cellular attachment, with cells positive for CD68 and CD133 on the vascular luminal aspect. It is possible to decellularize clinically relevant lengths of small intestine, together with the associated vasculature, as a single segment. The functional vascular network may represent a route for recellularization for future regeneration of bowel tissue for patients with short bowel syndrome. © 2016 John Wiley & Sons, Ltd.


Nowocin A.K.,NPIMR | Southgate A.,NPIMR | Gabe S.M.,St Marks Hospital | Ansari T.,NPIMR
Journal of Tissue Engineering and Regenerative Medicine | Year: 2016

The aim of this study was to decellularize a 30cm long segment of porcine small intestine, determine its in vivo behaviour and assess the type of immunological reaction it induces in a quantitative manner. A segment of porcine ileum up to 30cm long, together with its attached vasculature, was decellularized via its mesenteric arcade as a single entity. The quality of the acellular scaffold was assessed histologically and using molecular tools. The host response to the scaffold was evaluated in a rodent model. Stereological techniques were incorporated into quantitative analysis of the phenotype of the macrophages infiltrating the scaffold in vivo. Lengths of ileal scaffold, together with its attached vasculature, were successfully decellularized, with no evidence of intact cells and DNA or collagen and GAGs overdegradation. Analysis of explants harvested over 2months postimplantation revealed full-thickness recellularization and no signs of foreign body or immune reactions. Macrophage profiling proved that between weeks 4 and 8 in vivo there was a switch from an M1 (pro-inflammatory) to an M2 (pro-remodelling) type of response. We show here that the decellularization process results in a biocompatible and non-toxic matrix that upon implantation triggers cellular infiltration and angiogenesis, primarily characterized by a pro-remodelling type of mononuclear response, without inducing foreign body reaction or fibrosis. © 2016 John Wiley & Sons, Ltd.


PubMed | University College London and NPIMR
Type: | Journal: Journal of biomedical materials research. Part B, Applied biomaterials | Year: 2016

There is a clinical need to provide replacement tracheal tissue for the pediatric population affected by congenital defects, as current surgical solutions are not universally applicable. A potential solution is to use tissue engineered scaffold as the framework for regenerating autologous tissue. Rabbit trachea were used and different detergents (Triton x-100 and sodium deoxycholate) and enzymes (DNAse/RNAse) investigated to create a decellularization protocol. Each reagent was initially tested individually and the outcome used to design a combined protocol. At each stage the resultant scaffold was assessed histologically, molecularly for acellularity and matrix preservation. Immunogenicity of the final scaffold was assessed by implantation into a rat model for 4weeks. Both enzymes and detergents were required to produce a completely acellular (DNA content 42.78ng/mg) scaffold with preserved collagen and elastin however, GAG content were reduced (8.781.35 vs. 5.54.8). Following in vivo implantation the scaffold elicited minimal immune response and showed significant cellular infiltration and vasculogenesis. The luminal aspect of the implanted scaffold showed infiltration of host derived cells, which were positive for pan cytokeratin. It is possible to create biologically derived biocompatible scaffolds to address specific pediatric clinical problems. 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2016.


PubMed | Friedrich - Alexander - University, Erlangen - Nuremberg, Imperial College London, University of Oxford and NPIMR
Type: Journal Article | Journal: Journal of biomaterials applications | Year: 2015

Off-the-shelf availability of tissue-engineered skin constructs, tailored by different combinations of reagents to produce a highly preserved biological matrix is often the only means to help patients suffering skin damage. This study assessed the effect of five different decellularisation methods on porcine dermal scaffolds with regard to matrix composition, biomechanical strength, and cytotoxicity using an in vitro biocompatibility assay. Results demonstrated that four out of the five tested decellularisation protocols were efficient in producing acellular scaffolds. Nevertheless, decellularisation method using osmotic shock without enzymatic digestion showed to be efficient not only in removing cellular material and debris from dermal scaffolds but was also beneficial in the preservation of extracellular matrix components (glycosaminoglycans and collagen). Histological assessment revealed that the dermal architecture of coarse collagen bundles was preserved. Examinations by scanning electron microscopy and transmission electron microscopy showed that the arrangement and ultrastructure of collagen fibrils in the scaffolds were retained following non-enzymatic method of decellularisation and also after collagen crosslinking using genipin. Moreover, this decellularised scaffold was not only shown to be biologically compatible when co-cultured with bone marrow-derived mesenchymal stem cells and fibroblasts, but also stimulated the cells to release trophic factors essential for tissue regeneration.

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