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Bone and cartilage craniofacial defects due to trauma or congenital deformities pose a difficult problem for reconstructive surgeons. Human adipose stem cells (ADSCs) can differentiate into bone and cartilage and together with suitable scaffolds could provide a promising system for skeletal tissue engineering. It has been suggested that nanomaterials can direct cell behavior depending on their surface nanotopographies. Thus, this study examined whether by altering a nanoscaffold surface using radiofrequency to excite gases, argon (Ar), nitrogen (N 2 ) and oxygen (O 2 ) with a single step technique, we could enhance the osteogenic and chondrogenic potential of ADSCs. At 24 h, Ar modification promoted the highest increase in ADSCs adhesion as indicated by upregulation of vinculin and focal adhesion kinase (FAK) expression compared to O 2 and N 2 scaffolds. Furthermore, ADSCs on Ar-modified nanocomposite polymer POSS-PCU scaffolds upregulated expression of bone markers, alkaline phosphatase, collagen I and osteocalcin after 3 weeks. Cartilage markers, aggrecan and collagen II, were also upregulated on Ar-modified scaffolds at the mRNA and protein level. Finally, all plasma treated scaffolds supported tissue ingrowth and angiogenesis after grafting onto the chick chorioallantoic membrane. Ar promoted greater expression of vascular endothelial growth factor and laminin in ovo compared to O 2 and N 2 scaffolds as shown by immunohistochemistry. This study provides an important understanding into which surface chemistries best support the osteogenic and chondrogenic differentiation of ADSCs that could be harnessed for regenerative skeletal applications. Argon surface modification is a simple tool that can promote ADSC skeletal differentiation that is easily amenable to translation into clinical practice., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs offers a paradigm shift in regenerative medicine. The use of either embryonic stem cells (ESC) or induced pluripotent stem cells (iPSC) in clinical situations is limited because of regulations and ethical considerations even though these cells are theoretically highly beneficial. While clinically, adipose-derived stem cells (ADSCs) are one of the most widely used types of stem cells used more than five years in clinically setting. It has many advantages including; yields a high number of ADSCs per volume of tissue, high rate of proliferation, anti-fibrotic, anti-apoptotic, anti-inflammation, immunomodulation, and paracrine mechanisms have been demonstrated in various preclinical studies. It is much easier to harvest compared with bone marrow stem cells. Results of clinical studies have demonstrated the potentials of ADSCs for stem cells therapy for a number of clinical disorders. The aim of this paper was to provide an update on the most recent developments of ADSCs, by highlighting the properties and features of ADSCs, critically discussing its clinical benefit and its clinical trials in treatment and regeneration. This is a multi-billion dollars industry with huge interest to clinician, academia and industries., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Deformities of the upper airways, including those of the nose and throat, are typically corrected by reconstructive surgery. The use of autologous somatic stem cells for repair of defects could improve quality and outcomes of such operations. The present study explored the ability of paediatric adipose-derived stem cells (pADSCs), a readily available source of autologous stem cells, to generate a cartilage construct with a functional epithelium. Paediatric ADSCs seeded on the biodegradable nanocomposite polymer, polyhedral oligomeric silsesquioxane poly(ϵ-caprolactone-urea) urethane (POSS-PCL), proliferated and differentiated towards mesenchymal lineages. The ADSCs infiltrated three-dimensional POSS-PCL nanoscaffold and chondroid matrix was observed throughout chondrogenically induced samples. In ovo chorioallantoic membrane-grafted ADSC-nanoscaffold composites were enwrapped by host vessels indicating good compatibility in an in vivo system. Furthermore, pADSCs could be induced to transdifferentiate towards barrier-forming epithelial-like cells. By combining differentiation protocols, it was possible to generate epithelial cell lined chondrogenic micromasses from the same pADSC line. This proof-of-concept study appears to be the first to demonstrate that individual pADSC lines can differentiate towards two different germ lines and be successfully co-cultured. This has important implications for bioengineering of paediatric airways and further confirms the plastic nature of ADSCs. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Despite great advances in tissue engineering, there have been very few reports on the successful clinical use of small-diameter tissue-engineered vascular grafts (TEVGs). Small-diameter (<6 mm internal diameter) is considered as unmet clinical need. This review critically examines the role of stem cells that have been proposed and used in development of TEVGs, and assesses the viability of such graft to clinical pathway. With over 20 years of expertise in development of bypass graft and a number of grafts under clinical trial, this team will offer potential areas for future research that may help improve the current state-of-the-art technology.

The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs offers a paradigm shift in plastic and reconstructive surgery. The use of either embryonic stem cells (ESC) or induced pluripotent stem cells (iPSC) in clinical situations is limited because of regulations and ethical considerations even though these cells are theoretically highly beneficial. Adult mesenchymal stem cells appear to be an ideal stem cell population for practical regenerative medicine. Among these cells, adipose-derived stem cells (ADSC) have the potential to differentiate the mesenchymal, ectodermal and endodermal lineages and are easy to harvest. Additionally, adipose tissue yields a high number of ADSC per volume of tissue. Based on this background knowledge, the purpose of this review is to summarise and describe the proliferation and differentiation capacities of ADSC together with current preclinical data regarding the use of ADSC as regenerative tools in plastic and reconstructive surgery., (© 2016 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

The treatment of full thickness skin loss, which can be extensive in the case of large burns, continues to represent a challenging clinical entity. This is due to an on-going inability to produce a suitable tissue engineered substrate that can satisfactorily replicate the epidermal and dermal in vivo niches to fulfil both aesthetic and functional demands. The current gold standard treatment of autologous skin grafting is inadequate because of poor textural durability, scarring and associated contracture, and because of a paucity of donor sites in larger burns. Tissue engineering has seen exponential growth in recent years with a number of 'off-the-shelf' dermal and epidermal substitutes now available. Each has its own limitations. In this review, we examine normal wound repair in relation to stem/progenitor cells that are intimately involved in this process within the dermal niche. Endothelial precursors, in particular, are examined closely and their phenotype, morphology and enrichment from multiple sources are described in an attempt to provide some clarity regarding the controversy surrounding their classification and role in vasculogenesis. We also review the role of the next generation of cellularized scaffolds and smart biomaterials that attempt to improve the revascularisation of artificial grafts, the rate of wound healing and the final cosmetic and functional outcome., (Copyright © 2013 John Wiley & Sons, Ltd.)

Context: Congenital heart disease is a leading cause of death in the first year, with an incidence of 1.5 million worldwide. It can be treated with bypass surgery, but due to the limited availability of autologous grafts, there has been research into developing a completely tissue-engineered vascular graft. Our group has developed a small diameter, biodegradable nanocomposite graft which is non-thrombogenic and biostable., Objectives: This study looks at the effects of the growth factors, TGF-β1 and BMP-4 on bone marrow-derived stem cell (BMSC) morphology on a POSS PCL scaffold., Materials and Methods: BMSCs were seeded onto a new nanocomposite of POSS (polyhedral oligomeric silsesquioxane) and PCL (poly[caprolactone-urea]urethane) and TGF-β1 and BMP-4 were used to induce differentiation of the cells to smooth muscle cells. The distribution of the cells was examined using confocal and electron microscopies and the phenotype of the cells was assessed using immunohistochemistry., Results: It was found that growth factor induction led to a decrease in cell growth on POSS PCL as compared to that of the control surface, and confocal microscopic analysis showed less cytoskeleton reorganization of these cells. After immunohistochemistry analysis, the BMSCs showed no differentiation to smooth muscle cells., Discussion: Growth factor induction on the static scaffold discs led to a change in morphology, with less spreading of the cells, a lower proliferation rate and no differentiation into SMCs. These findings can be attributed to the POSS PCL being manufactured by a coagulation technique, resulting in a structure with low stiffness.

Background: Adipose-derived stem cells (ADSC) can be readily extracted from adipose tissue, expanded in vitro, and have the capacity to differentiate into multiple cell lineages. This makes this cell type of great interest to the field of regenerative medicine. This study focuses on the isolation and characterisation of ADSC and their differentiation into adipocytes in a 3D microtissue model., Methods: Human ADSC were isolated from abdominal adipose tissue and characterised using multiparameter flow cytometry. ADSC were then expanded in culture and used to produce 3D scaffold-free micro-tissue. Adipogenic differentiation potential of micro-tissue constructs were subsequently characterised using Oil Red O staining., Results: Flow cytometric analysis showed ADSC were uniformly positive for CD34, CD73, CD90, and CD105, and negative for CD19, CD14, and CD45. The cells were functionally induced into adipocytes in the presence of appropriate conditioned media., Conclusion: We have demonstrated that adipose-derived stem cells have the ability to form of microtissue and survive in vitro. We postulate that in the future this will result in an ADSC population which is injectable and can extend the delivery options of current stem cell-based therapies., (Copyright © 2014. Published by Elsevier Ltd.)

Craniofacial malformations, have devastating psychosocial implications for many adults and children and causes huge socioeconomic burden. Currently craniofacial defects require soft tissue transfer, bone grafting techniques or difficult procedures such as microvascular free flaps. Such tissues are often limited in quantity, their harvest causes secondary large donor site defects and they lack the capability to fully restore previous form and function. Stem cell technology is being utilised for various tissue and organs of the body and consequently surgeons are eager to transfer these principles for craniofacial surgery. Adipose derived stem cells (ADSCs) are an exciting stem cell source for craniofacial surgeons due to their easy and painless isolation, relatively large abundance and familiarity with the harvesting procedure. ADSCs also have multiple desirable properties including adipogenic, osteogenic and chondrogenic potential, enhancement of angiogenesis and immunodulatory function. Due to these advantageous characteristics, ASDCs have been explored to repair craniofacial bone, soft tissue and cartilage. The desirable characteristics of ADSCs for craniofacial surgical applications will be explained. We report the experimental and clinical studies that have explored the use of ADSCs for bone, cartilage and soft tissue craniofacial defects. We conclude by establishing the key questions that are preventing the clinical application of ADSCs for craniofacial surgery.

Superparamagnetic iron oxide nanoparticles (SPIONs) are an exciting advancement in the field of nanotechnology. They expand the possibilities of noninvasive analysis and have many useful properties, making them potential candidates for numerous novel applications. Notably, they have been shown that they can be tracked by magnetic resonance imaging (MRI) and are capable of conjugation with various cell types, including stem cells. In-depth research has been undertaken to establish these benefits, so that a deeper level of understanding of stem cell migratory pathways and differentiation, tumor migration, and improved drug delivery can be achieved. Stem cells have the ability to treat and cure many debilitating diseases with limited side effects, but a main problem that arises is in the noninvasive tracking and analysis of these stem cells. Recently, researchers have acknowledged the use of SPIONs for this purpose and have set out to establish suitable protocols for coating and attachment, so as to bring MRI tracking of SPION-labeled stem cells into common practice. This review paper explains the manner in which SPIONs are produced, conjugated, and tracked using MRI, as well as a discussion on their limitations. A concise summary of recently researched magnetic particle coatings is provided, and the effects of SPIONs on stem cells are evaluated, while animal and human studies investigating the role of SPIONs in stem cell tracking will be explored.

Replacement of irreversibly damaged organs due to chronic disease, with suitable tissue engineered implants is now a familiar area of interest to clinicians and multidisciplinary scientists. Ideal tissue engineering approaches require scaffolds to be tailor made to mimic physiological environments of interest with specific surface topographical and biological properties for optimal cell-material interactions. This study demonstrates a single-step procedure for inducing biomimicry in a novel nanocomposite base material scaffold, to re-create the extracellular matrix, which is required for stem cell integration and differentiation to mature cells. Fumed silica nanoparticle mediated procedure of scaffold functionalization, can be potentially adapted with multiple bioactive molecules to induce cellular biomimicry, in the development human organs. The proposed nanocomposite materials already in patients for number of implants, including world first synthetic trachea, tear ducts and vascular bypass graft., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Scaffold cellularization for cartilage engineering can aid implant properties, their retention and minimize repeated intervention, particularly in paediatric reconstructive craniofacial surgery. We developed novel bionanoscaffolds using paediatric adipose tissue-derived stem cells (hADSCs), an accessible autologous cell source, and POSS-PCU. Little is known about cellular responses to this nanomaterial, though it was used in human. We assessed: 1) POSS-PCU cellularization and bioaffinity to hADSCs; 2) hADSC chondrogenic differentiation ability in POSS-PCU; 3) whether bionanoscaffolds became encased within a vascular network and/or vascularised. POSS-PCU supported ADSC survival and proliferation and their migration and differentiation into cartilage within the nanoscaffold. Furthermore, after CAM-grafting, bionanoscaffolds were rapidly surrounded by blood vessels without any apparent negative reaction and erythrocytes of host origin were detected inside the scaffold, suggesting invasion from some capillaries. Altogether, this study demonstrates that POSS-PCU displays excellent bioactivity and hADSC/POSS-PCU bionanoscaffolds offer much promise for autologous cell-based tissue engineering for clinical applications., From the Clinical Editor: In this study, human adipose tissue derived stem cells were used in combination with POSS-PCU nanoscaffolds to generate cartilage tissue demonstrating excellent bioactivity for autologous cell-based tissue engineering for clinical applications., (© 2013.)

With the continuous and expanding use of implantable biomaterials in a clinical setting, this study aims to elucidate the influence of sterilization techniques on the material surface and bulk properties of two polyurethane nanocomposite biomaterials. Both solid samples and porous membranes of nondegradable polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane (POSS-PCU) and a biodegradable poly(caprolactone-urea) urethane (POSS-PCL) were examined. Sterilization techniques included conventional steam sterilization (autoclaving), gamma irradiation, and disinfection via incubating with ethanol (EtOH) for 10 min or 24 h. After treatment, the samples were examined using gel permeation chromatography (GPC), attenuated total reflectance Fourier transform infrared spectroscopy, and tensiometry. Cytotoxicity was evaluated through the culture of endothelial progenitor cells and the efficacy of sterilization method was determined by incubating each sample in tryptone soya broth and fluid thioglycollate medium for cultivation of microorganisms. Although EtOH did not affect the material properties in any form, the samples were found to be nonsterile with microbial growth detected on each of the samples. Gamma irradiation was not only effective in sterilizing both POSS-PCU and POSS-PCL but also led to minor material degradation and displayed a cytotoxic effect on the cultured cells. Autoclaving was found to be the optimal sterilization technique for both solid and porous membranes of the nondegradable POSS-PCU samples as it was successful in sterilizing the samples, displayed no cytotoxic side effects and did not degrade the material. However, the biodegradable POSS-PCL was not able to withstand the harsh environment during autoclaving, resulting in it losing all structural integrity., (Copyright © 2013 Wiley Periodicals, Inc., a Wiley Company.)

Objective: To investigate manufacturing smooth muscle cells (SMCs) for regenerative bladder reconstruction from differentiation of endometrial stem cells (EnSCs), as the recent discovery of EnSCs from the lining of women's uteri, opens up the possibility of using these cells for tissue engineering applications, such as building up natural tissue to repair prolapsed pelvic floors as well as building urinary bladder wall., Materials and Methods: Human EnSCs that were positive for cluster of differentiation 146 (CD146), CD105 and CD90 were isolated and cultured in Dulbecco's modified Eagle/F12 medium supplemented with myogenic growth factors. The myogenic factors included: transforming growth factor β, platelet-derived growth factor, hepatocyte growth factor and vascular endothelial growth factor. Differentiated SMCs on bioabsorbable polyethylene-glycol and collagen hydrogels were checked for SMC markers by real-time reverse-transcriptase polymerase chain reaction (RT-PCR), western blot (WB) and immunocytochemistry (ICC) analyses., Results: Histology confirmed the growth of SMCs in the hydrogel matrices. The myogenic growth factors decreased the proliferation rate of EnSCs, but they differentiated the human EnSCs into SMCs more efficiently on hydrogel matrices and expressed specific SMC markers including α-smooth muscle actin, desmin, vinculin and calponin in RT-PCR, WB and ICC experiments. The survival rate of cultures on the hydrogel-coated matrices was significantly higher than uncoated cultures., Conclusions: Human EnSCs were successfully differentiated into SMCs, using hydrogels as scaffold. EnSCs may be used for autologous bladder wall regeneration without any immunological complications in women. Currently work is in progress using bioabsorbable nanocomposite materials as EnSC scaffolds for developing urinary bladder wall tissue., (© 2013 The Authors. BJU International © 2013 BJU International.)

Research groups are currently recognising a critical clinical need for innovative approaches to organ failure and agenesis. Allografting, autologous reconstruction and prosthetics are hampered with severe limitations. Pertinently, readily available 'laboratory-grown' organs and implants are becoming a reality. Tissue engineering constructs vary in their design complexity depending on the specific structural and functional demands. Expeditious methods on integrating autologous stem cells onto nanoarchitectured 3D nanocomposites, are being transferred from lab to patients with a number of successful first-in-man experiences. Despite the need for a complete understanding of cell/material interactions tissue engineering is offering a plethora of exciting possibilities in regenerative medicine., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Aim: This study aimed to live monitor the degree of endothelial progenitor cell (EPC) integration onto tissue-engineering scaffolds by conjugating relevant antibodies to quantum dots (QDs)., Materials & Methods: Biocompatible mercaptosuccinic acid-coated QDs were functionalized with two different antibodies to EPC (CD133 with QDs of 640 nm wavelength [λ] and later-stage mature EPCs; and von Willebrand factor with QDs of λ595 and λ555 nm) using conventional carbomide and N-hydroxysuccinimide chemistry. Biofunctionalization was characterized with Fourier-transform infrared spectroscopy. Cell viability assays and gross morphology observations confirmed cytocompatibility and normal patterns of celluar growth. The antigens corresponding to each state of cell maturation were determined using a single excitation at λ488 nm., Results: The optimal concentrations of antibody-QD conjugates were biocompatible, hemocompatible and determined the state of EPC transformation to endothelial cells., Conclusion: Antibody-functionalized QDs suggest new applications in tissue engineering of polymer-based implants where cell integration can potentially be monitored without requiring the sacrifice of implants.

Human peripheral blood (HPB) contains both circulating endothelial cells (CECs) and endothelial progenitor stem cells (EPCs), which may be suitable for use in regenerative medicine. There has been considerable interest in using these cells, but there is no "gold standard" technique for isolating these cells. The aim of this study was to characterize and compare a number of different extraction and culture techniques to develop a system to isolate and culture cells. EPC and CEC were isolated from HPB using either Histopaque-1077 or Lymphoprep. The two isolation methods were compared for the number of cells isolated, cell metabolism, and RNA expression. Both isolations produced viable cells and were comparable. The tissue culture method employed does have a significant effect on the cell population with regard to medium choice, fetal bovine serum concentration, and surface modification of the culture surface. In conclusion, it can be seen that although this study and previous work can suggest a basis for culture, further work to develop an optimized and agreed "gold standard" culture regime for EPC from HPB is required to maximize the potential of this source of cells for regenerative medicine and to translate its clinical use in the future., (Copyright © 2011 International Union of Biochemistry and Molecular Biology, Inc.)

Owing to their noninvasive nature, coronary artery stents have become popular demand for patients undergoing percutaneous coronary intervention. Late restenosis, in-stent restenosis, and late thrombosis, all mediated by the denuded endothelium, represent the most recurrent failures of vascular stent induction. Higher patency rates of stents can be achieved by restoring the native internal environment of the vessel-an endothelium monolayer. This active organ inhibits the inflammatory reaction to injury responsible for thrombus and intimal hyperplasia, thereby providing a novel therapeutic option to combat the unacceptably high prevalence of restenosis. As the climax of the nanotechnology era approaches, tissue engineering is being explored by means of exploiting the multipotent abilities of stem cells and their adherence to bioactive surface nanocomposite polymers. The endothelium can be reconstructed from neighboring intact endothelium and adherence of circulating endothelium progenitor cells. The latter takes place via a series of signaling events: mobilization, adhesion, chemoattraction, migration, proliferation, and finally their differentiation in mature endothelial cells. A nanotopography surface can orchestrate endothelium formation, attributable to cellular interactions promoted by its nanosize. This review encompasses the prospect of in situ endothelialization, the mechanisms regulating the process, and the advantages of using a new generation of bioactive nanocomposite materials for coating metal stent scaffolds., (Copyright © 2011 International Union of Biochemistry and Molecular Biology, Inc.)

Stem cell therapy heralds a new chapter in cardiovascular regenerative medicine. Cardiovascular implants are often used in both surgery and interventional cardiology. Cardiovascular stents are utilized in percutaneous coronary interventions (PCI), and are classified as either bare metal stents (BMS) or drug-eluting stents (DES). Although DES might decrease the risk of vascular restenosis, there are complications (e.g. thrombosis) associated with it as well. Many new and novel composite materials are increasingly being developed along the premise of mobilizing and attracting endogenous stem cells to home-in and differentiate into a confluent layer of endothelial cell around the vessel wall. One of the main forces acting on cells in a blood vessel wall is fluid shear stress. Fluid shear stress is vital in establishing the vasculature of the embryo, and different shear stress patterns have been both implicated in maintaining vascular physiology, and also associated with certain pathological conditions. Recent evidence suggests that via a plethora of mechanosensors and mechanotransduction signaling pathways, stem cells differentiate into endothelial cells when exposed to fluid shear stress. Here we review the current knowledge pertaining to the roles that mechanosensors and mechanotransducers play in stem cell differentiation into endothelial cells via fluid shear stress, and its implications for pharmacological applications and cardiovascular implants in the realm of regenerative medicine.

The treatment of cartilage pathology and trauma face the challenges of poor regenerative potential and inferior repair. Nevertheless, recent advances in tissue engineering indicate that adult stem cells could provide a source of chondrocytes for tissue engineering that the isolation of mature chondrocytes has failed to achieve. Various adjuncts to their propagation and differentiation have been explored, such as biomaterials, bioreactors and growth hormones. To date, all tissue engineered cartilage has been significantly mechanically inferior to its natural counterparts and further problems in vivo relate to poor integration and deterioration of tissue quality over time. However, adult stem cells--with their high rate of proliferation and ease of isolation--are expected to greatly further the development and usefulness of tissue engineered cartilage.

Atherosclerosis and heart disease are still the leading causes of morbidity and mortality worldwide. The lack of suitable autologous grafts has produced a need for artificial grafts but the patency of such grafts is limited compared to natural materials. Tissue engineering, whereby living tissue replacements can be constructed, has emerged as a solution to some of these difficulties. This, in turn, is limited by the availability of suitable cells from which to construct the vessels. The development of prosthesis using progenitor cells and switching these into endothelial cells is an important and exciting advance in the field of tissue engineering. Here, we describe recent developments in the use of stem cells for the development of replacement vessels. These paradigm shifts in vascular engineering now offer a new route for effective clinical therapy.

The apparent difficulty to precisely control fine-tuning of biomaterial degradation has initiated the recent paradigm shift from conventional top-down fabrication methods to more nature-inspired bottom-up assemblies. Sophistication of material fabrication techniques allows today's scientists to reach beyond conventional natural materials in order to synthesise tomorrow's 'designer material'. Material degradation into smaller components and subsequent release of encapsulated cells or cell-signalling agents have opened medically exploitable avenues, transforming the area of regenerative medicine into a dynamic and self-propagating branch of modern medicine. The aim to synthesise ever more refined scaffolding structures in order to create micro- and nanoenvironments resembling those found in natural tissues now represents an ever growing niche in the materials sciences. Recently, we have developed and conducted the world's first in-human tracheal transplantation using a non-degradable completely synthetic biomaterial. Fuelled by such clinical potential, we are currently developing a biodegradable version suitable for skin tissue engineering and paediatric applications. However, despite enormous efforts, current, as yet insurmountable challenges include precise biomaterial degradation within pre-determined spatial and temporal confines in an effort to release bio-signalling agents in such orchestrated fashion as to fully regenerate functioning tissues. In this review, the authors, almost anti-climactically, ask the readers to step out of the artificially over-constructed spiral of ever more convoluted scaffold fabrication techniques and consider the benefits of controllable bottom-up scaffold fabrication methods. It will further be investigated how scaffold designs and fabrication methods may influence degradation and subsequent release of incorporated elements. A focus will be placed on the delivery of growth factors, stem cells and therapeutic agents alone or in parallel. The difficulties of designing a delivery vehicle capable of delivering multiple factors whilst maintaining distinct release kinetics will be highlighted. Finally, this review will be rounded off with an insight into current literature addressing the recurring issues of degradation product toxicities and suggests means of overcoming those. [ABSTRACT FROM AUTHOR]

Abstract: Scaffold cellularization for cartilage engineering can aid implant properties, their retention and minimize repeated intervention, particularly in paediatric reconstructive craniofacial surgery. We developed novel bionanoscaffolds using paediatric adipose tissue-derived stem cells (hADSCs), an accessible autologous cell source, and POSS-PCU. Little is known about cellular responses to this nanomaterial, though it was used in human. We assessed: 1) POSS-PCU cellularization and bioaffinity to hADSCs; 2) hADSC chondrogenic differentiation ability in POSS-PCU; 3) whether bionanoscaffolds became encased within a vascular network and/or vascularised. POSS-PCU supported ADSC survival and proliferation and their migration and differentiation into cartilage within the nanoscaffold. Furthermore, after CAM-grafting, bionanoscaffolds were rapidly surrounded by blood vessels without any apparent negative reaction and erythrocytes of host origin were detected inside the scaffold, suggesting invasion from some capillaries. Altogether, this study demonstrates that POSS-PCU displays excellent bioactivity and hADSC/POSS-PCU bionanoscaffolds offer much promise for autologous cell-based tissue engineering for clinical applications. From the Clinical Editor: In this study, human adipose tissue derived stem cells were used in combination with POSS-PCU nanoscaffolds to generate cartilage tissue demonstrating excellent bioactivity for autologous cell-based tissue engineering for clinical applications. [Copyright &y& Elsevier]

Aims The aim of this study was the safety assessment of urethra injections of autologous total nucleated cells (TNCs) along with platelets, which focused on the outcome over a 6 month period. Methods An open, prospective study was conducted on 9 patients with severe stress urinary incontinence (SUI). At the baseline, 1, 3, and 6 months after external urethral sphincteric and submucosal injections of autologous TNCs along with platelets, the patients were assessed according to cough tests, Q-Tip tests, urodynamics, 1 hr pad tests, upper tract ultrasonography (UTU), post voiding residue (PVR), International Consultation on Incontinence Questionnaire-Urinary incontinence (ICIQ-UI), and International Consultation on Incontinence Modular Questionnaire-Quality of Life (ICIQ-QOL). On the 3rd month post-injection, the maximum urethral closure pressure (MUCP) and abdominal leak point pressure (ALPP) were measured in one patient with intrinsic sphincteric deficiency (ISD; the baseline: ALPP < 60 and MUCP < 30 cmH2O). Results No complications were observed after injection. At 6-months' follow up (F/U), all the patients considered themselves clinically cured with eight women completely continent and one marked improvement. Mean age was 48.9 ± 13.8 years. Before the injection, urodynamics, UTU, and PVR were normal and cough tests, 1 hr pad tests were positive in patients. At 1, 3, and 6 months post-injection, there was a significant improvement in ICIQ-UI, ICIQ-QOL ( P < 0.05). UTU and PVR were normal, cough tests, and 1 hr pad tests were negative, except for ISD patient with severe coughs (at month 3: ALPP = 92 and MUCP > 30 cmH2O). Conclusion Cell therapy consisting of intrasphincteric and submucosal injections of autologous TNCs along with platelets in SUI patients is a feasible and safe procedure. The results point out those subjects cured or with marked improvement after 6 months F/U. Neurourol. Urodynam. 32: 377-382, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Reconstruction of the human auricle remains a challenge to plastic surgeons, and current approaches are not ideal. Tissue engineering provides a promising alternative. This study aims to evaluate the chondrogenic potential of bone marrow-derived mesenchymal stem cells on a novel, auricular-shaped polymer. The proposed polyhedral oligomeric silsesquioxane-modified poly(hexanolactone/carbonate)urethane/urea nanocomposite polymer has already been transplanted in patients as the world's first synthetic trachea, tear duct and vascular bypass graft. The nanocomposite scaffold was fabricated via a coagulation/salt-leaching method and shaped into an auricle. Adult bone marrow-derived mesenchymal stem cells were isolated, cultured and seeded onto the scaffold. On day 21, samples were sent for scanning electron microscopy, histology and immunofluorescence to assess for neocartilage formation. Cell viability assay confirmed cytocompatability and normal patterns of cellular growth at 7, 14 and 21 days after culture. This study demonstrates the potential of a novel polyhedral oligomeric silsesquioxane-modified poly(hexanolactone/carbonate)urethane/urea scaffold for culturing bone marrow-derived mesenchymal stem cells in chondrogenic medium to produce an auricular-shaped construct. This is supported by scanning electron microscopy, histological and immunofluorescence analysis revealing markers of chondrogenesis including collagen type II, SOX-9, glycosaminoglycan and elastin. To the best of our knowledge, this is the first report of stem cell application on an auricular-shaped scaffold for tissue engineering purposes. Although many obstacles remain in producing a functional auricle, this is a promising step forward. [ABSTRACT FROM AUTHOR]

Summary: Introduction: The associated morbidity from the acquisition of mesenchymal stem cells (MSC) from the bone marrow has led to the investigation of alternative stem cell sources. We propose that such cells may be isolated from non-mobilised blood and demonstrate their differentiation into a chondrocytic lineage. This safe and abundant source of cells may be useful for tissue engineering cartilage. Method: Peripheral blood mononuclear cells (PBMC) were isolated from healthy adults and cultured in RPMI medium supplemented with serum. The non-adherent and adherent cells were analysed for cell surface marker expression of CD14, CD34, CD133, CD105 and CD45 by flow cytometry. Adherent cells were also cultured on glass slides in chondrogenic media and analysed for the expression of collagen I and II on day 14 of culture. Results: The adherent cells were fibroblastic in morphology and were confluent on day 14. The non-adherent and adherent cell populations were shown to have distinct profiles by flow cytometry. The adherent cells were positive for CD105 and CD14 and also expressed collagen I and II precursors when cultured in chondrogenic media. Conclusion: Blood-acquired mesenchymal progenitor cells (BMPCs) can be isolated from non-mobilised blood. These unique cells are CD105+ and CD14+ and have chondrogenic differentiation capacity. BMPC may provide a potential source of MPC for tissue engineering applications. [Copyright &y& Elsevier]

The multiple demands placed on small calibre cardiovascular bypass grafts have meant that a synthetic prosthesis with good long-term patency has not been developed. A tissue-engineered graft could fulfil the ideal characteristics present in an artery. However, the great disadvantage of such a conduit is the time necessary for maturation leading to unacceptable delays once the decision to intervene surgically has been made. This maturation process is essential to produce a graft which can withstand haemodynamic stress. Once implanted, the tissue-engineered graft can contract in response to immediate haemodynamic conditions and remodel in the long term. We review the latest tissue engineering approaches used to give the favourable properties of mechanical strength, arterial compliance, low thrombogenicity, long-term resistance towards biodegradation as well as technological advances which shorten the time required for production of an implantable graft. [ABSTRACT FROM AUTHOR]

Desirable carbon allotropes such as graphene oxide (GO) have entered the field with several biomedical applications, owing to their exceptional physicochemical and biological features, including extreme strength, found to be 200 times stronger than steel; remarkable light weight; large surface-to-volume ratio; chemical stability; unparalleled thermal and electrical conductivity; and enhanced cell adhesion, proliferation, and differentiation properties. The presence of functional groups on graphene oxide (GO) enhances further interactions with other molecules. Therefore, recent studies have focused on GO-based materials (GOBMs) rather than graphene. The aim of this research was to highlight the physicochemical and biological properties of GOBMs, especially their significance to biomedical applications. The latest studies of GOBMs in biomedical applications are critically reviewed, and in vitro and preclinical studies are assessed. Furthermore, the challenges likely to be faced and prospective future potential are addressed. GOBMs, a high potential emerging material, will dominate the materials of choice in the repair and development of human organs and medical devices. There is already great interest among academics as well as in pharmaceutical and biomedical industries. [ABSTRACT FROM AUTHOR]

Spinal cord injury is a chronic and debilitating neurological condition that is currently being managed symptomatically with no real therapeutic strategies available. Even though there is no consensus on the best time to start interventions, the chronic phase is definitely the most stable target in order to determine whether a therapy can effectively restore neurological function. The advancements of nanoscience and stem cell technology, combined with the powerful, novel neuroimaging modalities that have arisen can now accelerate the path of promising novel therapeutic strategies from bench to bedside. Several types of stem cells have reached up to clinical trials phase II, including adult neural stem cells, human spinal cord stem cells, olfactory ensheathing cells, autologous Schwann cells, umbilical cord blood-derived mononuclear cells, adult mesenchymal cells, and autologous bone-marrow-derived stem cells. There also have been combinations of different molecular therapies; these have been either alone or combined with supportive scaffolds with nanostructures to facilitate favorable cell–material interactions. The results already show promise but it will take some coordinated actions in order to develop a proper step-by-step approach to solve impactful problems with neural repair. [ABSTRACT FROM AUTHOR]

Skin wounds are a major social and financial burden. However, current treatments are suboptimal. The gradual comprehension of the finely orchestrated nature of intercellular communication has stimulated scientists to investigate growth factor (GF) or stem cell (SC) incorporation into suitable scaffolds for local delivery into wound beds in an attempt to accelerate healing. This review provides a critical evaluation of the status quo of current research into GF and SC therapy and subsequent future prospects, including benefits and possible long-term dangers associated with their use. Additionally, we stress the importance of a bottom-up approach in scaffold fabrication to enable controlled factor incorporation as well as production of complex scaffold micro- and nanostructures resembling that of natural extracellular matrix. [ABSTRACT FROM AUTHOR]

There have been many attempts to provide sufficient nutrients, especially oxygen, to engineered large tissues to overcome the effects of hypoxia or poor vascularization. Delivering sufficient oxygen to the transplanted cells is one of the most critical issues that affects cell survival and correct maturation of engineered tissues. An emerging approach is using 3D scaffolds made from oxygen-generating biomaterials to tackle transport limitations deep within the engineered tissues. This class of biomaterials has opened a new window for overcoming the challenges associated with ischemia occurring within large tissue constructs. This review critically assesses oxygen-generating reagents, the main approaches for developing oxygen-generating biomaterials, and their potential as 3D scaffolds for regenerative medicine in a clinical setting. [ABSTRACT FROM AUTHOR]

Abstract: Background: Although commercial skin substitutes are widely available, its use remains challenging at surgery and postoperatively. The high cost is also prohibitive. We designed and characterized a scaffold for dermal replacement, using advanced nanocomposite materials, which are known to have unique nanoscale features that enhance cellular behavior. Methods: A bilayered scaffold was developed using the nanocomposite, polyhedral oligomeric silsesquioxane, incorporated into poly(caprolactone-urea)urethane, resulting in a mechanically robust bioabsorbable polymer; forming the inner layer, which was designed with a range of porosities. The removable outer layer contained nanosilver. Tensile testing, surface tension, permeability, and scanning electron microscopy were performed. Optimal pore morphology for cellular proliferation was elucidated through adipose tissue–derived stem cell culture and a cell viability assay. All tests were repeated on Integra Dermal Regeneration Template. Results: The physical construct was easy to handle and clinically applicable. Macroporosity and permeability of scaffolds was demonstrated, confirmed by scanning electron microscopy. Both tensile strength and surface tension were comparable with skin; outer layer demonstrated hydrophobicity and inner layer showed hydrophilicity. Cell assay confirmed cellular proliferation onto the scaffold, comparable with Integra. Conclusions: We demonstrate that a porous bilayered dermal scaffold could form the basis of a new generation of skin substitute that is both mechanically robust and harbors the ability for enhancing cell regeneration. [Copyright &y& Elsevier]