| |  | | | | | | | | | | | | | | | |  | | | | | | | | | | | | | | | | | | | | | | | | A new approach to heart valve tissue engineering: mimicking the heart ventricle with a ventricular assist device in a novel bioreactor. J Tissue Eng Regen Med. 2010 Aug 4; Authors: Kaasi A, Cestari IA, Stolf NA, Leirner AA, Hassager O, Cestari IN The 'biomimetic' approach to tissue engineering usually involves the use of a bioreactor mimicking physiological parameters whilst supplying nutrients to the developing tissue. Here we present a new heart valve bioreactor, having as its centrepiece a ventricular assist device (VAD), which exposes the cell-scaffold constructs to a wider array of mechanical forces. The pump of the VAD has two chambers: a blood and a pneumatic chamber, separated by an elastic membrane. Pulsatile air-pressure is generated by a piston-type actuator and delivered to the pneumatic chamber, ejecting the fluid in the blood chamber. Subsequently, applied vacuum to the pneumatic chamber causes the blood chamber to fill. A mechanical heart valve was placed in the VAD's inflow position. The tissue engineered (TE) valve was placed in the outflow position. The VAD was coupled in series with a Windkessel compliance chamber, variable throttle and reservoir, connected by silicone tubings. The reservoir sat on an elevated platform, allowing adjustment of ventricular preload between 0 and 11 mmHg. To allow for sterile gaseous exchange between the circuit interior and exterior, a 0.2 microm filter was placed at the reservoir. Pressure and flow were registered downstream of the TE valve. The circuit was filled with culture medium and fitted in a standard 5% CO(2) incubator set at 37 degrees C. Pressure and flow waveforms were similar to those obtained under physiological conditions for the pulmonary circulation. The 'cardiomimetic' approach presented here represents a new perspective to conventional biomimetic approaches in TE, with potential advantages. Copyright (c) 2010 John Wiley & Sons, Ltd. PMID: 20687125 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Progenitor-derived endothelial cell response, platelet reactivity and haemocompatibility parameters indicate the potential of NaOH-treated polycaprolactone for vascular tissue engineering. J Tissue Eng Regen Med. 2010 Aug 4; Authors: Serrano MC, Pagani R, Peña J, Vallet-Regà M, Comas JV, Portolés MT The haemocompatibility of NaOH-treated poly(epsilon-caprolactone) (PCL) has been evaluated in vitro by analysing several parameters, including plasma recalcification time, whole blood clotting time and platelet adhesion/activation. NaOH-treated PCL films showed a significant decrease in the clot formation speed and a reduced number of adhered platelets, which mainly exhibited non-activated morphologies. Furthermore, mature endothelial cells derived from peripheral endothelial progenitor cells were cultured on the polymer to investigate the effects of the endothelial lining on polymer haemocompatibility. Interestingly, cells cultured on NaOH-treated PCL films showed a significant stimulation of NO production. Although further research is required, NaOH treatment could be an interesting and simple strategy to modify PCL-based materials in order to enhance endothelial NO production, where compromised, and provide a better interaction of the scaffold with the blood components. In conclusion, these results reinforce the use of NaOH-treated PCL as a haemocompatible polymer for vascular tissue-engineering applications. Copyright (c) 2010 John Wiley & Sons, Ltd. PMID: 20687124 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Dermal fibroblast behaviour on micropatterned substrates with different pattern geometries. J Tissue Eng Regen Med. 2010 Aug 3; Authors: Jiang Y, Lu S, Zeng Y A major objective of scaffold fabrication for tissue-engineering applications in wound healing is to understand the relationship between scaffold topography and cell behaviour. Recently, researchers have focused on arrays of cell adhesion protein styled in linear-grid micropatterns; however, these linear-grid patterns hardly reflect the topographical features of a natural extracellular matrix (ECM). In order to clarify the relationship between substrate adhesion points and cell behaviour, changes of dermal fibroblasts cultured on triangular microdot arrays were investigated. Micropatterns were micro-printed by silicone substrate stamps with collagen, while regions outside of the microdots were functionalized to block cellular adhesion. Cell morphology, expression of alpha-SMA, cell viability and hydroxyproline levels were examined for dermal fibroblasts cultured on the microdot substrates and on non-patterned control substrates. On patterned substrates, the expression of alpha-SMA significantly decreased, cell vitality increased and hydroxyproline content decreased with increasing vertex angles of the triangular array. Significantly more hydroxyproline was observed in all experimental groups in comparison to the control group. The results indicate that small vertex angles of the triangular array were detrimental to cell survival, likely due to constraint of the cell to a small adhesion area. We hypothesize that cells actively adapt to this situation by attempting to remodel their microenvironments with secretion of hydroxyproline. This illustrates the existence of feedback between cells and their microenvironments, such that when surroundings are unfavourably altered, the cells attempt to reconstruct the environment with secretion of ECM. Copyright (c) 2010 John Wiley & Sons, Ltd. PMID: 20687049 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | alpha5beta1 Integrin-Fibronectin Interactions Specify Liquid to Solid Phase Transition of 3D Cellular Aggregates. PLoS One. 2010;5(7):e11830 Authors: Caicedo-Carvajal CE, Shinbrot T, Foty RA BACKGROUND: Tissue organization during embryonic development and wound healing depends on the ability of cells on the one hand to exchange adhesive bonds during active rearrangement and on the other to become fixed in place as tissue homeostasis is reached. Cells achieve these contradictory tasks by regulating either cell-cell adhesive bonds, mediated by cadherins, or cell-extracellular matrix (ECM) connections, regulated by integrins. Integrin alpha5beta1 and soluble fibronectin (sFN) are key players in cell-ECM force generation and in ECM polymerization. Here, we explore the interplay between integrin alpha5beta1 and sFN and its influence on tissue mechanical properties and cell sorting behavior. METHODOLOGY/PRINCIPAL FINDINGS: We generated a series of cell lines varying in alpha5beta1 receptor density. We then systematically explored the effects of different sFN concentrations on aggregate biomechanical properties using tissue surface tensiometry. We found previously unreported complex behaviors including the observation that interactions between fibronectin and integrin alpha5beta1 generates biphasic tissue cohesion profiles. Specifically, we show that at constant sFn concentration, aggregate cohesion increases linearly as alpha5beta1 receptor density is increased from low to moderate levels, producing a transition from viscoelastic-liquid to pseudo viscoelastic-solid behavior. However, further increase in receptor density causes an abrupt drop in tissue cohesion and a transition back to viscoelastic-liquid properties. We propose that this may be due to depletion of sFn below a critical value in the aggregate microenvironment at high alpha5beta1 levels. We also show that differential expression of alpha5beta1 integrin can promote phase-separation between cells. CONCLUSIONS/SIGNIFICANCE: The interplay between alpha5-integrin and sFn contributes significantly to tissue cohesion and, depending on their level of expression, can mediate a shift from liquid to elastic behavior. This interplay represents a tunable level of control between integrins and the ECM that can influence tissue cohesion and other mechanical properties, which may translate to the specification of tissue structure and function. These studies provide insights into important biological processes such as embryonic development, wound healing, and for tissue engineering applications. PMID: 20686611 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Interaction and self-organization of human mesenchymal stem cells and neuro-blastoma SH-SY5Y cells under co-culture conditions: a novel system for modeling cancer cell micro-environment. Eur J Pharm Biopharm. 2010 Jun 1; Authors: Rizvanov AA, Yalvaç ME, Shafigullina AK, Salafutdinov II, Blatt NL, Sahin F, Kiyasov AP, Palotás A The common drawback of many in vitro cell culture systems is the absence of appropriate micro-environment, which is formed by the combination of factors such as cell-cell contacts, extra-cellular matrix and paracrine regulation. Micro-environmental factors in a tumor tissue can influence physiological status of the cancer cells and their susceptibility to anti-cancer therapies. Interaction of cancer cells with their micro-environment and regional stem cells, therefore, is of particular interest. Development of in vitro systems which allow more accurate modeling of complex relations occurring in real tumor environments can increase efficiency of preclinical assays for screening anti-cancer drugs. The aim of this work was to study interactions between human mesenchymal stem cells (MSCs) and neuro-blastoma cancer SH-SY5Y cells under co-culture conditions on different coated surfaces to determine the effect of co-existence of cancer and stem cells on each cellular population under various stress conditions. We developed an efficient in vitro system for studying individual cancer and stem cell populations during co-culture using differential live fluorescent membrane labeling, and demonstrated self-organization of cancer and stem cells during co-culture on various coated surfaces. Our findings support the evidence that cancer and stem cell interactions play important roles in cellular behavior of cancer cells. These properties can be used in different fields of cancer research, tissue engineering and biotechnology. PMID: 20685331 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Human eccrine sweat gland cells can reconstitute a stratified epidermis. J Invest Dermatol. 2010 Aug;130(8):1996-2009 Authors: Biedermann T, Pontiggia L, Böttcher-Haberzeth S, Tharakan S, Braziulis E, Schiestl C, Meuli M, Reichmann E Eccrine sweat glands are generally considered to be a possible epidermal stem cell source. Here we compared the multilayered epithelia formed by epidermal keratinocytes and those formed by eccrine sweat gland cells. We demonstrated both in vitro and in vivo the capability of human eccrine sweat gland cells to form a stratified interfollicular epidermis substitute on collagen hydrogels. This is substantiated by the following findings: (1) a stratified epidermis consisting of 10-12 cell layers is formed by sweat gland cells; (2) a distinct stratum corneum develops and is maintained after transplantation onto immuno-incompetent rats; (3) proteins such as filaggrin, loricrin, involucrin, envoplakin, periplakin, and transglutaminases I and III match with the pattern of the normal human skin; (4) junctional complexes and hemidesmosomes are readily and regularly established; (5) cell proliferation in the basal layer reaches homeostatic levels; (6) the sweat gland-derived epidermis is anchored by hemidesmosomes within a well-developed basal lamina; and (7) palmo-plantar or mucosal markers are not expressed in the sweat gland-derived epidermis. These data suggest that human eccrine sweat glands are an additional source of keratinocytes that can generate a stratified epidermis. Our findings raise the question of the extent to which the human skin is repaired and/or permanently renewed by eccrine sweat gland cells. PMID: 20376062 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Selection, enrichment, and maintenance of self-renewal liver stem/progenitor cells utilizing polypeptide polyelectrolyte multilayer films. Biomacromolecules. 2010 Apr 12;11(4):994-1001 Authors: Tsai HA, Wu RR, Lee IC, Chang HY, Shen CN, Chang YC Recent progress has led to the identification of liver stem/progenitor cells as suitable sources for generating transplantable liver cells. However, the great variability in methods utilized to isolate liver stem/progenitor cells is a considerable challenge for clinical applications. The polyelectrolyte-multilayer technique can constitute a useful method for selective cell adhesion. Whether enrichment of liver stem/progenitor cells can be achieved utilizing polypeptide polyelectrolyte-multilayer films was investigated in current work. Fetal liver cells isolated from E13.5 mouse embryos were seeded on the poly-l-glutamic acid/poly-l-lysine alternating films, and we revealed that fetal liver stem/progenitor cells were selected and formed colonies. These undifferentiated colonies were maintained on the films composed of four alternating layers, with the topmost poly-l-glutamic acid layer judged by the constitutive expression of stem-cell markers such as Dlk-1, CD49f, and CD133 and self-renew marker-beta-catenin. Our work has demonstrated that highly tunable polyelectrolyte-multilayer films were suitable for selective enrichment of liver stem/progenitor cells in vitro. PMID: 20337459 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Effects of introducing cultured human chondrocytes into a human articular cartilage explant model. Cell Tissue Res. 2010 Feb;339(2):421-7 Authors: Secretan C, Bagnall KM, Jomha NM Articular cartilage (AC) heals poorly and effective host-tissue integration after reconstruction is a concern. We have investigated the ability of implanted chondrocytes to attach at the site of injury and to be incorporated into the decellularized host matrix adjacent to a defect in an in vitro human explant model. Human osteochondral dowels received a standardized injury, were seeded with passage 3 chondrocytes labelled with PKH 26 and compared with two control groups. All dowels were cultured in vitro, harvested at 0, 7, 14 and 28 days and assessed for chondrocyte adherence and migration into the region of decellularized tissue adjacent to the defects. Additional evaluation included cell viability, general morphology and collagen II production. Seeded chondrocytes adhered to the standardized defect and areas of lamina splendens disruption but did not migrate into the adjacent acellular region. A difference was noted in viable-cell density between the experimental group and one control group. A thin lattice-like network of matrix surrounded the seeded chondrocytes and collagen II was present. The results indicate that cultured human chondrocytes do indeed adhere to regions of AC matrix injury but do not migrate into the host tissue, despite the presence of viable cells. This human explant model is thus an effective tool for studying the interaction of implanted cells and host tissue. PMID: 20012649 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | [Clinical application of acellular dermal matrix to prevent gustatory sweating syndrome] Zhonghua Kou Qiang Yi Xue Za Zhi. 2007 Sep;42(9):570-1 Authors: Yu K, Yang J, Li MJ, Ma HB OBJECTIVE: To evaluate the clinical effect of acellular dermal matrix (ADM) on preventing Frey syndrome after parotidectomy. METHODS: Fifty-seven patients were randomized into two groups, ADM group (30 patients) receiving acellular dermal matrix and control group (27 patients) without application of acellular dermal matrix. The incidence of Frey syndrome was evaluated after operation. RESULTS: The incidences of Frey syndrome were 13.3% in ADM group and 55.6% in control group. There was significant difference in Frey syndrome incidence between the two groups (P < 0.01). CONCLUSIONS: The application of acellular dermal matrix could effectively prevent Frey syndrome after parotidectomy. PMID: 18070440 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | In vitro cardiomyogenic potential of human amniotic fluid stem cells. J Tissue Eng Regen Med. 2010 Aug 4; Authors: Guan X, Delo DM, Atala A, Soker S Stem cell therapy for damaged cardiac tissue is currently limited by a number of factors, including inability to obtain sufficient cell numbers, the potential tumorigenicity of certain types of stem cells and the possible link between stem cell therapy and the development of malignant arrhythmias. In this study, we investigated whether human amniotic fluid-derived stem (hAFS) cells could be a potential source of cells for cardiac cell therapy, by testing the in vitro differentiation capabilities. Undifferentiated hAFS cells express several cardiac genes, including the transcription factor mef2, the gap junction connexin43, and H- and N-cadherin. A 24 h incubation with 5-aza-2'-deoxycytidine (5-AZA-dC) induced hAFS cell differentiation along the cardiac lineage. Evidence for this differentiation included morphological changes, upregulation of cardiac-specific genes (cardiac troponin I and cardiac troponin T) and redistribution of connexin43, as well as downregulation of the stem cell marker SRY-box 2 (sox2). When co-cultured with neonatal rat cardiomyocytes (NRCs), hAFS cells formed both mechanical and electrical connections with the NRCs. Dye transfer experiments showed that calcein dye could be transferred from NRCs to hAFS cells through cellular connections. The gap junction connexin43 likely involved in the communication between the two cell types, because 12-O-tetradecanoylphorbol 13-acetate (TPA) could partially block cellular crosstalk. We conclude that hAFS cells can be differentiated into a cardiomyocyte-like phenotype and can establish functional communication with NRCs. Thus, hAFS cells may potentially be used for cardiac cell therapy. Copyright (c) 2010 John Wiley & Sons, Ltd. PMID: 20687122 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Assessing In Vivo MicroRNA Function in the Germline Stem Cells of the Drosophila Ovary. Methods Mol Biol. 2010;650:201-12 Authors: Chan K, Ruohola-Baker H A more complete understanding of the biology of adult stem cells could yield important insights toward devising effective cell-based regenerative therapies to treat disease. The germline stem cells (GSCs) in the fruit fly Drosophila melanogaster are an excellent in vivo model for the study of adult stem cell biology. There is increasing evidence from a growing field that microRNAs (miRNAs) play important roles in controlling many aspects of stem-cell biology. Using straightforward genetic manipulations combined with well-established cell biological analysis techniques, we and others have found that the miRNA pathway regulates the cell division rate of Drosophila GSCs as well as the maintenance of the GSCs in their niche. In this chapter, we offer a detailed, self-contained description of a general method to assess the in vivo functions of miRNAs in the GSCs of the Drosophila ovary. PMID: 20686953 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | An efficient transfection method for mouse embryonic stem cells. Methods Mol Biol. 2010;650:145-53 Authors: Liou JY, Ko BS, Chang TC Embryonic stem (ES) cells are an important source of stem cells in tissue engineering and regenerative medicine because of their high self-renewal capacities and differentiation potentials. However, the detailed molecular mechanisms controlling the differentiation and renewal programs in ES cells remained unclear. One of the difficulties in understanding these mechanisms substantially results from the low efficacies of gene manipulation by delivering exogenous gene expression or knockdown of endogenous gene expression with small interfering RNA (siRNA) in ES cells. Here we describe an optimized protocol for efficiently transfecting mouse ES cells by Effectene, a liposome-based method. The high transfection efficiency in mouse ES cells is demonstrated in this chapter by (1) achieving a percentage of enhanced green fluorescence protein (EGFP) expression in >98% embryoid bodies after introducing plasmids encoding the protein and (2) decreased SOX-2 and Oct-3/4 expression and subsequent morphological evidence of cell differentiation after introducing siRNA expression for suppressing SOX-2 and Oct-3/4, which are known to be essential for maintenance of stem cell properties in mouse ES cells. PMID: 20686950 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Investigation of bone allografts representing different steps of the bone bank procedure using the CAM-model. ALTEX. 2010;27(2):97-103 Authors: Holzmann P, Niculescu-Morzsa E, Zwickl H, Halbwirth F, Pichler M, Matzner M, Gottsauner-Wolf F, Nehrer S Bone grafting is commonly used to treat large bone defects. Since autografts are limited and frequently associated with postoperative donor morbidity, allografts from bone banks are often used. However, vascularisation of the allograft is often impaired, resulting in inadequate bone healing and functional graft failure. In bone bank processing, tissue is stored at -80 degree Celsius and subsequently subjected to a harsh multi-step cleaning and sterilisation procedure to prevent immune rejection or transmission of diseases. To determine which step of this procedure diminishes the ability of allografts to induce or promote vascularisation, we used the chick chorioallantoic membrane (CAM) model to monitor the vascular reaction to sample bone chips representing the respective procedural steps. The CAM model monitors the angiogenic potency of xenogeneic and, hence, potentially immunogeneic materials (e.g. cells, tissues, tissue-engineered matrices). Due to the chicken embryo's lack of a fully functional immune system, it provides test conditions that are analogous to immunologically incompetent mice and is a well-suited alternative to their use. Bone chips were placed onto the CAM, and vascular reactions were quantified by image analysis after 48 h incubation. The vascular reaction was most pronounced to fresh, untreated bone chips that had been kept at +2 degree Celsius prior to the experiment. Surprisingly, storage of bone samples at -80 degree Celsius was sufficient to drastically reduce the vascular reaction. Consistent with this, samples representing different stages of the subsequent procedure showed similarly low vascular indices. PMID: 20686742 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Boron regulates mineralized tissue-associated proteins in osteoblasts (MC3T3-E1). J Trace Elem Med Biol. 2010 Aug 2; Authors: Hakki SS, Bozkurt BS, Hakki EE The aim of this study was to determine the effects of boron (B) on the cell-survival, proliferation, mineralization and mRNA expression of mineralized tissue-associated proteins. Additionally, determination of the effects of B on the BMP-4, -6 and -7 protein levels of pre-osteoblastic cells (MC3T3-E1) was also intended. The effects of B (pH 7.0) concentrations (0, 0.1, 1, 10, 100, 1000, 2000, 4000, 8000 and 10,000ng/ml) on the survival of the cells were evaluated at 24 and 96hrs with MTT assay. To evaluate the proliferation in long term, MC3T3-E1 cells were treated with different concentrations of B (0, 0.1, 1, 10, 100 and 1000ng/ml) and were counted on days 2, 5, and 14. While in short term, decreased cell survival rate was observed at 1000ng/ml and above, at long term no statistically significant difference was detected in different B concentrations applied. Slight decreases at the proliferation of the B-treated groups were determined on days 5 and 14 but one-way analysis of variance revealed that the difference was statistically insignificant. In mineralization assay, increased mineralized nodules were apparently observed in B treatment (1 and 10ng/ml concentrations) groups. Based on quantitative RT-PCR results, remarkable regulation in favor of osteoblastic function for Collagen type I (COL I), Osteopontin (OPN), Bone Sialoprotein (BSP), Osteocalcin (OCN) and RunX2 mRNA expressions were observed in B treatment groups in comparison with untreated control groups. Increased BMP-4, -6 and -7 protein levels were detected at 0.1, 1, 10 and 100ng/ml B concentrations. Results of the study suggest that at the molecular level B displays important roles on bone metabolism and may find novel usages at the regenerative medicine. PMID: 20685097 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | The effect of matrix characteristics on fibroblast proliferation in 3D gels. Biomaterials. 2010 Aug 2; Authors: Bott K, Upton Z, Schrobback K, Ehrbar M, Hubbell JA, Lutolf MP, Rizzi SC Engineering synthetic hydrogels on a molecular basis to introduce natural features that are important in instructing cell behavior is becoming increasingly crucial in biomaterial-based approaches for regenerative medicine and in cell biology to study cell-matrix interactions in three-dimensions (3D). Here, we used collagen gels and exploited the design flexibility of the biological, biochemical and physical characteristics offered by a PEG-based hydrogel system to systematically study the effect of specific extracellular microenvironments on the behavior of primary human fibroblasts in 3D. We firstly found that the proliferation profiles of fibroblasts from different patients cultured within collagen gels (3D) differed significantly from their behavior observed on tissue culture plastic (2D). Furthermore, using the biomimetic PEG-based matrix we showed that cell proliferation in 3D could be selectively manipulated via alteration of the gel characteristics. In particular, this study revealed that, in spite of matrix sensitivity to proteases (e.g. MMP) and the presence of cell-integrin binding sites, at high stiffness (elastic modulus, G' >1200 Pa) the matrix acts as a barrier for cells cultured in 3D. Finally, a comparison between the biomimetic PEG-based and collagen gels indicated that differences in their viscoelastic behaviours, determined by the nature of network structures and cross-links, may influence the mechanism(s) cells employ to remodel their 3D extracellular microenvironment. In conclusion, these studies highlight that for proliferation in 3D, compared to 2D, cells require strategies to overcome the physical impediment posed by the matrix. We also demonstrate that by exploiting the design flexibility of the characteristics offered by these biomimetic hydrogels, it is possible to separately investigate complex aspects characterizing the cell-matrix interactions in 3D; this has the potential to have great impact in regenerative medicine, as well as in cell biology and cancer research. PMID: 20684983 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Pericyte-based human tissue engineered vascular grafts. Biomaterials. 2010 Aug 2; Authors: He W, Nieponice A, Soletti L, Hong Y, Gharaibeh B, Crisan M, Usas A, Peault B, Huard J, Wagner WR, Vorp DA The success of small-diameter tissue engineered vascular grafts (TEVGs) greatly relies on an appropriate cell source and an efficient cellular delivery and carrier system. Pericytes have recently been shown to express mesenchymal stem cell features. Their relative availability and multipotentiality make them a promising candidate for TEVG applications. The objective of this study was to incorporate pericytes into a biodegradable scaffold rapidly, densely and efficiently, and to assess the efficacy of the pericyte-seeded scaffold in vivo. Bi-layered elastomeric poly(ester-urethane)urea scaffolds (length = 10 mm; inner diameter = 1.3 mm) were bulk seeded with 3 x 10(6) pericytes using a customized rotational vacuum seeding device in less than 2 min (seeding efficiency > 90%). The seeded scaffolds were cultured in spinner flasks for 2 days and then implanted into Lewis rats as aortic interposition grafts for 8 weeks. Results showed pericytes populated the porous layer of the scaffolds evenly and maintained their original phenotype after the dynamic culture. After implantation, pericyte-seeded TEVGs showed a significant higher patency rate than the unseeded control: 100% versus 38% (p < 0.05). Patent pericyte-seeded TEVGs revealed extensive tissue remodeling with collagen and elastin present. The remodeled tissue consisted of multiple layers of alpha-smooth muscle actin- and calponin-positive cells, and a von Willebrand factor-positive monolayer in the lumen. These results demonstrate the feasibility of a pericyte-based TEVG and suggest that the pericytes play a role in maintaining patency of the TEVG as an arterial conduit. PMID: 20684982 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | A review on endogenous regenerative technology in periodontal regenerative medicine. Biomaterials. 2010 Aug 2; Authors: Chen FM, Zhang J, Zhang M, An Y, Chen F, Wu ZF Periodontitis is a globally prevalent inflammatory disease that causes the destruction of the tooth-supporting apparatus and potentially leads to tooth loss. Currently, the methods to reconstitute lost periodontal structures (i.e. alveolar bone, periodontal ligament, and root cementum) have relied on conventional mechanical, anti-infective modalities followed by a range of regenerative procedures such as guided tissue regeneration, the use of bone replacement grafts and exogenous growth factors (GFs), and recently developed tissue engineering technologies. However, all current or emerging paradigms have either been shown to have limited and variable outcomes or have yet to be developed for clinical use. To accelerate clinical translation, there is an ongoing need to develop therapeutics based on endogenous regenerative technology (ERT), which can stimulate latent self-repair mechanisms in patients and harness the host's innate capacity for regeneration. ERT in periodontics applies the patient's own regenerative 'tools', i.e. patient-derived GFs and fibrin scaffolds, sometimes in association with commercialized products (e.g. Emdogain((R)) and Bio-Oss((R))), to create a material niche in an injured site where the progenitor/stem cells from neighboring tissues can be recruited for in situ periodontal regeneration. The choice of materials and the design of implantable devices influence therapeutic potential and the number and invasiveness of the associated clinical procedures. The interplay and optimization of each niche component involved in ERT are particularly important to comprehend how to make the desired cell response safe and effective for therapeutics. In this review, the emerging opportunities and challenges of ERT that avoid the ex vivo culture of autologous cells are addressed in the context of new approaches for engineering or regeneration of functional periodontal tissues by exploiting the use of platelet-rich products and its associated formulations as key endogenous resources for future clinical management of periodontal tissue defects. PMID: 20684986 [PubMed - as supplied by publisher] | | | | | | | | | | |  |
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