|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | Synthetic Adipose Tissue Models for Studying Mammary Gland Development and Breast Tissue Engineering. J Mammary Gland Biol Neoplasia. 2010 Sep 12; Authors: Wang X, Reagan MR, Kaplan DL The mammary gland is a dynamic organ that continually changes its architecture and function. Reciprocal interactions between epithelium and adipocyte-containing stroma exert profound effects on all stages of its development, even though the details of these events are not fully understood. To address this issue, enormous potential exists in the utilization of synthetic adipose tissue model systems to uncover the properties and functions of adipocytes in the mammary gland. The first part of this review focuses on mammary adipose tissue (or adipocyte)-related model systems developed in recent years and their utility in investigating adipose-epithelial interactions, mammary gland morphogenesis, development and tumorigenesis. The second part shifts to the field of adipose-based breast tissue engineering, focusing on how these synthetic adipose tissue models are being constructed in vitro or in vivo for regeneration of the mammary gland, and their potentials in adipose tissue engineering also are discussed. PMID: 20835885 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Sex differences in the benefits of rehabilitative training during adolescence following neonatal hypoxia-ischemia in rats. Exp Neurol. 2010 Sep 9; Authors: Tsuji M, Mishima K, Harada K, Fujiwara M, Ikeda T Much effort and many resources are being devoted to rehabilitative programs for children with disabilities caused by neonatal hypoxic-ischemic encephalopathy without clear evidence of the efficacy of such programs. We recently reported that rehabilitative training tasks during adolescence improve spatial learning impairment following neonatal hypoxic-ischemic injury in rats without histological improvement. In the present study we focused on sex differences. Wister rat pups were exposed to a unilateral hypoxic-ischemic insult at 7days of age. Six weeks after hypoxia-ischemia, rehabilitative training tasks were started. The tasks consisted of the plus maze, the eight-arm radial maze, and the choice reaction time task. Sixteen weeks after the insult, the water maze task was performed to evaluate spatial learning ability. Afterwards, we morphologically examined brain injury. Our rehabilitative training significantly improved swimming time and length in females (P<0.01) but not in males. Likewise, the training ameliorated infarct areas in the injured cerebral hemisphere in females but not in males (P < 0.01). These results suggest that it may be important to develop and evaluate cognitive rehabilitation programs for children with brain injury on the basis of gender. PMID: 20833167 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | An in situ formed biodegradable hydrogel for reconstruction of the corneal endothelium. Colloids Surf B Biointerfaces. 2010 Jul 30; Authors: Liang Y, Liu W, Han B, Yang C, Ma Q, Song F, Bi Q Biodegradable hydrogels are important biomaterials for tissue engineering and drug delivery. For the purpose of corneal regenerative medicine, we describe an in situ formed hydrogel based on a water-soluble derivative of chitosan, hydroxypropyl chitosan (HPCTS), and sodium alginate dialdehyde (SAD). Periodate oxidized alginate rapidly cross-links HPCTS due to Schiff's base formation between the available aldehyde and amino groups. Hydrogel cytotoxicity, degradability and histocompatibility in vivo were examined. The potential of the composite hydrogel for corneal endothelium reconstruction was demonstrated by encapsulating corneal endothelial cells (CECs) to grow on Descemet's membranes. The results demonstrate that the composite hydrogel was both non-toxic and biodegradable and that CECs transplanted by the composite hydrogel could survive and retain normal morphology. These results provide an opportunity for corneal endothelium reconstruction based on tissue engineering by the in situ formed composite hydrogel. PMID: 20832263 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Nanowastes and the environment: Potential new waste management paradigm. Environ Int. 2010 Sep 8; Authors: Musee N Recent exponential growth in the development of nanomaterials (NMs) and nanoproducts is premised on the provision of novel benefits to the society-through the exploitation of their unique industrial and biomedical applications like medical imaging, fabrics in textiles, tissue engineering, nanocomposites, bioremediation, and biomedicine. These NMs and nanoproducts have increased in quantity and volume from few kilograms to thousands of tonnes over the last fifteen to twenty years, and their uncontrolled release into the environment is anticipated to grow dramatically in future. However, their potential impacts to the biological systems are unknown. Among the key present challenges in the waste management sector include the emergence of nanowastes; however, the effectiveness and the capability of the current systems to handle them are yet to be established. Because of limited studies on nanowastes management, in this paper, three-fold objectives are pursued, namely; (i) to raise concerns related to the alarming increases of uncontrolled releases of NMs into the environment through nanowastes, (ii) examine the unique challenges nanowastes pose to the waste management systems-both from technological and legislative perspectives, and (iii) summarize results of the first nanowastes classification formalism in order to elucidate the potential challenges of waste streams containing nanoscale dimension materials to the present waste management paradigm. Finally, the article closes by summarizing several proactive steps of enhancing effective long-term and responsible management of nanowastes. PMID: 20832119 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Cell behavior on extracellular matrix mimic materials based on mussel adhesive protein fused with functional peptides. Biomaterials. 2010 Sep 8; Authors: Choi BH, Choi YS, Kang DG, Kim BJ, Song YH, Cha HJ Adhesion of cells to surfaces is a basic and important requirement in cell culture and tissue engineering. Here, we designed artificial extracellular matrix (ECM) mimics for efficient cellular attachment, based on mussel adhesive protein (MAP) fusion with biofunctional peptides originating from ECM materials, including fibronectin, laminin, and collagen. Cellular behaviors, including attachment, proliferation, spreading, viability, and differentiation, were investigated with the artificial ECM material-coated surfaces, using three mammalian cell lines (pre-osteoblast, chondrocyte, and pre-adipocyte). All cell lines examined displayed superior attachment, proliferation, spreading, and survival properties on the MAP-based ECM mimics, compared to other commercially available cell adhesion materials, such as poly-l-lysine and the naturally extracted MAP mixture. Additionally, the degree of differentiation of pre-osteoblast cells on MAP-based ECM mimics was increased. These results collectively demonstrate that the artificial ECM mimics developed in the present work are effective cell adhesion materials. Moreover, we expect that the MAP peptide fusion approach can be extended to other functional tissue-specific motifs. PMID: 20832110 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Rapid cellular internalization of multifunctional star polymers prepared by atom transfer radical polymerization. Biomacromolecules. 2010 Sep 13;11(9):2199-203 Authors: Cho HY, Gao H, Srinivasan A, Hong J, Bencherif SA, Siegwart DJ, Paik HJ, Hollinger JO, Matyjaszewski K Poly(ethylene glycol) (PEG) star polymers containing GRGDS (Gly-Arg-Gly-Asp-Ser) peptide sequences on the star periphery were synthesized by atom transfer radical polymerization (ATRP) of poly(ethylene glycol) methyl ether methacrylate (PEGMA), GRGDS modified poly(ethylene glycol) acrylate (GRGDS-PEG-Acryl), fluorescein o-methacrylate (FMA), and ethylene glycol dimethacrylate (EGDMA) via an "arm-first" method. Star polymers were approximately 20 nm in diameter, as measured by dynamic light scattering and atomic force microscopy. Conjugation of FMA to the stars was confirmed by fluorescence microscopy, and successful attachment of GRGDS segments to the star periphery was confirmed by (1)H NMR spectroscopy. Both fluorescent PEG star polymers with and without peripheral GRGDS peptide segments were cultured with MC3T3-E1.4 cells. These star polymers were biocompatible with ≥90% cell viability after 24 h of incubation. Cellular uptake of PEG star polymers in MC3T3-E1.4 cells was observed by confocal microscopy. Rapid uptake of PEG star polymers with GRGDS peptides (∼100% of FITC-positive cells in 15 min measured by flow cytometry) was observed, suggesting enhanced delivery potential of these functional star polymers. PMID: 20831270 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Surface-initiated assembly of protein nanofabrics. Nano Lett. 2010 Jun 9;10(6):2184-91 Authors: Feinberg AW, Parker KK Cells and tissues are self-organized within an extracellular matrix (ECM) composed of multifunctional, nano- to micrometer scale protein fibrils. We have developed a cell-free, surface-initiated assembly technique to rebuild this ECM structure in vitro. The matrix proteins fibronectin, laminin, fibrinogen, collagen type I, and collagen type IV are micropatterned onto thermosensitive surfaces as 1 to 10 nm thick, micrometer to centimeter wide networks, and released as flexible, free-standing nanofabrics. Independent control of microstructure and protein composition enables us to engineer the mechanical and chemical anisotropy. Fibronectin nanofabrics are highly extensible (>4-fold) and serve as scaffolds for engineering synchronously contracting, cardiac muscle; demonstrating biofunctionality comparable to cell-generated ECM. PMID: 20486679 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Effect of matrix composition on differentiation of nestin-positive neural progenitors from circulation into neurons. J Neural Eng. 2010 Jun;7(3):036009 Authors: Jose A, Krishnan LK The human peripheral blood mononuclear cell has a mixture of progenitor cells with potential to differentiate into a wide range of lineages. The ability of hematopoietic tissue-derived adult stem cells to differentiate into neural progenitor cells offers an alternative to embryonic stem cells as a viable source for cell transplantation therapies to cure neurodegenerative diseases. This approach could lead to the use of autologous progenitors from blood circulation; however, due to the limited numbers available, in vitro cell expansion may be indispensable. In addition, for successful transplantation there is the requirement of a delivery matrix on which cells can survive and differentiate. In this context we carried out this study to identify a suitable biodegradable matrix on which progenitor cells can home, multiply and differentiate. We designed different compositions of the biomimetic matrix containing fibrin, fibronectin, gelatin, growth factors, laminin and hyaluronic acid. The attached cells expressed proliferation markers in initial periods of culture and between days 6 and 9 in culture they differentiated into neurons and/or astrocytes. The differentiation of progenitors into neurons and asterocyte on the composed matrix was established by morphological and immunochemical analysis. Flow cytometric analysis of cells in culture was employed to track development of neurons which expressed an early marker beta-tubulin3 and a terminal marker microtubule-associated protein-2 at a later culture period. In vitro experiments indicate that a highly specific niche consisting of various components of the extracellular matrix, including hyaluronic acid, promote cell homing, survival and differentiation. PMID: 20479522 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Stimulation of functional vessel growth by gene therapy. Integr Biol (Camb). 2010 Mar;2(2-3):102-12 Authors: Korpisalo P, Ylä-Herttuala S The process of growing new blood vessels through gene therapy may be difficult but is certainly possible. This review will discuss the most important factors determining the efficacy of angiogenic gene therapy. PMID: 20473388 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Fusion of concentrically layered tubular tissue constructs increases burst strength. Ann Biomed Eng. 2010 Jun;38(6):2226-36 Authors: Huynh TN, Tranquillo RT Tubular tissue constructs prepared from neonatal human dermal fibroblasts entrapped in fibrin gel were incubated on a mandrel for three weeks to allow for initial fibrin remodeling into tissue before being concentrically layered and incubated for an additional three weeks on the mandrel. Upon harvest, double layer constructs were not statistically different from single layer control constructs in terms of length, collagen density, cell density, tensile modulus, or ultimate tensile strength. However, the thickness and burst pressure were both approximately twice the single layer control values. Metabolically active cells were detected at the interface, and scanning electron microscopy revealed fiber structures bridging the two layers, co-localizing with the cells, which exhibited minimal migration across the layers. In contrast, double layer constructs where tissue fusion was prohibited by mechanical distraction of the layers showed no increase in burst pressure despite having increased thickness and the same collagen and cell densities of the single layer control constructs; moreover, the burst failure occurred sequentially in the layers in contrast to simultaneous failure for the fused double layer constructs. This study provides insight into the nature of the interface and the role of cell behavior when tissue fusion occurs between two layers of bioartificial tissue in vitro. It also suggests a method for improving the burst strength of fibrin-based tubular tissue constructs by increasing the construct thickness via concentrically layering and fusing two constructs. PMID: 20431952 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Therapeutic cell delivery for in situ regenerative medicine. Adv Drug Deliv Rev. 2010 Jun 15;62(7-8):669-70 Authors: Wang DA, Mahato RI PMID: 20420868 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Bioactive stratified polymer ceramic-hydrogel scaffold for integrative osteochondral repair. Ann Biomed Eng. 2010 Jun;38(6):2183-96 Authors: Jiang J, Tang A, Ateshian GA, Guo XE, Hung CT, Lu HH Due to the intrinsically poor repair potential of articular cartilage, injuries to this soft tissue do not heal and require clinical intervention. Tissue engineered osteochondral grafts offer a promising alternative for cartilage repair. The functionality and integration potential of these grafts can be further improved by the regeneration of a stable calcified cartilage interface. This study focuses on the design and optimization of a stratified osteochondral graft with biomimetic multi-tissue regions, including a pre-designed and pre-integrated interface region. Specifically, the scaffold based on agarose hydrogel and composite microspheres of polylactide-co-glycolide (PLGA) and 45S5 bioactive glass (BG) was fabricated and optimized for chondrocyte density and microsphere composition. It was observed that the stratified scaffold supported the region-specific co-culture of chondrocytes and osteoblasts which can lead to the production of three distinct yet continuous regions of cartilage, calcified cartilage and bone-like matrices. Moreover, higher cell density enhanced chondrogenesis and improved graft mechanical property over time. The PLGA-BG phase promoted chondrocyte mineralization potential and is required for the formation of a calcified interface and bone regions on the osteochondral graft. These results demonstrate the potential of the stratified scaffold for integrative cartilage repair and future studies will focus on scaffold optimization and in vivo evaluations. PMID: 20411332 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Different properties of electrospun fibrous scaffolds of separated heavy-chain and light-chain fibroins of Bombyx mori. Int J Biol Macromol. 2010 Jun;46(5):493-501 Authors: Wadbua P, Promdonkoy B, Maensiri S, Siri S This study is the first to report on the fabrication and properties of electrospun scaffolds derived from separated light-chain fibroin and heavy-chain fibroin, two major proteins of silk fibroin. Among seven different extraction conditions, which were commonly used to extract fibroin from cocoons of Bombyx mori, only Ajisawa's reagent and 9 M lithium thiocyanate could extract both heavy-chain fibroin and light-chain fibroin, while the other conditions could yield only the light-chain fibroin. Mixed fibroin, light-chain fibroin, and heavy-chain fibroin were fabricated using electrospinning methods. Average diameters of the fibers were 658+/-208, 517+/-162, and 518+/-171 nm, respectively and their sizes after treatment with 50% methanol for 60 min were slightly increased to 747+/-244, 556+/-164 and 521+/-201 nm, respectively. FTIR spectra showed similar predominant beta-sheet conformation of mixed fibroin and heavy-chain fibroin scaffolds after treated with methanol, whereas the predominant structure of light-chain fibroin was random coil conformation. Although, scaffolds derived from mixed fibroin and heavy-chain fibroin showed similar properties, the light-chain fibroin scaffold clearly exhibited different properties, including more hydrophilic character, water uptake ability, degradation rate, and cell adhesion capability. PMID: 20338193 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Hydroxyapatite nanorods/poly(vinyl pyrolidone) composite nanofibers, arrays and three-dimensional fabrics: electrospun preparation and transformation to hydroxyapatite nanostructures. Acta Biomater. 2010 Aug;6(8):3013-20 Authors: Chen F, Tang QL, Zhu YJ, Wang KW, Zhang ML, Zhai WY, Chang J Electrospinning has been recognized as an efficient technique for fabricating polymer nanofibrous biomaterials. However, the study of electrospun inorganic biomaterials with well-designed three-dimensional (3-D) structures is still limited and little reported. In this study hydroxyapatite (HAp) nanorods with an average diameter of approximately 7 nm and length of approximately 27 nm were synthesized through a simple precipitation method and used for the fabrication of inorganic/organic [poly(vinyl pyrolidone) (PVP)] composite nanofibers by electrospinning in ethanol solution. 3-D fabrics and aligned nanofiber arrays of the HAp nanorods/PVP composite were obtained as precursors. Thereafter, 3-D single phase HAp fabrics, tubular structures and aligned nanofiber arrays were obtained after thermal treatment of the corresponding composite precursors. Cytotoxicity experiments indicated that the HAp fabric scaffold had good biocompatibility. In vitro experiments showed that mesenchymal stem cells could attach to the HAp fabric scaffold after culture for 24h. PMID: 20167294 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Varying the diameter of aligned electrospun fibers alters neurite outgrowth and Schwann cell migration. Acta Biomater. 2010 Aug;6(8):2970-8 Authors: Wang HB, Mullins ME, Cregg JM, McCarthy CW, Gilbert RJ Aligned, electrospun fibers have shown great promise in facilitating directed neurite outgrowth within cell and animal models. While electrospun fiber diameter does influence cellular behavior, it is not known how aligned, electrospun fiber scaffolds of differing diameter influence neurite outgrowth and Schwann cell (SC) migration. Thus, the goal of this study was to first create highly aligned, electrospun fiber scaffolds of varying diameter and then assess neurite and SC behavior from dorsal root ganglia (DRG) explants. Three groups of highly aligned, electrospun poly-l-lactic acid (PLLA) fibers were created (1325+383 nm, large diameter fibers; 759+179 nm, intermediate diameter fibers; and 293+65 nm, small diameter fibers). Embryonic stage nine (E9) chick DRG were cultured on fiber substrates for 5 days and then the explants were stained against neurofilament and S100. DAPI stain was used to assess SC migration. Neurite length and SC migration distance were determined. In general, the direction of neurite extension and SC migration were guided along the aligned fibers. On the small diameter fiber substrate, the neurite length was 42% and 36% shorter than those on the intermediate and large fiber substrates, respectively. Interestingly, SC migration did not correlate with that of neurite extension in all situations. SCs migrated equivalently with extending neurites in both the small and large diameter scaffolds, but lagged behind neurites on the intermediate diameter scaffolds. Thus, in some situations, topography alone is sufficient to guide neurites without the leading support of SCs. Scanning electron microscopy images show that neurites cover the fibers and do not reside exclusively between fibers. Further, at the interface between fibers and neurites, filopodial extensions grab and attach to nearby fibers as they extend down the fiber substrate. Overall, the results and observations suggest that fiber diameter is an important parameter to consider when constructing aligned, electrospun fibers for nerve regeneration applications. PMID: 20167292 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Microcapsules and microcarriers for in situ cell delivery. Adv Drug Deliv Rev. 2010 Jun 15;62(7-8):711-30 Authors: Hernández RM, Orive G, Murua A, Pedraz JL In recent years, the use of transplanted living cells pumping out active factors directly at the site has proven to be an emergent technology. However a recurring impediment to rapid development in the field is the immune rejection of transplanted allo- or xenogeneic cells. Immunosuppression is used clinically to prevent rejection of organ and cell transplants in humans, but prolonged usage can make the recipient vulnerable to infections, and increase the likelihood of tumorigenesis of the transplanted cells. Cell microencapsulation is a promising tool to overcome these drawbacks. It consists of surrounding cells with a semipermeable polymeric membrane. The latter permits the entry of nutrients and the exit of therapeutic protein products, obtaining in this way a sustained delivery of the desirable molecule. The membrane isolates the enclosed cells from the host immune system, preventing the recognition of the immobilization cells as foreign. This review paper intends to overview the current situation in the cell encapsulation field and discusses the main events that have occurred along the way. The technical advances together with the ever increasing knowledge and experience in the field will undoubtedly lead to the realization of the full potential of cell encapsulation in the future. PMID: 20153388 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Scaffold-free cell delivery for use in regenerative medicine. Adv Drug Deliv Rev. 2010 Jun 15;62(7-8):753-64 Authors: Kelm JM, Fussenegger M The development of cell-based therapies for diseased tissues is one of the most promising research directions in regenerative medicine. Cell-delivery methods are an essential part of cell therapy concepts. Therapies with the potential to become clinical routine will only be possible if these methods ensure efficient engraftment and therapeutically-relevant number of cells survive. Here we provide an overview of three different scaffold-free cell-delivery concepts: (i) single cell delivery, (ii) cell sheet engineering and (iii) microtissue technology. PMID: 20153387 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Therapeutic cell delivery and fate control in hydrogels and hydrogel hybrids. Adv Drug Deliv Rev. 2010 Jun 15;62(7-8):699-710 Authors: Wang C, Varshney RR, Wang DA Hydrogels are synthetic or natural polymer networks that closely mimic native extracellular matrices. As hydrogel-based vehicles are being increasingly employed in therapeutic cell delivery, two inherent traits of most common hydrogels, namely low cell affinity and high cell constraint, have significantly drawn the attention of biomedical community. These two properties lead to the unfavourable settlement of anchorage-dependent cells (ADCs) and unsatisfactory cell delivery or tissue formation in hydrogel matrices. Tissue engineers have correspondingly made many efforts involving chemical modification or physical hybridisation to facilitate ADC settlement and promote tissue formation. On the other hand, these two 'bio-inert' characteristics have particularly favoured oncological cell therapists, who expect to utilize hydrogels to provide sufficiently high confinement of the delivered cells for anti-cancer purposes. In general, control of cell fate and behaviours in these three-dimensional (3D) microenvironments has become the central aim for hydrogel-mediated cell delivery, towards which various models based on hydrogels and their hybrids have emerged. In this paper, we will first review the development of strategies aiming to overcome the aforementioned two 'shortcomings' by (i) establishing ADC survival and (ii) creating space for tissue formation respectively, and then introduce how people take advantage of these 'disadvantages' of hydrogel encapsulation for (iii) an enhanced confinement of cell motion. PMID: 20138940 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Porous tantalum structures for bone implants: fabrication, mechanical and in vitro biological properties. Acta Biomater. 2010 Aug;6(8):3349-59 Authors: Balla VK, Bodhak S, Bose S, Bandyopadhyay A The relatively high cost of manufacturing and the inability to produce modular implants have limited the acceptance of tantalum, in spite of its excellent in vitro and in vivo biocompatibility. In this article, we report how to process Ta to create net-shape porous structures with varying porosity using Laser Engineered Net Shaping (LENS) for the first time. Porous Ta samples with relative densities between 45% and 73% have been successfully fabricated and characterized for their mechanical properties. In vitro cell materials interactions, using a human fetal osteoblast cell line, have been assessed on these porous Ta structures and compared with porous Ti control samples. The results show that the Young's modulus of porous Ta can be tailored between 1.5 and 20 GPa by changing the pore volume fraction between 27% and 55%. In vitro biocompatibility in terms of MTT assay and immunochemistry study showed excellent cellular adherence, growth and differentiation with abundant extracellular matrix formation on porous Ta structures compared to porous Ti control. These results indicate that porous Ta structures can promote enhanced/early biological fixation. The enhanced in vitro cell-material interactions on the porous Ta surface are attributed to its chemistry, its high wettability and its greater surface energy relative to porous Ti. Our results show that these laser-processed porous Ta structures can find numerous applications, particularly among older patients, for metallic implants because of their excellent bioactivity. PMID: 20132912 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Electrospun fibrous scaffolds with multiscale and photopatterned porosity. Macromol Biosci. 2010 Mar 10;10(3):265-70 Authors: Sundararaghavan HG, Metter RB, Burdick JA The structural and mechanical properties of tissue engineered environments are crucial for successful cellular growth and tissue repair. Electrospinning is gaining wide attention for the fabrication of tissue engineered scaffolds, but the small pore sizes of these scaffolds limit cell infiltration and construct vascularization. To address this problem, we have combined electrospinning with photopatterning to create multiscale porous scaffolds. This process retains the fibrous nature of the scaffolds and permits enhanced cellular infiltration and vascularization when compared to unpatterned scaffolds. This is the first time that photopatterning has been utilized with electrospun scaffolds and is only now possible with the electrospinning of reactive macromers. PMID: 20014198 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Exploring atypical locations of mammalian neural stem cells: the human filum terminale. Arch Ital Biol. 2010 Jun;148(2):85-94 Authors: Varghese M, Olstorn H, Murrell W, Langmoen IA Neurogenesis is a multifactorial event determined by local environmental cues, inherent cellular program as well as cellular milieu and may not necessarily be restricted to the SVZ and SGZ. NSCs have been isolated from or neurogenesis has been demonstrated in traditionally non neurogenic regions. This more permissive view of neurogenesis, however, is not widely accepted due to concerns regarding the methodologies used. Furthermore, it is compounded by the fact that the basal levels of increased neurogenesis in such regions has not been completely confirmed and thus precludes a paradigm shift. Were this non limited view of neurogenesis to be generally accepted after thorough investigation, it would open new avenues for regenerative medicine and stem cell therapy. PMID: 20830971 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | A novel composition for the culture of human adipose stem cells which includes complement C3. Cytotechnology. 2010 Sep 11; Authors: Hareendran S, Sathishkumar S, Abbas S, Mackay AM, Rajan P Adipose tissue is an easily accessible and abundant source of stem cells. Adipose stem cells (ASCs) are currently being researched as treatment options for repair and regeneration of damaged tissues. The standard culture conditions used for expansion of ASCs contain fetal bovine serum (FBS) which is undefined, could transmit known and unknown adventitious agents, and may cause adverse immune reactions. We have described a novel culture condition which excludes the use of FBS and characterised the resulting culture. Human ASCs were cultured in the novel culture medium, which included complement protein C3. These cultures, called C-ASCs, were compared with ASCs cultured in medium supplemented with FBS. Analysis of ASCs for surface marker profile, proliferation characteristics and differentiation potential indicated that the C-ASCs were similar to ASCs cultured in medium containing FBS. Using a specific inhibitor, we show that C3 is required for the survival of C-ASCs. This novel composition lends itself to being developed into a defined condition for the routine culture of ASCs for basic and clinical applications. PMID: 20835846 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Cell-delivery therapeutics for adipose tissue regeneration. Adv Drug Deliv Rev. 2010 Jun 15;62(7-8):798-813 Authors: Bauer-Kreisel P, Goepferich A, Blunk T In reconstructive surgery, there is a tremendous clinical need for adequate implants to repair soft tissue defects resulting from traumatic injury, tumor resection, or congenital anomalies. Adipose tissue engineering holds the promise to provide answers to this still increasing demand. The current approaches to adipose tissue engineering are comprehensively reviewed detailing the different cell carriers under investigation. A special focus is put on the applied cells. The delivered mesenchymal stem cells act in a dual role as building block of the new tissue and modulators of the host response. The conditioning of the cells in vitro prior to implantation decisively influences the tissue development and long-term survival in vivo. The special role of vascularization in adipose engineering is discussed. In all parts, key messages are defined providing the base for future advances in the generation of fat substitutes. PMID: 20394786 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Nanogel engineering for new nanobiomaterials: from chaperoning engineering to biomedical applications. Chem Rec. 2010 Sep 10; Authors: Sasaki Y, Akiyoshi K Nanosize hydrogels (nanogels) are polymer nanoparticles with three-dimensional networks, formed by chemical and/or physical cross-linking of polymer chains. Recently, various nanogels have been designed, with a particular focus on biomedical applications. In this review, we describe recent progress in the synthesis of nanogels and nanogel-integrated hydrogels (nanogel cross-linked gels) for drug-delivery systems (DDS), regenerative medicine, and bioimaging. We also discuss chaperone-like functions of physical cross-linking nanogel (chaperoning engineering) and organic-inorganic hybrid nanogels. © 2010 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.201000008. PMID: 20836092 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Biophysics and dynamics of natural and engineered stem cell microenvironments. Wiley Interdiscip Rev Syst Biol Med. 2010 Jan;2(1):49-64 Authors: Keung AJ, Healy KE, Kumar S, Schaffer DV Stem cells are defined by their ability to self-renew and to differentiate into one or more mature lineages, and they reside within natural niches in many types of adult and embryonic tissues that present them with complex signals to regulate these two hallmark properties. The diverse nature of these in vivo microenvironments raises important questions about the microenvironmental cues regulating stem cell plasticity, and the stem cell field has built a strong foundation of knowledge on the biochemical identities and regulatory effects of the soluble, cellular, and extracellular matrix factors surrounding stem cells through the isolation and culture of stem cells in vitro within microenvironments that, in effect, emulate the properties of the natural niche. Recent work, however, has expanded the field's perspective to include biophysical and dynamic characteristics of the microenvironment. These include biomechanical characteristics such as elastic modulus, shear force, and cyclic strain; architectural properties such as geometry, topography, and dimensionality; and dynamic structures and ligand profiles. We will review how these microenvironmental characteristics have been shown to regulate stem cell fate and discuss future research directions that may help expand our current understanding of stem cell biology and aid its application to regenerative medicine. Copyright © 2009 John Wiley & Sons, Inc.For further resources related to this article, please visit the WIREs website. PMID: 20836010 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | High-mobility group box 1 (HMGB1) as a master regulator of innate immunity. Cell Tissue Res. 2010 Sep 11; Authors: Castiglioni A, Canti V, Rovere-Querini P, Manfredi AA Damage-associated molecular patterns (DAMPs) comprise intracellular molecules characterized by the ability to reach the extracellular environment, where they prompt inflammation and tissue repair. The high-mobility box group 1 (HMGB1) protein is a prototypic DAMP and is highly conserved in evolution. HMGB1 is released upon cell and tissue necrosis and is actively produced by immune cells. Evidence suggests that HMGB1 acts as a key molecule of innate immunity, downstream of persistent tissue injury, orchestrating inflammation, stem cell recruitment/activation, and eventual tissue remodeling. PMID: 20835834 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Sex differences in the benefits of rehabilitative training during adolescence following neonatal hypoxia-ischemia in rats. Exp Neurol. 2010 Sep 9; Authors: Tsuji M, Mishima K, Harada K, Fujiwara M, Ikeda T Much effort and many resources are being devoted to rehabilitative programs for children with disabilities caused by neonatal hypoxic-ischemic encephalopathy without clear evidence of the efficacy of such programs. We recently reported that rehabilitative training tasks during adolescence improve spatial learning impairment following neonatal hypoxic-ischemic injury in rats without histological improvement. In the present study we focused on sex differences. Wister rat pups were exposed to a unilateral hypoxic-ischemic insult at 7days of age. Six weeks after hypoxia-ischemia, rehabilitative training tasks were started. The tasks consisted of the plus maze, the eight-arm radial maze, and the choice reaction time task. Sixteen weeks after the insult, the water maze task was performed to evaluate spatial learning ability. Afterwards, we morphologically examined brain injury. Our rehabilitative training significantly improved swimming time and length in females (P<0.01) but not in males. Likewise, the training ameliorated infarct areas in the injured cerebral hemisphere in females but not in males (P < 0.01). These results suggest that it may be important to develop and evaluate cognitive rehabilitation programs for children with brain injury on the basis of gender. PMID: 20833167 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Streptozotocin-induced diabetic rat-derived bone marrow mesenchymal stem cells have impaired abilities in proliferation, paracrine, antiapoptosis, and myogenic differentiation. Transplant Proc. 2010 Sep;42(7):2745-52 Authors: Jin P, Zhang X, Wu Y, Li L, Yin Q, Zheng L, Zhang H, Sun C BACKGROUND: Diabetes has been widely recognized as a major risk factor for cardiovascular disease. With the development of the regenerative medicine, autologous bone marrow-derived mesenchymal stem cells (BMSCs), transplantation can effectively improve cardiac function after myocardial infarction. However, the BMSCs used in most previous studies are derived from young or normal donors. Little is know about the biological characters change of BMSCs in diabetes mellitus. METHODS: BMSCs were taken from the streptozotocin (STZ)-induced diabetic rats and normal control rats. Cell proliferation was evaluated by CCK-8 assay. Production of vascular endothelial growth factor (VEGF) and insulin-like growth factor (IGF)-1 were measured by enzyme-linked immunosorbent assay. Apoptosis under hypoxia and serum deprivation culture conditions were detected by Hoechst 33342 stain and flow cytometry. Myogenic differentiation, induced by 5-azacytidine was assessed by using immunocytochemical staining for the expression of sarcomeric α-actin and desmin. RESULTS: Diabetic rat models were successfully induced by intraperitoneal injection of STZ. The proliferative abilities of BMSCs derived from diabetic rats decreased significantly compared with that from normal rats (P < .05). Similar results were also presented in the cytokines (VEGF and IGF-1) release (P = .02 and P < .01, respectively) that the ability of antiapoptosis and myogenic differentiation decreased obviously between diabetes group and the normal control group (P < .01). CONCLUSION: BMSCs from STZ-induced diabetic rats could be successfully harvested and expanded in vitro culture condition; their morphology was very similar to normal control group, with minor changes. However, the proliferative and differentiation properties of diabetic BMSCs, as well as cytokine release and antiapoptosis ability, were significantly impaired. PMID: 20832580 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | An in situ formed biodegradable hydrogel for reconstruction of the corneal endothelium. Colloids Surf B Biointerfaces. 2010 Jul 30; Authors: Liang Y, Liu W, Han B, Yang C, Ma Q, Song F, Bi Q Biodegradable hydrogels are important biomaterials for tissue engineering and drug delivery. For the purpose of corneal regenerative medicine, we describe an in situ formed hydrogel based on a water-soluble derivative of chitosan, hydroxypropyl chitosan (HPCTS), and sodium alginate dialdehyde (SAD). Periodate oxidized alginate rapidly cross-links HPCTS due to Schiff's base formation between the available aldehyde and amino groups. Hydrogel cytotoxicity, degradability and histocompatibility in vivo were examined. The potential of the composite hydrogel for corneal endothelium reconstruction was demonstrated by encapsulating corneal endothelial cells (CECs) to grow on Descemet's membranes. The results demonstrate that the composite hydrogel was both non-toxic and biodegradable and that CECs transplanted by the composite hydrogel could survive and retain normal morphology. These results provide an opportunity for corneal endothelium reconstruction based on tissue engineering by the in situ formed composite hydrogel. PMID: 20832263 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Surface Modification of Polyimide Sheets for Regenerative Medicine Applications. Biomacromolecules. 2010 Sep 10; Authors: Van Vlierberghe S, Sirova M, Rossmann P, Thielecke H, Boterberg V, Rihova B, Schacht E, Dubruel P In the present work, two strategies were elaborated to surface-functionalize implantable polyimide sheets. In the first methodology, cross-linkable vinyl groups were introduced on the polyimide surface using aminopropylmethacrylamide. In the second approach, a reactive succinimidyl ester was introduced on the surface of PI. Using the former approach, the aim is to apply a vinyl functionalized biopolymer coating. In the latter approach, any amine containing biopolymer can be immobilized. The foils developed were characterized in depth using a variety of characterization techniques including atomic force microscopy, static contact angle measurements, and X-ray photoelectron spectroscopy. The results indicated that both modification strategies were successful. The subcutaneous implantation in mice indicated that both modification strategies resulted in biocompatible materials, inducing only limited cellular infiltration to the surrounding tissue. PMID: 20831199 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Exploring atypical locations of mammalian neural stem cells: the human filum terminale. Arch Ital Biol. 2010 Jun;148(2):85-94 Authors: Varghese M, Olstorn H, Murrell W, Langmoen IA Neurogenesis is a multifactorial event determined by local environmental cues, inherent cellular program as well as cellular milieu and may not necessarily be restricted to the SVZ and SGZ. NSCs have been isolated from or neurogenesis has been demonstrated in traditionally non neurogenic regions. This more permissive view of neurogenesis, however, is not widely accepted due to concerns regarding the methodologies used. Furthermore, it is compounded by the fact that the basal levels of increased neurogenesis in such regions has not been completely confirmed and thus precludes a paradigm shift. Were this non limited view of neurogenesis to be generally accepted after thorough investigation, it would open new avenues for regenerative medicine and stem cell therapy. PMID: 20830971 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Neurogenesis in the enteric nervous system. Arch Ital Biol. 2010 Jun;148(2):73-83 Authors: Metzger M The enteric nervous system (ENS) represents the highly organized intrinsic innervation of the gastrointestinal tract and plays a critical role for all stages of postnatal life. Severe disturbances of ENS function can significantly influence life quality or, in severe cases, can have acute life-threatening effects. Recent in vitro and in vivo studies demonstrated the persistence of neural stem cells in postnatal gut and there seem to be many interesting parallels to the more extensively studied neural stem cells in the brain. Enteric stem cells have been proposed as an appropriate cell source to provide an alternative therapeutic option for a number of neurogastrointestinal diseases, however a better understanding of these cells would be crucial for the translation of cell-based therapies into clinic. This review tries to highlight the recent findings in the field of enteric neurogenesis and additionally gives a brief overview about the development, structure and function of the ENS and about the developmental or age-related disturbances affecting the ENS. PMID: 20830970 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | A decade of mammalian retinal stem cell research. Arch Ital Biol. 2010 Jun;148(2):59-72 Authors: Locker M, El Yakoubi W, Mazurier N, Dullin JP, Perron M Ten years have now passed since the discovery of quiescent neural stem cells within the mammalian retina. Beside the fascinating aspect of stem cell biology in basic science, these cells have also offered hope for the treatment of incurable retinal diseases. The field has thus rapidly evolved, fluctuating between major advances and recurring doubts. In this review, we will retrace the efforts of scientists during this last decade to characterize these cells and to use them in regenerative medicine. We will also highlight advances made in animal models capable of stem cell-mediated retinal regeneration. PMID: 20830969 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Burgeoning stem cell product market lures major suppliers. Nat Biotechnol. 2010 Jun;28(6):535-6 Authors: Webb S PMID: 20531315 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Patterned transgene expression in multiple-channel bridges after spinal cord injury. Acta Biomater. 2010 Aug;6(8):2889-97 Authors: De Laporte L, Huang A, Ducommun MM, Zelivyanska ML, Aviles MO, Adler AF, Shea LD Patterning of gene delivery on sub-millimeter length scales within tissue engineering scaffolds is fundamental to recreating the complex architectures of tissues. Surface-mediated delivery of lipoplexes mixed with fibronectin was investigated to pattern vectors within 250 microm channels in poly(lactide-co-glycolide) (PLG) bridges. Initial studies performed in vitro on PLG surfaces indicated that a DNA density of 0.07 microg mm(-2) inside each channel with a weight ratio of DNA to fibronectin of 1:20 maximized the number of transfected cells and the levels of transgene expression. Patterned vectors encoding for nerve growth factor (NGF) resulted in localized neurite extension within the channel. Translation to three-dimensional multiple-channel bridges enabled patterned transfection of different vectors throughout the channels for DNA:fibronectin ratios of 1:4 and multiple DNA depositions, with a large increase of neural cell bodies and neurite extension for delivery of DNA encoding for NGF. In vivo, the immobilization of non-viral vectors within the channels resulted in localized transfection within the pore structure of the bridge immediately around the channels of the bridge containing DNA. This surface immobilization strategy enables patterned gene delivery in vitro and in vivo on length scales of hundreds of microns and may find utility in strategies aimed at regenerating tissues with complex architectures. PMID: 20167291 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Nanomaterials for in situ cell delivery and tissue regeneration. Adv Drug Deliv Rev. 2010 Jun 15;62(7-8):731-40 Authors: Wan AC, Ying JY Nanomaterials can be defined as materials that possess clearly defined features of less than 100nm, and whose nanostructured features confer characteristics crucial to the material's bulk property. The nanostructured features can be an intermediate or final state of the material in its synthesis process. The field of nanomaterials as applied to in situ cell delivery and tissue engineering is rapidly expanding. Nanomaterials that include peptide amphiphiles, self-assembling peptides, electrospun scaffolds, layer-by-layer complexes, nanotubes and nanocomposites have been applied to cell culture, encapsulation and delivery with promising results. As compared to scaffold-free cell delivery, nanomaterials are advantageous in terms of providing a means to control the biochemical and mechanical microenvironment of the cells. Nanomaterials are amenable to a bottom-up approach in functionalization and mechanical tuning, as illustrated in the examples presented in this review. Furthermore, nanomaterials such as DNA polyplexes and carbon nanotubes can also be incorporated into the cell delivery vehicle to improve the regenerative outcome. Lastly, while nanomaterials harbor much potential for cell delivery and tissue regeneration, further characterization is required in terms of clinical safety before these materials can be employed towards therapeutic applications. PMID: 20156499 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Microcapsules and microcarriers for in situ cell delivery. Adv Drug Deliv Rev. 2010 Jun 15;62(7-8):711-30 Authors: Hernández RM, Orive G, Murua A, Pedraz JL In recent years, the use of transplanted living cells pumping out active factors directly at the site has proven to be an emergent technology. However a recurring impediment to rapid development in the field is the immune rejection of transplanted allo- or xenogeneic cells. Immunosuppression is used clinically to prevent rejection of organ and cell transplants in humans, but prolonged usage can make the recipient vulnerable to infections, and increase the likelihood of tumorigenesis of the transplanted cells. Cell microencapsulation is a promising tool to overcome these drawbacks. It consists of surrounding cells with a semipermeable polymeric membrane. The latter permits the entry of nutrients and the exit of therapeutic protein products, obtaining in this way a sustained delivery of the desirable molecule. The membrane isolates the enclosed cells from the host immune system, preventing the recognition of the immobilization cells as foreign. This review paper intends to overview the current situation in the cell encapsulation field and discusses the main events that have occurred along the way. The technical advances together with the ever increasing knowledge and experience in the field will undoubtedly lead to the realization of the full potential of cell encapsulation in the future. PMID: 20153388 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Sol-gel silica-based biomaterials and bone tissue regeneration. Acta Biomater. 2010 Aug;6(8):2874-88 Authors: Arcos D, Vallet-Regà M The impact of bone diseases and trauma in developed and developing countries has increased significantly in the last decades. Bioactive glasses, especially silica-based materials, are called to play a fundamental role in this field due to their osteoconductive, osteoproductive and osteoinductive properties. In the last years, sol-gel processes and supramolecular chemistry of surfactants have been incorporated to the bioceramics field, allowing the porosity of bioglasses to be controlled at the nanometric scale. This advance has promoted a new generation of sol-gel bioactive glasses with applications such as drug delivery systems, as well as regenerative grafts with improved bioactive behaviour. Besides, the combination of silica-based glasses with organic components led to new organic-inorganic hybrid materials with improved mechanical properties. Finally, an effort has been made to organize at the macroscopic level the sol-gel glass preparation. This effort has resulted in new three-dimensional macroporous scaffolds, suitable to be used in tissue engineering techniques or as porous pieces to be implanted in situ. This review collects the most important advances in the field of silica glasses occurring in the last decade, which are called to play a lead role in the future of bone regenerative therapies. PMID: 20152946 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Bioengineering the skin-implant interface: the use of regenerative therapies in implanted devices. Ann Biomed Eng. 2010 Jun;38(6):2013-31 Authors: Peramo A, Marcelo CL This discussion and review article focuses on the possible use of regenerative techniques applied to the interfaces between skin and medical implants. As is widely known, the area of contact between an implant and the skin--the skin-implant interface--is prone to recurrent and persistent problems originated from the lack of integration between the material of the implant and the skin. Producing a long-term successful biointerface between skin and the implanted device is still an unsolved problem. These complications have prevented the development of advanced prosthetics and the evolution of biointegrated devices with new technologies. While previous techniques addressing these issues have relied mostly on the coating of the implants or the modification of the topology of the devices, recent in vitro developed techniques have shown that is possible to introduce biocompatible and possibly regenerative materials at the skin-device interface. These techniques have also shown that the process of delivering the materials has biological effects on the skin surrounding the implant, thus converting bioinert into bioactive, dynamic interfaces. Given that the best clinical outcome is the long-term stabilization and integration of the soft tissue around the implant, this article presents the basis for the selection of regenerative materials and therapies for long-term use at the skin-device interface, with focus on the use of natural biopolymers and skin cell transplantation. PMID: 20140520 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Therapeutic cell delivery and fate control in hydrogels and hydrogel hybrids. Adv Drug Deliv Rev. 2010 Jun 15;62(7-8):699-710 Authors: Wang C, Varshney RR, Wang DA Hydrogels are synthetic or natural polymer networks that closely mimic native extracellular matrices. As hydrogel-based vehicles are being increasingly employed in therapeutic cell delivery, two inherent traits of most common hydrogels, namely low cell affinity and high cell constraint, have significantly drawn the attention of biomedical community. These two properties lead to the unfavourable settlement of anchorage-dependent cells (ADCs) and unsatisfactory cell delivery or tissue formation in hydrogel matrices. Tissue engineers have correspondingly made many efforts involving chemical modification or physical hybridisation to facilitate ADC settlement and promote tissue formation. On the other hand, these two 'bio-inert' characteristics have particularly favoured oncological cell therapists, who expect to utilize hydrogels to provide sufficiently high confinement of the delivered cells for anti-cancer purposes. In general, control of cell fate and behaviours in these three-dimensional (3D) microenvironments has become the central aim for hydrogel-mediated cell delivery, towards which various models based on hydrogels and their hybrids have emerged. In this paper, we will first review the development of strategies aiming to overcome the aforementioned two 'shortcomings' by (i) establishing ADC survival and (ii) creating space for tissue formation respectively, and then introduce how people take advantage of these 'disadvantages' of hydrogel encapsulation for (iii) an enhanced confinement of cell motion. PMID: 20138940 [PubMed - indexed for MEDLINE] | | | | | | | | | |  | |  | |  |
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