| Platelet-rich plasma impairs osteoclast generation from human precursors of peripheral blood.
January 10, 2010 at 7:11 AM
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| | Platelet-rich plasma impairs osteoclast generation from human precursors of peripheral blood. J Orthop Res. 2010 Jan 7; Authors: Cenni E, Avnet S, Fotia C, Salerno M, Baldini N Platelet-rich plasma is used to accelerate bone repair for the release of osteogenic growth factors from activated platelets. To date, the effects on osteoclasts have been only scarcely investigated, even though these cells are crucial for bone remodeling. The aim of this research was the evaluation of the effects of thrombin-activated platelets (PRP) on osteoclastogenesis from human blood precursors. We evaluated both the ability to influence osteoclast differentiation induced by the receptor activator of nuclear factor-kappaB ligand (RANKL), and the ability to induce osteoclast differentiation without RANKL. In both assays, the incubation with PRP supernatant at 10% did not significantly affect the formation of tartrate-resistant acid phosphatase (TRACP)-positive multinucleated cells that were able to form the F-actin ring. However, when PRP at 25 and 50% was added to the medium without RANKL, the generation of TRACP-positive multinucleated cells was inhibited. ! PRP, even at 10%, reduced the osteoclast-mediated bone collagen degradation, suggesting inhibition of osteoclast activation. Similarly, after incubation with PRP supernatant, calcitonin receptor mRNA was lower than the untreated samples. In conclusion, PRP at 10% interfered with the complete differentiation process of human osteoclast precursors. At higher concentration it impaired osteoclast formation also at an early stage of differentiation. (c) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. PMID: 20058277 [PubMed - as supplied by publisher] | | |
| Bone marrow-derived mesenchymal stem cells express the pericyte marker 3G5 in culture and show enhanced chondrogenesis in hypoxic conditions.
January 10, 2010 at 7:11 AM
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| | Bone marrow-derived mesenchymal stem cells express the pericyte marker 3G5 in culture and show enhanced chondrogenesis in hypoxic conditions. J Orthop Res. 2010 Jan 7; Authors: Khan WS, Adesida AB, Tew SR, Lowe ET, Hardingham TE Bone marrow-derived mesenchymal stem cells are a potential source of cells for the repair of articular cartilage defects. Hypoxia has been shown to improve chondrogenesis in some cells. In this study, bone marrow-derived stem cells were characterized and the effects of hypoxia on chondrogenesis investigated. Adherent bone marrow colony-forming cells were characterized for stem cell surface epitopes, and then cultured as cell aggregates in chondrogenic medium under normoxic (20% oxygen) or hypoxic (5% oxygen) conditions. The cells stained strongly for markers of adult mesenchymal stem cells, and a high number of cells were also positive for the pericyte marker 3G5. The cells showed a chondrogenic response in cell aggregate cultures and, in lowered oxygen, there was increased matrix accumulation of proteoglycan, but less cell proliferation. In hypoxia, there was increased expression of key transcription factor SOX6, and of collagens II and XI, and aggrecan. Pericyte! s are a candidate stem cell in many tissue, and our results show that bone marrow-derived mesenchymal stem cells express the pericyte marker 3G5. The response to chondrogenic culture in these cells was enhanced by lowered oxygen tension. This has important implications for tissue engineering applications of bone marrow-derived stem cells. (c) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. PMID: 20058274 [PubMed - as supplied by publisher] | | |
| Chondrogenic differentiation and lubricin expression of caprine infraspinatus tendon cells.
January 10, 2010 at 7:11 AM
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| | Chondrogenic differentiation and lubricin expression of caprine infraspinatus tendon cells. J Orthop Res. 2010 Jan 7; Authors: Funakoshi T, Spector M Reparative strategies for the treatment of injuries to tendons, including those of the rotator cuff of the shoulder, need to address the formation of the cartilage which serves as the attachment apparatus to bone and which forms at regions undergoing compressive loading. Moreover, recent work indicates that cells employed for rotator cuff repair may need to synthesize a lubricating glycoprotein, lubricin, which has recently been found to play a role in tendon tribology. The objective of the present study was to investigate the chondrogenic differentiation and lubricin expression of caprine infraspinatus tendon cells in monolayer and three-dimensional culture, and to compare the behavior with bone marrow-derived mesenchymal stem cells (MSCs). The results demonstrated that while tendon cells in various media, including chondrogenic medium, expressed lubricin, virtually none of the MSCs synthesized this important lubricating molecule. Also of interest was that the ca! rtilage formation capacity of the tendon cells grown in pellet culture in chondrogenic medium was comparable with MSCs. These data inform the use of tendon cells for rotator cuff repair, including for fibrocartilaginous zones. (c) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. PMID: 20058273 [PubMed - as supplied by publisher] | | |
| Silk fibroin microparticles as carriers for delivery of human recombinant BMPs. Physical characterization and drug release.
January 10, 2010 at 7:11 AM
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| | Silk fibroin microparticles as carriers for delivery of human recombinant BMPs. Physical characterization and drug release. J Tissue Eng Regen Med. 2010 Jan 7; Authors: Bessa PC, Balmayor ER, Azevedo HS, Nürnberger S, Casal M, van Griensven M, Reis RL, Redl H Bone morphogenetic proteins (BMPs) are cytokines with strong ability to promote new bone formation. Herein, we report the use of silk fibroin microparticles as carriers for the delivery of BMP-2, BMP-9 or BMP-14. BMP-containing fibroin microparticles were prepared by a mild methodology using dropwise addition of ethanol, exhibiting mean diameters of 2.7 +/- 0.3 microm. Encapsulation efficiencies varied between 67.9 +/- 6.1 % and 97.7 +/- 2.0 % depending on the type and the amount of BMP loaded. Release kinetics showed that BMP-2, BMP-9 and BMP-14 were released in two phases profile, with a burst release in the first two days followed by a slower release, for a period of 14 days. The release data were best explained by Korsmeyer's model and the Fickian model of drug diffusion. Silk fibroin microparticles can offer a promising approach for the sustained delivery of different BMPs in tissue engineering applications. Copyright (c) 2010 John Wiley & Sons, Ltd. PMID: 20058243 [PubMed - as supplied by publisher] | | |
| Developments and challenges in human embryonic stem cell research in Spain.
January 10, 2010 at 7:11 AM
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| | Developments and challenges in human embryonic stem cell research in Spain. Stem Cell Rev. 2009 Dec;5(4):334-9 Authors: Cervera RP, Stojkovic M After years of following the trail of others, Spain is finally making a serious bid in science, specifically in regenerative medicine. In the framework of the European Union, Spain is setting up the basis for a solid collaborative network between public and private institutions, involving basic, translational, applied, technological and clinical researchers. In a society characterised by the idiom "slow but secure", it is still too soon to see the results of the huge economic and infrastructure investment made. We present here an overview of the challenges that have been surmounted and the ones that will have to be solved in order to situate Spain as a reference country in regenerative medicine worldwide. PMID: 20058198 [PubMed - in process] | | |
| Gene-Modified Stem Cells Combined with Rapid Prototyping Techniques: A Novel Strategy for Periodontal Regeneration.
January 10, 2010 at 7:11 AM
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| | Gene-Modified Stem Cells Combined with Rapid Prototyping Techniques: A Novel Strategy for Periodontal Regeneration. Stem Cell Rev. 2010 Jan 8; Authors: He H, Cao J, Wang D, Gu B, Guo H, Liu H Periodontal disease, a worldwide prevalent chronic disease in adults, is characterized by the destruction of the periodontal supporting tissue including the cementum, periodontal ligament and alveolar bone. The regeneration of damaged periodontal tissue is the main goal of periodontal treatment. Because conventional periodontal treatments remain insufficient to attain complete and reliable periodontal regeneration, periodontal tissue engineering has emerged as a prospective alternative method for improving the regenerative capacity of periodontal tissue. However, the potential of periodontal regeneration seems to be limited by the understanding of the cellular and molecular events in the formation of periodontal tissue and by the insufficient collaboration of multi-disciplinary research that periodontal tissue engineering involves. In this paper, we first reviewed the recent advancements in stem cells, signaling factors, and scaffolds that relate to periodontal re! generation. Then we speculate that specific genes would improve regenerative capacity of these stem cells, which could differentiate into cementoblasts, osteoblasts and fibroblasts. In addition, the 3D scaffolds that mimic the different structure and physiologic functions of natural fibro-osseous tissue could be fabricated by rapid prototyping (RP) techniques. It was therefore hypothesized that gene-modified stem cells combined with rapid prototyping techniques would be a new strategy to promote more effective and efficient periodontal regeneration. PMID: 20058102 [PubMed - as supplied by publisher] | | |
| Cellular interfacial and surface tensions determined from aggregate compression tests using a finite element model.
January 10, 2010 at 7:11 AM
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| | Cellular interfacial and surface tensions determined from aggregate compression tests using a finite element model. HFSP J. 2009 Aug;3(4):273-81 Authors: Brodland GW, Yang J, Sweny J Although previous studies suggested that the interfacial tension gamma(cc) acting along cell-cell boundaries and the effective viscosity mu of the cell cytoplasm could be measured by compressing a spherical aggregate of cells between parallel plates, the mechanical understanding necessary to extract this information from these tests-tests that have provided the surface tension sigma(cm) acting along cell-medium interfaces-has been lacking. These tensions can produce net forces at the subcellular level and give rise to cell motions and tissue reorganization, the rates of which are regulated by mu. Here, a three-dimensional (3D) cell-based finite element model provides insight into the mechanics of the compression test, where these same forces are at work, and leads to quantitative relationships from which the effective viscosity mu of the cell cytoplasm, the tension gamma(cc) that acts along internal cell-cell interfaces and the surface tension sigma(cp) along the ! cell-platen boundaries can be determined from force-time curves and aggregate profiles. Tests on 5-day embryonic chick mesencephalon, neural retina, liver, and heart aggregates show that all of these properties vary significantly with cell type, except gamma(cc), which is remarkably constant. These properties are crucial for understanding cell rearrangement and tissue self-organization in contexts that include embryogenesis, cancer metastases, and tissue engineering. PMID: 20057960 [PubMed - in process] | | |
| ECM-Based Materials in Cardiovascular Applications: Inherent Healing Potential and Augmentation of Native Regenerative Processes.
January 10, 2010 at 7:11 AM
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| | ECM-Based Materials in Cardiovascular Applications: Inherent Healing Potential and Augmentation of Native Regenerative Processes. Int J Mol Sci. 2009 Oct;10(10):4375-417 Authors: Piterina AV, Cloonan AJ, Meaney CL, Davis LM, Callanan A, Walsh MT, McGloughlin TM The in vivo healing process of vascular grafts involves the interaction of many contributing factors. The ability of vascular grafts to provide an environment which allows successful accomplishment of this process is extremely difficult. Poor endothelisation, inflammation, infection, occlusion, thrombosis, hyperplasia and pseudoaneurysms are common issues with synthetic grafts in vivo. Advanced materials composed of decellularised extracellular matrices (ECM) have been shown to promote the healing process via modulation of the host immune response, resistance to bacterial infections, allowing re-innervation and reestablishing homeostasis in the healing region. The physiological balance within the newly developed vascular tissue is maintained via the recreation of correct biorheology and mechanotransduction factors including host immune response, infection control, homing and the attraction of progenitor cells and infiltration by host tissue. Here, we review the pr! ogress in this tissue engineering approach, the enhancement potential of ECM materials and future prospects to reach the clinical environment. PMID: 20057951 [PubMed - in process] | | |
| Recent advances in synthetic bioelastomers.
January 10, 2010 at 7:11 AM
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| | Recent advances in synthetic bioelastomers. Int J Mol Sci. 2009 Oct;10(10):4223-56 Authors: Shi R, Chen D, Liu Q, Wu Y, Xu X, Zhang L, Tian W This article reviews the degradability of chemically synthesized bioelastomers, mainly designed for soft tissue repair. These bioelastomers involve biodegradable polyurethanes, polyphosphazenes, linear and crosslinked poly(ether/ester)s, poly(epsilon-caprolactone) copolymers, poly(1,3-trimethylene carbonate) and their copolymers, poly(polyol sebacate)s, poly(diol-citrates) and poly(ester amide)s. The in vitro and in vivo degradation mechanisms and impact factors influencing degradation behaviors are discussed. In addition, the molecular designs, synthesis methods, structure properties, mechanical properties, biocompatibility and potential applications of these bioelastomers were also presented. PMID: 20057942 [PubMed - in process] | | |
| Microwave-assisted synthesis of triple-helical, collagen-mimetic lipopeptides.
January 10, 2010 at 7:11 AM
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| | Microwave-assisted synthesis of triple-helical, collagen-mimetic lipopeptides. Nat Protoc. 2010;5(1):39-50 Authors: Banerjee J, Hanson AJ, Muhonen WW, Shabb JB, Mallik S Collagen-mimetic peptides and lipopeptides are widely used as substrates for matrix degrading enzymes, as new biomaterials for tissue engineering, as drug delivery systems and so on. However, the preparation and subsequent purification of these peptides and their fatty-acid conjugates are really challenging. Herein, we report a rapid microwave-assisted, solid-phase synthetic protocol to prepare the fatty-acid conjugated, triple-helical peptides containing the cleavage site for the enzyme matrix metalloproteinase-9 (MMP-9). We employed a PEG-based resin as the solid support and the amino acids were protected with Fmoc- and tert-butyl groups. The amino acids were coupled at 50 degrees C (25 W of microwave power) for 5 min. The deprotection reactions were carried out at 75 degrees C (35 W of microwave power) for 3 min. Using this protocol, a peptide containing 23 amino acids was synthesized and then conjugated to stearic acid in 14 h. PMID: 20057380 [PubMed - in process] | | |
| A novel calcium phosphate ceramic-magnetic nanoparticle composite as a potential bone substitute.
January 10, 2010 at 7:11 AM
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| | A novel calcium phosphate ceramic-magnetic nanoparticle composite as a potential bone substitute. Biomed Mater. 2010 Jan 7;5(1):15001 Authors: Wu Y, Jiang W, Wen X, He B, Zeng X, Wang G, Gu Z A magnetic field has been applied to accelerate bone healing for a long time. In this study, in order to combine the bone repair capability of calcium phosphate (CaP) ceramics with the magnetic field, a novel CaP ceramic-magnetic nanoparticle (CaP-MNP) composite was fabricated through integrating the superparamagnetic nanoparticles into the CaP ceramics. Two kinds of CaP ceramics were chosen: hydroxyapatite (HA) and HA/tricalcium phosphate (65/35, HT). The samples were cultured with Ros17/2.8 and MG63 cells respectively in vitro to evaluate the cell proliferation and differentiation via MTT and alkaline phosphatase activity tests. In order to find the influence of the magnetic materials on the expression of the bone morphological protein (BMP), the samples composited with BMP-2 were implanted subcutaneously in the fasciae of rat back muscles for 30 days. Compared with ordinary CaP ceramics, the results indicated that the CaP-MNP composite had good biocompatibility! and was able to promote cell proliferation and differentiation significantly. The in vivo test showed that the expression of BMP-2 would be accelerated by HT composited with MNPs, and new bone-like tissue formation could be observed. Accordingly, it might be expected that this CaP-MNP composite could become a potential bone substitute or bone tissue engineering scaffold. PMID: 20057017 [PubMed - as supplied by publisher] | | |
| Phase transformation behaviour of hydroxyapatite foams subject to heat treatment.
January 10, 2010 at 7:11 AM
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| | Phase transformation behaviour of hydroxyapatite foams subject to heat treatment. Biomed Mater. 2010 Jan 7;5(1):15004 Authors: Finoli A, McKeel D, Gerlach J, Nettleship I This study examined the relationship between sintering and phase transformation behaviour in hydroxyapatite (HA). Pellets and replicated foams were sintered at five different temperatures ranging from 1350 degrees C to 1550 degrees C. Hydroxyapatite remained as the major phase in all the samples studied. In the pellets, sintering took place prior to the phase transformation which occurs primarily at the surface. This created damage that extended into the interior of the pellet above 1400 degrees C. In contrast, the foams transformed at lower temperatures due to the higher surface area. This did not create damage in the foam. The differences in the foams and the pellets are discussed in terms of sintering and phase transformation behaviour. PMID: 20057016 [PubMed - as supplied by publisher] | | |
| Conversion of borate-based glass scaffold to hydroxyapatite in a dilute phosphate solution.
January 10, 2010 at 7:11 AM
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| | Conversion of borate-based glass scaffold to hydroxyapatite in a dilute phosphate solution. Biomed Mater. 2010 Jan 7;5(1):15005 Authors: Liu X, Pan H, Fu H, Fu Q, Rahaman MN, Huang W Porous scaffolds of a borate-based glass (composition in mol%: 6Na(2)O, 8K(2)O, 8MgO, 22CaO, 36B(2)O(3), 18SiO(2), 2P(2)O(5)), with interconnected porosity of approximately 70% and pores of size 200-500 microm, were prepared by a polymer foam replication technique. The degradation of the scaffolds and conversion to a hydroxyapatite-type material in a 0.02 M K(2)HPO(4) solution (starting pH = 7.0) at 37 degrees C were studied by measuring the weight loss of the scaffolds, as well as the pH and the boron concentration of the solution. X-ray diffraction, scanning electronic microscopy and energy dispersive x-ray analysis showed that a hydroxyapatite-type material was formed on the glass surface within 7 days of immersion in the phosphate solution. Cellular response to the scaffolds was assessed using murine MLO-A5 cells, an osteogenic cell line. Scanning electron microscopy showed that the scaffolds supported cell attachment and proliferation during the 6 day incubat! ion. The results indicate that this borate-based glass could provide a promising degradable scaffold material for bone tissue engineering applications. PMID: 20057014 [PubMed - as supplied by publisher] | | |
| Preparation of nanofibers containing the microalga Spirulina (Arthrospira).
January 10, 2010 at 7:11 AM
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| | Preparation of nanofibers containing the microalga Spirulina (Arthrospira). Bioresour Technol. 2009 Dec 26; Authors: de Morais MG, Stillings C, Dersch R, Rudisile M, Pranke P, Costa JA, Wendorff J Spirulina is a microalga which offers biological functions highly favorable for tissue engineering. Highly porous scaffolds can be produced by electrospinning containing biomass of Spirulina. The goal of this contribution was therefore to establish spinning conditions allowing to produce well defined nanofibers with diameters down to about 100nm and to produce nanofibers with various concentration of the biomass for subsequent studies in tissue engineering applications. The experimental results reveal that the blend system PEO/biomass is behaved surprisingly well in electrospinning. Very thin bead-free nanofibers with diameters of about 110nm can be produced for different biomass contents of up to 67wt.% of the nanofibers and for PEO concentrations in the spinning solution well below 4wt.%. These results suggest to us the use of the biomass containing nanofibers as extracellular matrices for stem cell culture and future treatment of spinal chord injury. PMID: 20056537 [PubMed - as supplied by publisher] | | |
| Can tissue engineering concepts advance tumor biology research?
January 10, 2010 at 7:11 AM
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| | Can tissue engineering concepts advance tumor biology research? Trends Biotechnol. 2010 Jan 5; Authors: Hutmacher DW, Loessner D, Rizzi S, Kaplan DL, Mooney DJ, Clements JA Advances in tissue engineering have traditionally led to the design of scaffold- or matrix-based culture systems that better reflect the biological, physical and biochemical environment of the natural extracellular matrix. Although their clinical applications in regenerative medicine tend to receive most of the attention, it is obvious that other areas of biomedical research could be well served by the powerful tools that have already been developed in tissue engineering. In this article, we review the recent literature to demonstrate how tissue engineering platforms can enhance in vitro and in vivo models of tumorigenesis and thus hold great promise to contribute to future cancer research. PMID: 20056286 [PubMed - as supplied by publisher] | | |
| A Streptococcus pyogenes derived collagen-like protein as a non-cytotoxic and non-immunogenic cross-linkable biomaterial.
January 10, 2010 at 7:11 AM
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| | A Streptococcus pyogenes derived collagen-like protein as a non-cytotoxic and non-immunogenic cross-linkable biomaterial. Biomaterials. 2010 Jan 5; Authors: Peng YY, Yoshizumi A, Danon SJ, Glattauer V, Prokopenko O, Mirochnitchenko O, Yu Z, Inouye M, Werkmeister JA, Brodsky B, Ramshaw JA A range of bacteria have been shown to contain collagen-like sequences that form triple-helical structures. Some of these proteins have been shown to form triple-helical motifs that are stable around body temperature without the inclusion of hydroxyproline or other secondary modifications to the protein sequence. This makes these collagen-like proteins particularly suitable for recombinant production as only a single gene product and no additional enzyme needs to be expressed. In the present study, we have examined the cytotoxicity and immunogenicity of the collagen-like domain from Streptococcus pyogenes Scl2 protein. These data show that the purified, recombinant collagen-like protein is not cytotoxic to fibroblasts and does not elicit an immune response in SJL/J and Arc mice. The freeze dried protein can be stabilised by glutaraldehyde cross-linking giving a material that is stable at >37 degrees C and which supports cell attachment while not causing loss of! viability. These data suggest that bacterial collagen-like proteins, which can be modified to include specific functional domains, could be a useful material for medical applications and as a scaffold for tissue engineering. PMID: 20056274 [PubMed - as supplied by publisher] | | |
| Physical surface and electromechanical properties of doped polypyrrole biomaterials.
January 10, 2010 at 7:11 AM
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| | Physical surface and electromechanical properties of doped polypyrrole biomaterials. Biomaterials. 2010 Jan 5; Authors: Gelmi A, Higgins MJ, Wallace GG Conducting polymers doped with biomolecules (biodopants) are becoming more widely evaluated for use as biomaterials. The use of biodopants is intended to enhance the compatibility of the polymers, however their effect on the physical properties of the final composite material has generally been less of a consideration. Here, we have characterised the physical surface properties of polypyrrole substrates doped with extracellular matrix and non-biological molecules using Atomic Force Microscopy (AFM) and Electrochemical AFM (EC-AFM) techniques. The physical parameters of the differently doped films ranged between 5 and 32nm for the RMS roughness, 30-1000MPa for the Young's modulus, and 1.6-4.7% for the actuation strain. It was found that irrespective of whether the dopant was biologically derived, the physical properties tended to group together with films having either a low roughness, low modulus and high strain, or vice versa. When compared to our previous study,! which investigated these polymers as potential biomaterials for supporting the growth and differentiation of skeletal muscle cells, these two groupings of the parameters correlated with the differing ability of the polypyrrole substrates to support the cells. Thus, in addition to the chemical advantage gained from using biodopants, the resulting physical properties of the polymer material should also be considered in their design as biomaterials for tissue engineering applications. PMID: 20056273 [PubMed - as supplied by publisher] | | |
| Strategies for cell manipulation and skeletal tissue engineering using high-throughput polymer blend formulation and microarray techniques.
January 10, 2010 at 7:11 AM
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| | Strategies for cell manipulation and skeletal tissue engineering using high-throughput polymer blend formulation and microarray techniques. Biomaterials. 2010 Jan 5; Authors: Khan F, Tare RS, Kanczler JM, Oreffo RO, Bradley M A combination of high-throughput material formulation and microarray techniques were synergistically applied for the efficient analysis of the biological functionality of 135 binary polymer blends. This allowed the identification of cell-compatible biopolymers permissive for human skeletal stem cell growth in both in vitro and in vivo applications. The blended polymeric materials were developed from commercially available, inexpensive and well characterised biodegradable polymers, which on their own lacked both the structural requirements of a scaffold material and, critically, the ability to facilitate cell growth. Blends identified here proved excellent templates for cell attachment, and in addition, a number of blends displayed remarkable bone-like architecture and facilitated bone regeneration by providing 3D biomimetic scaffolds for skeletal cell growth and osteogenic differentiation. This study demonstrates a unique strategy to generate and identify innovati! ve materials with widespread application in cell biology as well as offering a new reparative platform strategy applicable to skeletal tissues. PMID: 20056271 [PubMed - as supplied by publisher] | | |
| Metalloproteinase Expression is Associated with Traumatic Wound Failure.
January 10, 2010 at 7:11 AM
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| | Metalloproteinase Expression is Associated with Traumatic Wound Failure. J Surg Res. 2009 Sep 15; Authors: Utz ER, Elster EA, Tadaki DK, Gage F, Perdue PW, Forsberg JA, Stojadinovic A, Hawksworth JS, Brown TS BACKGROUND: Matrix metalloproteinases (MMPs) are crucial in the inflammatory and remodeling phases of wound healing. We previously reported the correlation between pro-inflammatory cytokines and timing of successful combat-wound closure. We now extend our studies to investigate the correlation between wound-remodeling MMP expression and wound healing. METHODS: Thirty-eight wounds in 25 patients with traumatic extremity combat wounds were prospectively studied. Surgical debridement with vacuum-assisted closure (VAC) device application was repeated every 48 to 72h until surgical wound closure. Wound effluent and patient serum were collected at each wound debridement and analyzed for five matrix metalloproteinases using the Luminex multiplex system; Millipore Corp, Billerica, MA. The primary outcome was wound healing within 30 d of definitive wound closure. Impairment was defined as delayed wound closure (>21 d from injury) or wound dehiscence. MMP expression was ! compared between impaired and normal healing wounds. RESULTS: Elevated levels of serum MMP-2 and MMP-7 and reduced levels of effluent MMP3 were seen in impaired wounds (n = 9) compared with wounds that healed (n = 29; P<0.001). Receiver operating characteristic (ROC) curve analysis yielded area-under-the-curve (AUC) of 0.744, 0.783, and 0.805, respectively. CONCLUSIONS: Impaired wound healing is characterized by pro-inflammatory MMP-2 and MMP-7. Serum and effluent concentrations of MMP-2, MMP-3, and MMP-7 can effectively predict the outcome of traumatic war wounds and can potentially provide decision-supportive, objective evidence for the timing of wound closure. PMID: 20056248 [PubMed - as supplied by publisher] | | |
| Multi-functional P(3HB) microsphere/45S5 Bioglass((R))-based composite scaffolds for bone tissue engineering.
January 10, 2010 at 7:11 AM
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| | Multi-functional P(3HB) microsphere/45S5 Bioglass((R))-based composite scaffolds for bone tissue engineering. Acta Biomater. 2010 Jan 4; Authors: Francis L, Meng D, Knowles JC, Roy I, Boccaccini AR Novel multi-functional P(3HB) microsphere/45S5 Bioglass((R))-based composite scaffolds exhibiting potential for drug delivery were developed for bone tissue engineering. 45S5 Bioglass((R))-based glass-ceramic scaffolds of high interconnected porosity produced using the foam-replication technique were coated with biodegradable microspheres (size < 2 mum) made from poly(3-hydroxybutyrate), P(3HB), produced using Bacillus cereus SPV. A solid-oil-in-water emulsion solvent extraction /evaporation technique was used to produce these P(3HB) microspheres. A simple slurry-dipping method, using a 1 wt % suspension of P(3HB) microspheres in water, dispersed by an ultrasonic bath, was used to coat the scaffold, producing a uniform microsphere-coating throughout the 3D scaffold structure. Compressive strength tests confirmed that the microsphere-coating slightly enhanced the scaffold mechanical strength. It was also confirmed that the microsphere-coating did not inhibit the! bioactivity of the scaffold when immersed in simulated body fluid (SBF) for up to 4 weeks. The hydroxyapatite (HA) growth rate on P(3HB) microsphere coated 45S5 Bioglass((R)) composite scaffolds was very similar to that on the uncoated control sample, qualitatively indicating similar bioactivity. However, the surface topography of the HA surface layer was affected as shown by results obtained from white light interferometry. The roughness of the surface was much higher for the P(3HB) microsphere-coated scaffolds than for the uncoated samples, after seven days in SBF. This feature would facilitate cell attachment and proliferation. Finally, gentamycin was successfully encapsulated into the P(3HB) microspheres to demonstrate the drug delivery capability of the scaffolds. Gentamycin release kinetics was determined using liquid chromatography-mass spectrometry (LC-MS). The release of the drug from the coated composite scaffolds was slow and controlled when compared to the obse! rved fast and relatively uncontrolled drug release from the bo! ne scaff old (without microsphere coating). Thus, this unique multifunctional bioactive composite scaffold has the potential to enhance cell attachment and to provide controlled delivery of relevant drugs for bone tissue engineering. PMID: 20056174 [PubMed - as supplied by publisher] | | |
| Emerging drugs for acute myocardial infarction.
January 10, 2010 at 7:11 AM
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| | Emerging drugs for acute myocardial infarction. Expert Opin Emerg Drugs. 2010 Jan 7; Authors: Lazzeri C, Tarquini R, Valente S, Abbate R, Gensini G Importance of the field: The present review is aimed at going over the pharmacological profile (and the clinical impact) of the emerging drugs involved in the management of patients with ST-elevation myocardial infarction (STEMI) in order to provide the cardiologists who deal with these patients in the early phase with the most recent evidence on this topic.Areas covered in this review: Anticoagulant and antiplatelet drugs are the main cornerstones of therapy in the treatment of STEMI patients undergoing primary percutaneous coronary intervention (PCI). The main issues that clinicians have to deal with are represented by balancing thrombotic and bleeding risks. In tailoring therapy, variables such as age, sex and previous disease should be taken into account, as well as ongoing complications (such as acute renal failure) that could affect hemostasis. Despite the well-established clinical benefits of antiplatelet agents, questions remain, mainly surrounding potenti! al for variable platelet response, which are strictly related to non-genetic (i.e., diet, drug-drug interaction, clinical factors such as obesity, diabetes mellitus, and inflammation) and genetic determinants. What the reader will gain: In their daily practice, cardiologists cannot abstract from the knowledge and updating on the ongoing research fields as well as the newly developed drugs, which they should frame in the very patient in the attempt to the develop a personalized medical strategy. These include also the pharmacological option(s) in the treatment of the reperfusion injury, the metabolic aspects and the stem cell therapy. Take home massage: In our opinion, the goal of ongoing research on the pharmacological approach to STEMI patients is a personalized medical strategy that relies on critical clinicians who merge newly developed acquisitions on this topic and a more complete, systemic and critical approach to the patient. PMID: 20055689 [PubMed - as supplied by publisher] | | |
| Cultivating regenerative medicine innovation in China.
January 10, 2010 at 7:11 AM
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| | Cultivating regenerative medicine innovation in China. Regen Med. 2010 Jan;5(1):35-44 Authors: McMahon DS, Thorsteinsdóttir H, Singer PA, Daar AS AIM: While China has become a significant contributor and prolific publisher in regenerative medicine, its role in the field is not well understood. We analyze how capacity in regenerative medicine was built in China to identify some of its main strengths and challenges. MATERIALS & METHODS: This case study of regenerative medicine in China is primarily based on interviews with experts in China, including researchers, policy makers, clinicians, representatives of firms and regulators. RESULTS: Our analysis shows that diverse groups are active in this field in China. Leading research groups are contributing extensively to international peer-reviewed journals. Strong governmental support and recruitment of highly trained Chinese scientists from abroad has made it possible for China to rapidly build up capacity in regenerative medicine. However, some hospitals in China are offering stem cell therapies with limited scientific evidence supporting their efficacy/saf! ety, and international skepticism of medical research in China presents a challenge to the development of the field. CONCLUSION: China has been able to catapult itself into the forefront of regenerative medicine but needs to address current regulatory challenges in order to secure its position in this emerging field. PMID: 20055687 [PubMed - in process] | | |
| 3D PLGA scaffolds improve differentiation and function of bone marrow mesenchymal stem cell-derived hepatocytes.
January 10, 2010 at 7:11 AM
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| | 3D PLGA scaffolds improve differentiation and function of bone marrow mesenchymal stem cell-derived hepatocytes. Stem Cells Dev. 2010 Jan 7; Authors: Li J, Tao R, Wu W, Cao H, Xin J, Li J, Guo J, Jiang L, Gao C, Demetriou AA, Farkas DL, Li L Liver tissue engineering with hepatic stem cells provides a promising alternative to liver transplantation in patients with acute and chronic hepatic failure. In this study, a three-dimensional (3D) bioscaffold was introduced for differentiation of rat bone marrow mesenchymal stem cells (BMSCs) into hepatocytes. For hepatocyte differentiation, third passage BMSCs isolated from normal adult F344 rats were seeded into collagen coated poly (lactic-co-glycolic acid) (C-PLGA) 3D scaffolds with hepatocyte differentiation medium for 3 weeks. Hepatogenesis in scaffold was characterized by reverse transcript PCR, Western Blot, confocal laser scanning microscopy, Periodic Acid-Schiff staining, histochemistry and biochemical assays with hepatic-specific genes and markers. A monolayer culture system was used as a control differentiation group. The results showed that isolated cells possessed the basic features of BMSCs. Differentiated hepatocyte-like cells in C-PLGA scaffolds! expressed hepatocyte-specific markers (e.g. albumin, alpha fetoprotein, cytokeratin-18, hepatocyte nuclear factor-4alpha and cytochrome P450) at mRNA and protein level. Most markers were expressed in C-PLGA group one week earlier than in the control group. Results of biocompatibility indicated that the differentiated hepatocyte-like cells grew more stably in C-PLGA scaffolds than that in controls during a three-week differentiation period. The significantly higher metabolic functions in hepatocyte-like cells in C-PLGA scaffold group further demonstrated the important role of the scaffold. Conclusion: As the phenomenon of transdifferentiation is uncommon, our successful transdifferentiation rates of BMSCs to mature hepatocytes prove the superiority of the C-PLGA scaffold in providing a suitable environment for such a differentiation. This material can possibly be used as a bioscaffold for liver tissue engineering in future clinical therapeutic applications. PMID: 20055663 [PubMed - as supplied by publisher] | | |
| Dental Stem Cell therapy with Calcium Hydroxide in Dental Pulp Capping.
January 10, 2010 at 7:11 AM
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| | Dental Stem Cell therapy with Calcium Hydroxide in Dental Pulp Capping. Tissue Eng Part A. 2010 Jan 7; Authors: Ji YM, Jeon SH, Park JY, Chung JH, Choung YH, Choung PH Calcium hydroxide has been extensively and steadily used for direct pulp capping in modern clinical dentistry. As it was known to have potential to induce hard tissue repair, this chemical has been applied to the exposed dental pulp and the hard tissue is expected to be regenerated above the pulp. During the reparative process of exposed pulp, primary odontoblasts lost as a result of extensive damage are replaced with newly differentiated odontoblast-like cells. This process is known to follow the sequential steps of proliferation, migration, and differentiation of progenitor cells. This research will examine the relationship between calcium hydroxide and the recruitment, proliferation and mineralization of postnatal dental stem cells, obtained from an immature dental tissue of beagle dogs. Immunocytochemical staining and RT-PCR were used to identify the putative stem cell markers. Immunoblot analysis, wound healing assay, cell migration assay and Alizarin red sta! ining were used to evaluate proliferation, migration and mineralization capacity of the calcium hydroxide-treated stem cells. As an in vivo study, combination of calcium hydroxide and autogenous dental pulp stem cells was applied for the treatment of intentionally created tooth defects on the premolars and the molars in beagle dogs to observe dentin regeneration. Ex-vivo expanded dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs) expressed STRO-1 and CD146, the mesenchymal stem cell markers. It was evident that calcium hydroxide increased recruitment, migration, proliferation and mineralization of the DPSCs and PDLSCs. Such results are valuable for the future availability of the DPSCs, which are recently focused as the stem cell reservoir for regeneration of dentin upon tooth injury, as well as for elucidation of the role of calcium hydroxide in pulp capping therapy. PMID: 20055661 [PubMed - as supplied by publisher] | | |
| Biodegradable polyphosphazene-nanohydroxyapatite composite nanofibers: scaffolds for bone tissue engineering.
January 10, 2010 at 7:11 AM
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| | Biodegradable polyphosphazene-nanohydroxyapatite composite nanofibers: scaffolds for bone tissue engineering. J Biomed Nanotechnol. 2009 Feb;5(1):69-75 Authors: Bhattacharyya S, Kumbar SG, Khan YM, Nair LS, Singh A, Krogman NR, Brown PW, Allcock HR, Laurencin CT Bone is a natural composite comprised of hierarchically arranged collagen fibrils, hydroxyapatite and proteoglycans in the nanometer scale. This preliminary study reports the fabrication of biodegradable poly[bis(ethyl alanato)phosphazene]-nanohydroxyapatite (PNEA-nHAp) composite nanofiber matrices via electrospinning. Binary solvent compositions of THF and ethanol were used as a spinning solvent to attain better nanohydroxyapatite dispersibility in PNEA solution. These nanocomposites were characterized for morphology, nHAp distribution and content using spectroscopy and gravimetric estimations. Composite nanofibers fabricated in the diameter range of 100-310 nm could encapsulate 20-40 nm nHAp crystals. A better composite nanofiber yield was obtained for 50% (w/w) nHAp experimental loadings. Incremental experimental loading beyond 60% (w/w) hindered electrospinning due to polymer-nHAp phase separation. Composites nanofibers had a rougher surface and nodules along ! the length of the fibers suggesting nHAp encapsulation. Further, characterization via energy dispersive X-ray spectroscopy and X-ray mapping confirmed the nHAp encapsulation. Providing cells with a natural bone like environment with a fibrillar structure and natural hydroxyapatite can enhance bone tissue regeneration/repair. PMID: 20055108 [PubMed - in process] | | |
| Electrospinning: methods and development of biodegradable nanofibres for drug release.
January 10, 2010 at 7:11 AM
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| | Electrospinning: methods and development of biodegradable nanofibres for drug release. J Biomed Nanotechnol. 2009 Feb;5(1):1-19 Authors: Ashammakhi N, Wimpenny I, Nikkola L, Yang Y It is clear that nanofibrous structures can be used as tools for many applications. It is already known that electrospinning is a highly versatile method of producing nanofibres and recent developments in the technique of electrospinning have led to the development of aligned nanofibres and biphasic, core-sheath fibres which can be used to encapsulate different materials from molecules to cells. Natural extracellular matrix (ECM) contains fibres in both micro and nano-scales and provides a structural scaffold which allows cells to localize, migrate, proliferate and differentiate. Polymer nanofibres can provide the structural cues of ECM. However, current literature gives new hope to further functionalising polymeric nanofibres by using them for drug delivery devices and improving their design to improve control of delivery. By encapsulating active agents within nanofibres (multifunctional nanofibres), a degree of control can be exerted over the release of encapsul! ated agents and therefore, the behaviour of cells can be manipulated for developing effective therapies and is extremely encouraging in the tissue engineering field by combining factors like fibre diameter, alignment and chemicals in new ways. Such multifunctional nanofibre-based systems are already being investigated in vivo. Experiments have shown the significant potential for treatments of disease and engineering of neural and bone tissues. Further, phase III clinical trials of nanofibrous patches for applications in wound treatment were encouraging. Hopefully, clinical applications of these drug delivery devices will follow, to enhance regenerative medicine applications. PMID: 20055102 [PubMed - in process] | | |
| Genetic and biochemical definition of the Hedgehog receptor.
January 10, 2010 at 7:11 AM
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| | Genetic and biochemical definition of the Hedgehog receptor. Genes Dev. 2010 Jan 1;24(1):57-71 Authors: Zheng X, Mann RK, Sever N, Beachy PA Although the transporter-like protein Patched (Ptc) is genetically implicated in reception of the extracellular Hedgehog (Hh) protein signal, a clear definition of the Hh receptor is complicated by the existence of additional Hh-binding proteins and, in Drosophila, by the lack of physical evidence for direct binding of Hh to Ptc. Here we show that activity of Ihog (Interference hedgehog), or of its close relative Boi (Brother of Ihog), is absolutely required for Hh biological response and for sequestration of the Hh protein to limit long-range signaling. We demonstrate that Ihog interacts directly with Ptc, is required for presentation of Ptc on the cell surface, and that Ihog and Ptc are both required for high-affinity Hh binding. On the basis of their joint roles in ligand binding, signal transduction, and receptor trafficking, we conclude that Ihog and Ptc together constitute the Drosophila Hh receptor. PMID: 20048000 [PubMed - indexed for MEDLINE] | | |
| Evaluation of a respiratory assist catheter that uses an impeller within a hollow fiber membrane bundle.
January 10, 2010 at 7:11 AM
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| | Evaluation of a respiratory assist catheter that uses an impeller within a hollow fiber membrane bundle. ASAIO J. 2009 Nov-Dec;55(6):569-74 Authors: Mihelc KM, Frankowski BJ, Lieber SC, Moore ND, Hattler BG, Federspiel WJ Respiratory assist using an intravenous catheter may be a potential treatment for patients suffering from acute or acute-on-chronic lung failure. The objective of this study was to evaluate a novel respiratory catheter that uses an impeller within the fiber bundle to enhance gas exchange efficiency, thus requiring a smaller fiber bundle and insertional size (25 Fr) and permitting simple percutaneous insertion. Bench testing of gas exchange in deionized water was used to evaluate eight impeller designs. The three best performing impeller designs were evaluated in acute studies in four calves (122 + or - 10 kg). Gas exchange increased significantly with increasing impeller rotation rate. The degree of enhancement varied with impeller geometry. The maximum gas exchange efficiency (exchange per unit surface area) for the catheter with the best performing impeller was 529 + or - 20 ml CO(2)/min/m(2) and 513 + or - 21 ml CO(2)/min/m(2) for bench and animal studies, resp! ectively, at a rotation rate of 20,000 rpm. Absolute CO(2) exchange was 37 and 36 ml CO(2)/min, respectively. Active mixing by rotating impellers produced 70% higher gas exchange efficiency than pulsating balloon catheters. The sensitivity of gas exchange to impeller design suggests that further improvements can be made by computational fluid dynamics-based optimization of the impeller. PMID: 19779302 [PubMed - indexed for MEDLINE] | | | |
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