|  |  |  | | | | | TERMSC | | | | | | | | | | | | | | | | | | | E phage gene transfection enhances sensitivity of lung and colon cancer cells to chemotherapeutic agents. Int J Oncol. 2010 Dec;37(6):1503-14 Authors: Rama AR, Prados J, Melguizo C, Ortiz R, Alvarez PJ, Rodríguez-Serrano F, Hita F, Ramos JL, Burgos M, Aranega A The E gene from ΦX174 encodes a membrane protein with a toxic domain that leads to a decrease in the tumour cell growth rate. With the aim of improving the antitumour effect on lung and colon cancer cells of the currently used chemotherapeutic drugs such as gemcitabine, carboplatin and paclitaxel, and 5-fluorouracil (5FU) plus folinic acid (FA) with irinotecan or oxaliplatine, we investigated a new combined therapy using these drugs associated to the transfection of E gene. Our results showed that E gene was able to decrease proliferation rate in A-549 and T-84 cells by inducing apoptotic the mitochondrial pathway. Significantly greater inhibition of proliferation was obtained using drugs in combination with E gene in comparison to single-agent treatments or controls. E gene combined with paclitaxel had the greatest effect on A-549 cells and combined with 5FU/FA/oxaliplatin on T-84 cells. Antitumour mechanisms of the chemotherapeutic drugs were enhanced by E gene, which itself has direct oncolytic effects inducing A-549 and T-84 apoptosis. Our in vitro results indicate that the combined therapy of E gene and cytotoxic drugs may be of potential therapeutic value as a new strategy for patients with advanced lung and colon cancer. PMID: 21042719 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Pretreatment of periosteum with TGF-beta1 in situ enhances the quality of osteochondral tissue regenerated from transplanted periosteal grafts in adult rabbits. Osteoarthritis Cartilage. 2010 Sep;18(9):1183-91 Authors: Olivos-Meza A, Fitzsimmons JS, Casper ME, Chen Q, An KN, Ruesink TJ, O'Driscoll SW, Reinholz GG To compare the efficacy of in situ transforming growth factor-beta1 (TGF-beta1)-pretreated periosteum to untreated periosteum for regeneration of osteochondral tissue in rabbits. PMID: 20633683 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | The continuing evolution of biomaterials. Biomaterials. 2011 Jan;32(1):1-2 Authors: Williams D PMID: 20933267 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Turning human epidermis into pancreatic endoderm. Rev Diabet Stud. 2010;7(2):158-67 Authors: Santamaria P, Rodriguez-Piza I, Clemente-Casares X, Yamanouchi J, Mulero-Perez L, Aasen T, Raya A, Izpisua Belmonte JC Human embryonic stem (hES) cells can be differentiated into pancreatic endoderm structures in vitro. The study was performed to determine whether induced pluripotent stem (iPS) cells can be differentiated into similar structures with comparable efficiency. PMID: 21060974 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Response of engineered cartilage to mechanical insult depends on construct maturity. Osteoarthritis Cartilage. 2010 Dec;18(12):1577-85 Authors: Tan AR, Dong EY, Ateshian GA, Hung CT Injury to articular cartilage leads to degenerative changes resulting in a loss of mechanical and biochemical properties. In engineered cartilage, the injury response of developing constructs is unclear. PMID: 20851200 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Design and synthesis of biomimetic multicomponent all-bone-minerals bionanocomposites. Biomacromolecules. 2010 Oct 11;11(10):2545-9 Authors: Biswas A, Bayer IS, Zhao H, Wang T, Watanabe F, Biris AS We report a simple and novel top-down method based on a drop-casting process for the controlled synthesis of all-bone-minerals biomimetic multicomponent bionanocomposites. Integration of micro- and nanoscale binary features into nanofibrous biocompatible polymer scaffold structures is successfully demonstrated. Compositional control of the constituents of the bionanocomposites resulted in uniform dispersion of hydroxyapatite nanospheres (~100-500 nm) among collagen nanofibers (~100 nm). The composites also present high calcium and oxygen contents and adequate phosphorus compositions comparable to the levels of bone tissues. Our preliminary results open up further possibilities to develop advanced tissue-engineered bionanocomposites for bone grafting. PMID: 20863130 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Identification of molecular markers for articular cartilage. Osteoarthritis Cartilage. 2010 Dec;18(12):1630-8 Authors: Hissnauer TN, Baranowsky A, Pestka JM, Streichert T, Wiegandt K, Goepfert C, Beil FT, Albers J, Schulze J, Ueblacker P, Petersen JP, Schinke T, Meenen NM, Pörtner R, Amling M The aim of the current study was to identify molecular markers for articular cartilage (AC) that can be used as tools for the quality control of tissue engineered (TE) cartilage. PMID: 20950698 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Unravelling the development of the visual cortex: implications for plasticity and repair. J Anat. 2010 Oct;217(4):449-68 Authors: Bourne JA The visual cortex comprises over 50 areas in the human, each with a specified role and distinct physiology, connectivity and cellular morphology. How these individual areas emerge during development still remains something of a mystery and, although much attention has been paid to the initial stages of the development of the visual cortex, especially its lamination, very little is known about the mechanisms responsible for the arealization and functional organization of this region of the brain. In recent years we have started to discover that it is the interplay of intrinsic (molecular) and extrinsic (afferent connections) cues that are responsible for the maturation of individual areas, and that there is a spatiotemporal sequence in the maturation of the primary visual cortex (striate cortex, V1) and the multiple extrastriate/association areas. Studies in both humans and non-human primates have started to highlight the specific neural underpinnings responsible for the maturation of the visual cortex, and how experience-dependent plasticity and perturbations to the visual system can impact upon its normal development. Furthermore, damage to specific nuclei of the visual cortex, such as the primary visual cortex (V1), is a common occurrence as a result of a stroke, neurotrauma, disease or hypoxia in both neonates and adults alike. However, the consequences of a focal injury differ between the immature and adult brain, with the immature brain demonstrating a higher level of functional resilience. With better techniques for examining specific molecular and connectional changes, we are now starting to uncover the mechanisms responsible for the increased neural plasticity that leads to significant recovery following injury during this early phase of life. Further advances in our understanding of postnatal development/maturation and plasticity observed during early life could offer new strategies to improve outcomes by recapitulating aspects of the developmental program in the adult brain. PMID: 20722872 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Prediction of osteoconductive activity of modified potassium fluorrichterite glass-ceramics by immersion in simulated body fluid. J Mater Sci Mater Med. 2010 Nov;21(11):2979-88 Authors: Bhakta S, Pattanayak DK, Takadama H, Kokubo T, Miller CA, Mirsaneh M, Reaney IM, Brook I, van Noort R, Hatton PV Potassium fluorrichterite (KNaCaMg(5)Si(8)O(22)F(2)) glass-ceramics were modified by either increasing the concentration of calcium (GC5) or by the addition of P(2)O(5) (GP2). The stoichiometric composition (GST), GC5 and GP2 were soaked in simulated body fluid (SBF) along with 45S5-type bioglass as a control. After immersion, surface analyses were performed using thin-film X-ray diffraction (TF-XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and Fourier-transform infrared (reflection) spectroscopy (FT-IR). All compositions showed the formation of a calcium phosphate rich surface layer in SBF; GST, GP2 and the bioglass control within 7 days of immersion and GC5 after 14 days. It was concluded that all compositions were likely to be osteoconductive in vivo, with GP2 providing the best performance in terms of the combination of rapid formation of the surface layer and superior mechanical properties. This glass-ceramic system has potential as a load bearing bioceramic for fabrication of medical devices intended for skeletal tissue repair. PMID: 20725768 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Effect of self-assembling peptide, chondrogenic factors, and bone marrow-derived stromal cells on osteochondral repair. Osteoarthritis Cartilage. 2010 Dec;18(12):1608-19 Authors: Miller RE, Grodzinsky AJ, Vanderploeg EJ, Lee C, Ferris DJ, Barrett MF, Kisiday JD, Frisbie DD The goal of this study was to test the ability of an injectable self-assembling peptide (KLD) hydrogel with or without chondrogenic factors (CF) and allogeneic bone marrow stromal cells (BMSCs) to stimulate cartilage regeneration in a full-thickness, critically-sized, rabbit cartilage defect model in vivo. We used CF treatments to test the hypotheses that CF would stimulate chondrogenesis and matrix production by cells migrating into acellular KLD (KLD+CF) or by BMSCs delivered in KLD (KLD+CF+BMSCs). PMID: 20851201 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | The effect of source animal age upon extracellular matrix scaffold properties. Biomaterials. 2011 Jan;32(1):128-36 Authors: Tottey S, Johnson SA, Crapo PM, Reing JE, Zhang L, Jiang H, Medberry CJ, Reines B, Badylak SF Biologic scaffold materials composed of mammalian extracellular matrix (ECM) are commonly used for the repair and reconstruction of injured tissues. An important, but unexplored variable of biologic scaffolds is the age of the animal from which the ECM is prepared. The objective of the present study was to compare the structural, mechanical, and compositional properties of small intestinal submucosa (SIS)-ECM harvested from pigs that differed only in age. Degradation product bioactivity of these ECM materials was also examined. Results showed that there are distinct differences in each of these variables among the various age source ECM scaffolds. The strength and growth factors content of ECM from 3-week-old animals is less than that of ECM harvested from 12, 26 or >52-week-old animals. The elastic modulus of SIS-ECM for 3 week and >52-week-old source was less than that of the 12 and 26 week source. Degradation products from all age source ECMs were chemotactic for perivascular stem cells, with the 12 week source the most potent, while the oldest source caused the greatest increase in proliferation. In summary, distinct differences exist in the mechanical, structural, and biologic properties of SIS-ECM harvested from different aged animals. PMID: 20870285 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Polysaccharide-based polyelectrolyte multilayer surface coatings can enhance mesenchymal stem cell response to adsorbed growth factors. Biomacromolecules. 2010 Oct 11;11(10):2629-39 Authors: Almodóvar J, Bacon S, Gogolski J, Kisiday JD, Kipper MJ It is generally accepted that both surface chemistry and biochemical cues affect mesenchymal stem cell (MSC) proliferation and differentiation. Several growth factors that have strong influences on MSC behavior bind to glycosaminoglycans in interactions that affect their stability and their biochemical activity. The goal of this work was to develop polysaccharide-based polyelectrolyte multilayers (PEMs) to bind and stabilize growth factors for delivery to MSCs. Using the naturally derived polysaccharides chitosan and heparin, PEMs were constructed on gold-coated glass chips, tissue-culture polystyrene (TCPS), and titanium. PEM construction and basic fibroblast growth factor (FGF-2) adsorption to PEMs were evaluated by Fourier transform surface plasmon resonance, X-ray photoelectron spectroscopy, and polarization modulation infrared reflection absorption spectroscopy. The functional response of bone marrow-derived ovine MSCs to FGF-2 on PEM-coated TCPS and titanium was evaluated in vitro, in the presence and absence of adsorbed fibronectin. The effect of FGF-2 dose and presentation on MSC attachment and proliferation was evaluated using low-serum media, over four days. On PEM-coated TCPS, we found that FGF-2 adsorbed to heparin-terminated PEMs with adsorbed fibronectin induces greater cell density and a higher proliferation rate of MSCs than any of the other conditions tested, including delivery of the FGF-2 in solution, at an optimally mitogenic dose. Cell densities on day four were 1.8 times higher when FGF-2 was delivered by adsorption to the PEM than when FGF-2 was delivered in solution. This system represents a promising candidate for the development of surface coatings that can stabilize and potentiate the activity of growth factors for therapeutic applications. Interestingly, the same effects were not observed when FGF-2 was delivered by adsorption to PEMs on titanium. When the polysaccharide-based PEMs were formed on titanium, the proliferative response of ovine MSCs to adsorbed FGF-2 was not as strong as the response to FGF-2 delivered in solution. PMID: 20795698 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Hyperbranched poly(NIPAM) polymers modified with antibiotics for the reduction of bacterial burden in infected human tissue engineered skin. Biomaterials. 2011 Jan;32(1):258-67 Authors: Shepherd J, Sarker P, Rimmer S, Swanson L, MacNeil S, Douglas I The escalating global incidence of bacterial infection, particularly in chronic wounds, is a problem that requires significant improvements to existing therapies. We have developed hyperbranched poly(NIPAM) polymers functionalized with the antibiotics Vancomycin and Polymyxin-B that are sensitive to the presence of bacteria in solution. Binding of bacteria to the polymers causes a conformational change, resulting in collapse of the polymers and the formation of insoluble polymer/bacteria complexes. We have applied these novel polymers to our tissue engineered human skin model of a burn wound infected with Pseudomonas aeruginosa and Staphylococcus aureus. When the polymers were removed from the infected skin, either in a polymer gel solution or in the form of hydrogel membranes, they removed bound bacteria, thus reducing the bacterial load in the infected skin model. These bacteria-binding polymers have many potential uses, including coatings for wound dressings. PMID: 20933276 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Biologic scaffolds for constructive tissue remodeling. Biomaterials. 2011 Jan;32(1):316-9 Authors: Badylak SF, Brown BN, Gilbert TW, Daly KA, Huber A, Turner NJ PMID: 21125721 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Osteoclastic cell behaviors affected by the α-tricalcium phosphate based bone cements. J Mater Sci Mater Med. 2010 Nov;21(11):3019-27 Authors: Oh SA, Lee GS, Park JH, Kim HW Calcium phosphate cements (CPCs) have recently gained great interest as injectable bone substitutes for use in dentistry and orthopedics. α-tricalcium phosphate (α-TCP) is a popularly used precursor powder for CPCs. When mixed with appropriate content of liquid and kept under aqueous conditions, α-TCP dissolves to form a calcium-deficient hydroxyapatite and then hardens to cement. In this study, α-TCP based cement (CP) and its composite cement with chitosan (Ch-CP) were prepared and the osteoclastic responses to the cements and their elution products were evaluated. Preliminary evaluation of the cements revealed that the CP and Ch-CP hardened within ~10 min at an appropriate powder-to-liquid ratio (PL) of 3.0. In addition, CP and Ch-CP were transformed into an apatite phase following immersion in a saline solution. Moreover, the osteoblastic cells were viable on the cements for up to 10 days. Mouse-derived bone marrow cells were isolated and activated with osteoclastic differentiation medium, and the effects of the CP and Ch-CP substrates and their ionic eluants on the osteoclastic activity were investigated. Osteoclastic cells were viable for up to 14 days on both types of cements, maintaining a higher cell growth level than the control culture dish. Multi-nucleated osteoclastic cells that were tartrate-resistant acid phosphatase (TRAP)-positive were clearly observed when cultured on the cement substrates as well as treated with the cement eluants. The TRAP activity was found to be significantly higher in cells influenced by the cement substrates and their eluants with respect to the control culture dish (Ch-CP > CP ≫ control). Overall, the osteoclastic differentiation was highly stimulated by the α-TCP based experimental cements in terms of both the substrate interaction and their elution products. PMID: 20857323 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Tissue-engineered cardiac constructs for cardiac repair. Ann Thorac Surg. 2011 Jan;91(1):320-9 Authors: Miyagawa S, Roth M, Saito A, Sawa Y, Kostin S Several recent basic research studies have described surgical methods for cardiac repair using tissue cardiomyoplasty. This review summarizes recent advances in cardiac repair using bioengineered tissue from the viewpoint of the cardiac surgeon. We conclude that the results of many basic and preclinical studies indicate that bioengineered tissue can be adapted to conventional surgical techniques. However, no clinical studies have yet proved bioengineered tissue is effective as a treatment for human heart failure. Today's cardiac surgeons can look forward to the advent of new techniques to benefit patients who respond poorly to existing treatment for heart failure. PMID: 21172551 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | HIF-2α as a possible therapeutic target of osteoarthritis. Osteoarthritis Cartilage. 2010 Dec;18(12):1552-6 Authors: Saito T, Kawaguchi H Endochondral ossification, a conversion process from nonvascularized and hypoxic cartilage to highly vascularized bone, plays a crucial role in osteoarthritis (OA) development as well as in physiological skeletal growth. We have shown that hypoxia-inducible factor-2α (HIF-2α, encoded by EPAS1) is an extensive regulator of the endochondal ossification process. Here we review the possible signaling network regulating OA development on the axis of HIF-2α. PMID: 20950696 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Do patients with complete transposition of the great arteries and severe pulmonary hypertension benefit from an arterial switch operation? Ann Thorac Surg. 2011 Jan;91(1):181-6 Authors: Fan H, Hu S, Zheng Z, Li S, Zhang Y, Pan X, Liu Y Whether an arterial switch operation benefits patients with transposition of the great arteries and severe pulmonary hypertension (PH) remains controversial. Therefore, we evaluated the relationship between preoperative PH and early and midterm clinical outcomes after an arterial switch procedure. PMID: 21172509 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Adult bone marrow stromal cell-based tissue-engineered aggrecan exhibits ultrastructure and nanomechanical properties superior to native cartilage. Osteoarthritis Cartilage. 2010 Nov;18(11):1477-86 Authors: Lee HY, Kopesky PW, Plaas A, Sandy J, Kisiday J, Frisbie D, Grodzinsky AJ, Ortiz C To quantify the structural characteristics and nanomechanical properties of aggrecan produced by adult bone marrow stromal cells (BMSCs) in peptide hydrogel scaffolds and compare to aggrecan from adult articular cartilage. PMID: 20692354 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Tuning the differentiation of periosteum-derived cartilage using biochemical and mechanical stimulations. Osteoarthritis Cartilage. 2010 Nov;18(11):1528-35 Authors: Kock LM, Ravetto A, van Donkelaar CC, Foolen J, Emans PJ, Ito K In this study, we aim at tuning the differentiation of periosteum in an organ culture model towards cartilage, rich in collagen type II, using combinations of biochemical and mechanical stimuli. We hypothesize that addition of TGF-β will stimulate chondrogenesis, whereas sliding indentation will enhance collagen synthesis. PMID: 20833251 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Cell origin of human mesenchymal stem cells determines a different healing performance in cardiac regeneration. PLoS One. 2011;6(2):e15652 Authors: Gaebel R, Furlani D, Sorg H, Polchow B, Frank J, Bieback K, Wang W, Klopsch C, Ong LL, Li W, Ma N, Steinhoff G The possible different therapeutic efficacy of human mesenchymal stem cells (hMSC) derived from umbilical cord blood (CB), adipose tissue (AT) or bone marrow (BM) for the treatment of myocardial infarction (MI) remains unexplored. This study was to assess the regenerative potential of hMSC from different origins and to evaluate the role of CD105 in cardiac regeneration. Male SCID mice underwent LAD-ligation and received the respective cell type (400.000/per animal) intramyocardially. Six weeks post infarction, cardiac catheterization showed significant preservation of left ventricular functions in BM and CD105(+)-CB treated groups compared to CB and nontreated MI group (MI-C). Cell survival analyzed by quantitative real time PCR for human GAPDH and capillary density measured by immunostaining showed consistent results. Furthermore, cardiac remodeling can be significantly attenuated by BM-hMSC compared to MI-C. Under hypoxic conditions in vitro, remarkably increased extracellular acidification and apoptosis has been detected from CB-hMSC compared to BM and CD105 purified CB-derived hMSC. Our findings suggests that hMSC originating from different sources showed a different healing performance in cardiac regeneration and CD105(+) hMSC exhibited a favorable survival pattern in infarcted hearts, which translates into a more robust preservation of cardiac function. PMID: 21347366 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Discussion. Bioengineered skin constructs and their use in wound healing. Plast Reconstr Surg. 2011 Jan;127 Suppl 1:91S-92S Authors: Veves A PMID: 21200277 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Stem cells in dentistry and medicine: the dentist's role. Dent Today. 2011 Jan;30(1):128, 130-4; quiz 135 Authors: Krasner P, Verlander P Research has shown that teeth are a source of high quality stem cells that may be used for the treatment of medical and dental disease. The discovery that odontogenic tissues are a source of adult stem cells has opened up a new role for dentists in the field of medicine. Dentists are positioned to become one of the key providers of stem cells, and as a result, their linkage with the medical field will become very intimate. Dental stem cells have the potential to be used in the treatment of a full range of oral pathoses. Dentists can be involved in the extraction, collection, and storage of the stem cells from their patients' teeth. Ongoing research suggests that these stem cells will soon be used for dental purposes such as to replace lost bone around teeth, periodontal ligament or dental pulp; treat periodontal disease; and someday even produce new teeth, as well as for medical applications. In order for dentists to fully participate in this new role, they should become aware of the applications, clinical use, and banking of dental stem cells. PMID: 21306072 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Core-sheath-structured fibers with pDNA polyplex loadings for optimal release profile and transfection efficiency as potential tissue engineering scaffolds. Acta Biomater. 2011 Feb 20; Authors: Yang Y, Li X, Cheng L, He S, Zou J, Chen F, Zhang Z Emulsion electrospinning was initially applied to prepare core-sheath structured fibers with the core-loading of pDNA or pDNA polyplexes into fiber sheath of poly(DL-lactide)-poly(ethylene glycol) (PELA). The inoculations of poly(ethylene imine) (PEI) and poly(ethylene glycol) (PEG) were expected to modulate the release profiles, and achieve a balance between the cytotoxicity and transfection efficiency. The core-sheath fibers enhance the structural integrity and biological activity retention of pDNA during the electrospinning process, incubation in release buffer and enzyme digestion. The addition of hydrophilic PEI into fiber matrices accelerates pDNA release, while the encapsulation of pDNA polyplexes within fibers leads no more release after initial burst release. However, a sustained release of pDNA polyplexes has been achieved through PEG incorporation, and the effective release lifetime can be controlled between 6 and 25 d, dependent on the loading amount and molecular weight of PEG. Higher N/P ratios of PEI to DNA result in lower cell attachment ability, and the cell viability is dependent on the effective concentration of pDNA polyplexes released from fibers. While no apparent transfection is detected for pDNA-loaded PELA fibers, PEG inoculations into fibers containing pDNA polyplexes lead over one order of magnitude increase in the transfection efficiency. It is indicated that pDNA polyplexes-loaded fibers with the inoculation of 10% PEG show the best performance in balancing the transfection efficiency and cell viability. It is suggested that electrospun core-sheath fibers integrated with DNA condensation techniques provide potentials for inductive tissue engineering scaffolds to manipulate desired signals at effective levels within the local tissue microenvironment. PMID: 21345386 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | BMP-2 Gene Modified Canine bMSCs Promote Ectopic Bone Formation Mediated by a Nonviral PEI Derivative. Ann Biomed Eng. 2011 Feb 23; Authors: Lü K, Zeng D, Zhang Y, Xia L, Xu L, Kaplan DL, Jiang X, Zhang F The study was to explore the effects of BMP-2 gene modified canine bone marrow stromal cells (bMSCs) mediated by a nonviral PEI derivative (GenEscort™ II) in promoting bone formation in vitro and in vivo. Canine bMSCs were cultured and transfected with plasmids containing bone morphogenetic protein-2 gene (pBMP-2) or enhanced green fluorescent protein gene (pEGFP). Gene transfection conditions were initially optimized by varying GenEscort™ II/plasmid ratios. Osteogenic differentiation of gene modified bMSCs was investigated via alkaline phosphatase (ALP) activity analysis and real-time quantitative PCR (RT-qPCR) analysis in vitro. The bone formation ability of pBMP-2 transfected bMSCs combined with apatite-coated silk scaffolds (mSS) was explored and compared with pEGFP transfected bMSCs/mSS or untreated bMSCs/mSS at 8, 12 weeks after operation. Results showed that gene transfection efficiency reached up to 36.67 ± 4.12% as demonstrated by EGFP expression. ALP staining and activity assay were stronger with pBMP-2 gene transfection, and the mRNA expression of BMP-2, bone sialoprotein (BSP), Runt-related transcription factor 2 (Runx-2), and osteopontin (OPN) up-regulated in bMSCs 3, 6, 9 days in pBMP-2 group. Besides, the tissue-engineered bone complex with pBMP-2 modified bMSCs achieved significantly increased de novo bone formation compared with control groups (p < 0.01). We conclude that pBMP-2 transfection mediated by GenEscort™ II could enhance the osteogenic differentiation of canine bMSCs and promote the ectopic new bone formation in nude mice. GenEscort™ II mediated pBMP-2 gene transfer appears to be a safe and effective nonviral method for gene enhanced bone tissue engineering. PMID: 21347550 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Engineering a stem cell house into a home. Stem Cell Res Ther. 2011 Jan 31;2(1):3 Authors: Gilbert PM, Blau HM ABSTRACT: In the body, tissue homeostasis is established and maintained by resident tissue-specific adult stem cells (aSCs). Through preservation of bidirectional communications with the surrounding niche and integration of biophysical and biochemical cues, aSCs actively direct the regeneration of aged, injured and diseased tissues. Currently, the ability to guide the behavior and fate of aSCs in the body or in culture after prospective isolation is hindered by our poor comprehension of niche composition and the regulation it imposes. Two-and three-dimensional biomaterials approaches permit systematic analysis of putative niche elements as well as screening approaches to identify novel regulatory mechanisms governing stem cell fate. The marriage of stem cell biology with creative bioengineering technology has the potential to expand our basic understanding of stem cell regulation imposed by the niche and to develop novel regenerative medicine applications. PMID: 21345268 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Reliability of Upper Extremity Kinematics While Performing Different Tasks in Individuals With Stroke. J Mot Behav. 2011 Feb 23;:1 Authors: Patterson TS, Bishop MD, McGuirk TE, Sethi A, Richards LG Assessments of upper extremity performance typically include qualitative rather than quantitative measures of functional ability. Kinematic analysis is an objective, discriminative measure that quantifies movement biomechanics; however, the use within the poststroke impaired upper extremity is not well established. The purpose of this study was to examine the reliability of upper extremity kinematics in 18 individuals with stroke and 9 healthy controls. Participants performed reaching and grasping tasks over 2 separate days and metrics included movement time, peak velocity, index of curvature, trunk displacement, maximum aperture, and percentage of the movement cycle where maximum aperture occurred. The results showed moderate to high intraclass correlation and low standard error of measurement values for most variables, demonstrating that kinematic analysis may be a feasible and useful tool to quantify upper extremity movement after stroke. PMID: 21347950 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | How to Get from Here to There: Macrophage Recruitment in Alzheimer's Disease. Curr Alzheimer Res. 2011 Feb 23; Authors: Rezai-Zadeh K, Gate D, Gowing G, Town T Alzheimer's disease (AD) is pathologically defined by presence of intracellular neurofibrillary tangles and extracellular amyloid plaques comprised of amyoid-β (Aβ) peptides. Despite local recruitment of brain microglia to sites of amyloid deposition, these mononuclear phagocytes ultimately fail at restricting β-amyloid plaque formation. On the other hand, it is becoming increasingly clear that professional phagocytes from the periphery possess Aβ clearance aptitude. Yet, in order to harness this beneficial innate immune response, effective strategies must be developed to coax monocytes/macrophages from the periphery into the brain. It has previously been suggested that Aβ 'immunotherapy' clears cerebral Aβ deposits via mononuclear phagocytes, and recent evidence suggests that targeting transforming growth factor-β-Smad 2/3 signaling and chemokine pathways such as Ccr2 impacts blood-to-brain trafficking of these cells in transgenic mouse models of AD. It has also been shown that the fractalkine receptor (Cx3cr1) pathway plays a critical role in chemotaxis of mononuclear phagocytes toward neurons destined for death in AD model mice. In order to translate these basic science findings into AD treatments, a key challenge will be to develop a new generation of pharmacotherapeutics that safely and effectively promote recruitment of peripheral amyloid phagocytes into the AD brain. PMID: 21345166 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | How allograft tissue is regulated. OR Manager. 2010 Dec;26(12):17 Authors: PMID: 21250562 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Electrospun scaffolds of self-assembling peptides with poly(ethylene oxide) for bone tissue engineering. Acta Biomater. 2011 Feb 20; Authors: Brun P, Ghezzo F, Roso M, Danesin R, Palù G, Bagno A, Modesti M, Castagliuolo I, Dettin M Searching for suitable extracellular matrix substitutes, structural, mechanical and biochemical properties have to be considered. Fibrous structures of synthetic or natural polymers received increasing interest as 3D-scaffold for tissue engineering applications: they can be easily produced by electrospinning with different topographical features by changing process parameters. On the other hand, the nanobiotechnology approach suggests to mimic molecular architectures in nature through self-assembling process. In particular self-assembling peptide-based biomaterials have been successfully used as scaffolds for cell growth. In order to join these two strategies, nano-fibrous electrospun scaffolds of hybrid polymer were designed and obtained by mixing poly(ethylene oxide) and self-assembling peptides in aqueous solution. The results of in vitro osteoblast adhesion and proliferation assays on the electrospun scaffolds obtained with different self-assembling peptide sequences are discussed in this paper. PMID: 21345384 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Fat cells reactivate quiescent neuroblasts via TOR and glial insulin relays in Drosophila. Nature. 2011 Feb 23; Authors: Sousa-Nunes R, Yee LL, Gould AP Many stem, progenitor and cancer cells undergo periods of mitotic quiescence from which they can be reactivated. The signals triggering entry into and exit from this reversible dormant state are not well understood. In the developing Drosophila central nervous system, multipotent self-renewing progenitors called neuroblasts undergo quiescence in a stereotypical spatiotemporal pattern. Entry into quiescence is regulated by Hox proteins and an internal neuroblast timer. Exit from quiescence (reactivation) is subject to a nutritional checkpoint requiring dietary amino acids. Organ co-cultures also implicate an unidentified signal from an adipose/hepatic-like tissue called the fat body. Here we provide in vivo evidence that Slimfast amino-acid sensing and Target of rapamycin (TOR) signalling activate a fat-body-derived signal (FDS) required for neuroblast reactivation. Downstream of this signal, Insulin-like receptor signalling and the Phosphatidylinositol 3-kinase (PI3K)/TOR network are required in neuroblasts for exit from quiescence. We demonstrate that nutritionally regulated glial cells provide the source of Insulin-like peptides (ILPs) relevant for timely neuroblast reactivation but not for overall larval growth. Conversely, ILPs secreted into the haemolymph by median neurosecretory cells systemically control organismal size but do not reactivate neuroblasts. Drosophila thus contains two segregated ILP pools, one regulating proliferation within the central nervous system and the other controlling tissue growth systemically. Our findings support a model in which amino acids trigger the cell cycle re-entry of neural progenitors via a fat-body-glia-neuroblasts relay. This mechanism indicates that dietary nutrients and remote organs, as well as local niches, are key regulators of transitions in stem-cell behaviour. PMID: 21346761 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Glyoxal Crosslinking of Cell-Seeded Chitosan/Collagenn Hydrogels for Bone Regeneration. Acta Biomater. 2011 Feb 20; Authors: Wang L, Stegemann JP Chitosan and collagen are natural biomaterials that have been used extensively in tissue engineering, both separately and as composite materials. Most methods to fabricate chitosan/collagen composites use freeze drying and chemical crosslinking to create stable porous scaffolds, which subsequently can be seeded with cells. In this study, we directly embedded human bone marrow stem cells (hBMSC) in chitosan/collagen materials by initiating gelation using β-glycerophosphate at physiological temperature and pH. We further examined the use of glyoxal, a dialdehyde with relatively low toxicity, to crosslink these materials and characterized the resulting changes in matrix and cell properties. The cytocompatibility of glyoxal and the crosslinked gels were investigated in terms of hBMSC metabolic activity, viability, proliferation, and osteogenic differentiation. These studies revealed that glyoxal was cytocompatible at concentrations below about 1 mM for periods of exposure up to 15 h, though the degree of cell spreading and proliferation were dependent on matrix composition. Glyoxal-crosslinked matrices were stiffer and compacted less than uncrosslinked controls. It was further demonstrated that hBMSC can attach and proliferate in 3D matrices composed of 50/50 chitosan/collagen, and that these materials supported osteogenic differentiation in response to stimulation. Such glyoxal-crosslinked chitosan/collagen composite materials may find utility as cell delivery vehicles for enhancing the repair of bone defects. PMID: 21345389 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Cell fate conversion by mRNA. Stem Cell Res Ther. 2011 Feb 9;2(1):5 Authors: Li M, Sancho-Martinez I, Belmonte JC ABSTRACT: Recent development of a synthetic mRNA-based technology for efficient reprogramming to pluripotency and cell fate conversion without any modification to the genome has generated great interest among researchers and clinicians alike. It is hoped that this technology could contribute to unmet needs on several fronts of regenerative medicine, including mechanistic study of reprogramming, generation of safe induced pluripotent stem cells suitable for clinical applications, and derivation of desired cell types for cell-replacement therapy. We will discuss the technological advancements made by this synthetic mRNA methodology, its implications, as well as the challenges that lie ahead in the field of regenerative medicine. PMID: 21345255 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Evidence for mesenchymal-epithelial transition associated with mouse hepatic stem cell differentiation. PLoS One. 2011;6(2):e17092 Authors: Li B, Zheng YW, Sano Y, Taniguchi H Mesenchymal-epithelial transition events are related to embryonic development, tissue construction, and wound healing. Stem cells are involved in all of these processes, at least in part. However, the direct evidence of mesenchymal-epithelial transition associated with stem cells is unclear. To determine whether mesenchymal-epithelial transition occurs in liver development and/or the differentiation process of hepatic stem cells in vitro, we analyzed a variety of murine liver tissues from embryonic day 11.5 to adults and the colonies derived from hepatic stem/progenitor cells isolated with flow cytometry. The results of gene expression, immunohistochemistry and Western blot showed that as liver develops, the expression of epithelial markers such as Cytokeratin18 and E-cadherin increase, while expression of mesenchymal markers such as vimentin and N-cadherin decreased. On the other hand, in freshly isolated hepatic stem cells, the majority of cells (65.0%) co-express epithelial and mesenchymal markers; this proportion is significantly higher than observed in hematopoietic cells, non-hematopoietic cells and non-stem cell fractions. Likewise, in stem cell-derived colonies cultured over time, upregulation of epithelial genes (Cytokeratin-18 and E-cadherin) occurred simultaneously with downregulation of mesenchymal genes (vimentin and Snail1). Furthermore, in the fetal liver, vimentin-positive cells in the non-hematopoietic fraction had distinct proliferative activity and expressed early the hepatic lineage marker alpha-fetoprotein. CONCLUSION: Hepatic stem cells co-express mesenchymal and epithelial markers; the mesenchymal-epithelial transition occurred in both liver development and differentiation of hepatic stem/progenitor cells in vitro. Besides as a mesenchymal marker, vimentin is a novel indicator for cell proliferative activity and undifferentiated status in liver cells. PMID: 21347296 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Investigation of Cell-Substrate Interactions by Focused Ion Beam (FIB) Preparation and Scanning Electron Microscopy (SEM). Acta Biomater. 2011 Feb 20; Authors: Friedmann A, Hoess A, Cismak A, Heilmann A Cell-substrate interactions, which are an important issue in tissue engineering, are studied by using focused ion beam (FIB) milling and scanning electron microscopy (SEM) investigations. Sample cross-sections are generated on predefined positions (target preparation), to investigate the interdependency of growing cells with the substrate material. The experiments focus on two cell culturing systems, hepatocytes (HepG2) on nanoporous aluminum oxide (alumina) membranes and mouse fibroblasts (L929) as well as primary nerve cells on silicon chips with microneedles. On these soft/hard hybrid systems, cross-sections cannot be prepared by conventional techniques like microtomy. Morphological investigations of hepatocytes growing on nanoporous alumina membranes demonstrate that there is an ingrowth of microvilli from the cell surfaces into porous membranes having pore diameters larger than 200 nm. Furthermore, at various cell cultures on the microneedle arrays, the contact between the cells and the microneedles can be observed with high resolution. Based on FIB milled cross-sections and SEM micrographs, it can be clearly distinguished between cells which are only in contact with microneedles and cells which are penetrated by microneedles. Especially, target preparation of biological samples with FIB technique offers the possibility to prepare not only soft material but also hybrid samples (soft/hard materials). Followed by high resolution imaging with SEM, new insights into cell surface interactions can be received. PMID: 21345385 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Osteoblast Connexin43 Modulates Skeletal Architecture by Regulating Both Arms of Bone Remodeling. Mol Biol Cell. 2011 Feb 23; Authors: Watkins M, Grimston SK, Norris JY, Guillotin B, Shaw A, Beniash E, Civitelli R Connexin43 (Cx43) has an important role in skeletal homeostasis, and Cx43 gene (Gja1) mutations have been linked to oculodentodigital dysplasia (ODDD), a human disorder characterized by prominent skeletal abnormalities. To determine the function of Cx43 at early steps of osteogenesis and its role in the ODDD skeletal phenotype, we have used the Dermo1 promoter to drive Gja1 ablation or induce an ODDD mutation in the chondro-osteogenic linage. Both Gja1 null and ODDD mutant mice develop age-related osteopenia, primarily due to a progressive enlargement of the medullary cavity and cortical thinning. This phenotype is the consequence of a high bone turnover state, with increased endocortical osteoclast mediated bone resorption and increased periosteal bone apposition. Increased bone resorption is a non-cell autonomous defect, caused by exuberant stimulation of osteoclastogenesis by Cx43-deficient bone marrow stromal cells, via decreased Opg production. The latter is part of a broad defect in osteoblast differentiation and function, which also results in abnormal structural and material properties of bone leading to decreased resistance to mechanical load. Thus, Cx43 in osteogenic cells is a critical regulator of both arms of the bone remodeling cycle, its absence causing structural changes remindful of aged or disused bone. PMID: 21346198 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | A modified technique for partial pneumonectomy in the mouse. J Invest Surg. 2011;24(2):81-6 Authors: Jackson SR, Williams GN, Lee J, Baer JF, Warburton D, Driscoll B ABSTRACT Background: Partial pneumonectomy (PNX) in mice results in compensatory growth in the remaining lung and is a useful model for lung repair. However, common pitfalls to the technique present a challenge for researchers. A complete description of murine PNX is thus provided, with a modification that, in our hands, enhanced animal survival. Materials and Methods: 10 ± 2 weeks old mice were anesthetized using 5% inhalational isoflurane via tracheotomy. Mechanical ventilation was provided using a Harvard Model 687 ventilator. In a procedure optimized to be performed in ≤20 min, left lateral thoracotomy was used to access to the left lung, which was grasped with a blunt forceps just distal to the hilum and clipped using a single 5-mm neuro clip. The left lung was resected, leaving a small rim of lung tissue immediately adjacent to the clip. The thoracotomy was closed, and while anesthesia was titrated, sterile saline was injected subcutaneously to replace insensible fluid losses. Upon return of spontaneous breaths, the trachea was decannulated, and the tracheotomy was closed. Results: Even when performed by a single operator, this modified technique produced a survival rate of >85% during the procedure and >90% up to seven days postoperatively in wild-type C57BL/6J mice. Conclusions: Minimizing the time required to perform left lobe pneumonectomy is critical for animal survival. Using a 5-mm neuro clip, rather than silk suture, to isolate the lobe streamlines the procedure, helps reduce cardiac arrythmia, and results in significantly increased rates of intraoperative and immediate postoperative survival. PMID: 21345008 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Template for skin regeneration. Plast Reconstr Surg. 2011 Jan;127 Suppl 1:60S-70S Authors: Yannas IV, Orgill DP, Burke JF Advances in critical care allowed survival of large total body surface burn patients in the 1970s, spawning the development of artificial skin for burn victims. Lack of dermis resulted in severe scarring and contractures. The physicochemical properties that are critical to dermal regeneration have subsequently been described, and a dermal regeneration template has been developed. PMID: 21200274 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Determining Cell Seeding Dosages for Tissue Engineering Human Pulmonary Valves. J Surg Res. 2010 Dec 23; Authors: Frank BS, Toth PB, Wells WK, McFall CR, Cromwell ML, Hilbert SL, Lofland GK, Hopkins RA BACKGROUND: This study examines in vitro seeding of decellularized human pulmonary valves (hPVs) with human valve interstitial cells (hVICs) isolated from unrelated donor aortic valve leaflets. An assay was developed to assess seeding using precut uniform sized biopsies from whole hPVs for sequential evaluation of seeding efficiency, proliferation, and migration. MATERIALS AND METHODS: Scaffolds for seeding were created from decellularized hPVs using a reciprocating osmolality, double detergent, enzyme, multiple solvent protocol. hVICs seeded decellularized leaflet and sinus wall scaffolds were incubated in either static or cyclic pressure bioreactors. Low, medium, and high initial cell seeding "dosing" densities were assayed at subsequent three time points, using eight replicates each (n = 576 biopsies including manufactured scaffold controls). Metabolically viable seeded cells were quantified by MTT assay. Histology defined cell locations and morphology. RESULTS: After 24 h of static seeding with 2.5 × 10(5) cells (medium dose), 100 ± 13 cells/mm(2) (2.5%) attached to leaflets, compared with 193 ± 21 cells/mm(2) (8%) for sinuses. Subsequent 4 d in static culture yielded 894 ± 84 and 838 ± 50 cells/mm(2)versus pulsatile culture yielding 80 ± 12 and 79 ± 12 cells/mm(2) for leaflet and sinus, respectively. However, 76.0% ± 12.2% of cells in leaflets in the pulsatile bioreactor were subsurface as compared to 21.4% ± 3.9% in statically cultured leaflets (P < 0.001). CONCLUSION: Different seeding modes suggest a tradeoff between surface proliferation resulting in higher absolute cell numbers for static seeding versus fewer cells in a cyclic pressure bioreactor but with a greater percentage having migrated into the matrix. The medium seeding dose determined to be optimal is actually feasible for tissue engineering heart valves, and can be achieved by fairly traditional cell amplification methods. PMID: 21345451 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | State of the art in topical wound-healing products. Plast Reconstr Surg. 2011 Jan;127 Suppl 1:44S-59S Authors: Fan K, Tang J, Escandon J, Kirsner RS Chronic wounds represent a significant medical burden. Such wounds fail to normally progress through the stages of healing, often complicated by a proinflammatory milieu caused by increased proteinases, hypoxia, and bacterial burden. As a result, several modalities, such as dressings, antimicrobials, growth factors, and human skin substitutes, have been devised in an attempt to correct the chronic wound environment. This review addresses these modalities with a focus on evidence and randomized controlled trials. PMID: 21200273 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Discussion. Template for skin regeneration. Plast Reconstr Surg. 2011 Jan;127 Suppl 1:71S-74S Authors: Janis JE, Steinberg JS PMID: 21200275 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Controlled Release of IGF-1 and HGF from a Biodegradable Polyurethane Scaffold. Pharm Res. 2011 Feb 23; Authors: Nelson DM, Baraniak PR, Ma Z, Guan J, Mason NS, Wagner WR PURPOSE: Biodegradable elastomers, which can possess favorable mechanical properties and degradation rates for soft tissue engineering applications, are more recently being explored as depots for biomolecule delivery. The objective of this study was to synthesize and process biodegradable, elastomeric poly(ester urethane)urea (PEUU) scaffolds and to characterize their ability to incorporate and release bioactive insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF). METHODS: Porous PEUU scaffolds made from either 5 or 8 wt% PEUU were prepared with direct growth-factor incorporation. Long-term in vitro IGF-1 release kinetics were investigated in saline or saline with 100 units/ml lipase to simulate in vivo degradation. Cellular assays were used to confirm released IGF-1 and HGF bioactivity. RESULTS: IGF-1 release into saline occurred in a complex multi-phasic manner for up to 440 days. Scaffolds generated from 5 wt% PEUU delivered protein faster than 8 wt% scaffolds. Lipase-accelerated scaffold degradation led to delivery of >90% protein over 9 weeks for both polymer concentrations. IGF-1 and HGF bioactivity in the first 3 weeks was confirmed. CONCLUSIONS: The capacity of a biodegradable elastomeric scaffold to provide long-term growth-factor delivery was demonstrated. Such a system might provide functional benefit in cardiovascular and other soft tissue engineering applications. PMID: 21347565 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Porosity and Pore Size Regulate the Degradation Product Profile of Polylactide. Biomacromolecules. 2011 Feb 23; Authors: Odelius K, Höglund A, Kumar S, Hakkarainen M, Ghosh AK, Bhatnagar N, Albertsson AC Porosity and pore size regulated the degradation rate and the release of low molar mass degradation products from porous polylactide (PLA) scaffolds. PLA scaffolds with porosities above 90% and different pore size ranges were subjected to hydrolytic degradation and compared to their solid analog. The solid film degraded fastest and the degradation rate of the porous structures decreased with decreasing pore size. Degradation products were detected earlier from the solid films compared to the porous structures as a result of the additional migration path within the porous structures. An intermediate degradation rate profile was observed when the pore size range was broadened. The morphology of the scaffolds changed during hydrolysis where the larger pore size scaffolds showed sharp pore edges and cavities on the scaffold surface. In the scaffolds with smaller pores, the pore size decreased during degradation and a solid surface was formed on the top of the scaffold. Porosity and pore size, thus, influenced the degradation and the release of degradation products that should be taken into consideration when designing porous scaffolds for tissue engineering. PMID: 21344847 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The effect of degradable polymer surfaces on co-cultures of monocytes and smooth muscle cells. Biomaterials. 2011 Feb 21; Authors: McBane JE, Battiston KG, Wadhwani A, Sharifpoor S, Labow RS, Santerre JP Strategies to optimize biomaterial chemistry for applications in vascular tissue engineering attempt to promote endothelial and smooth muscle cell recruitment into porous material constructs. The primary objective is to facilitate relevant tissue formation in a wound healing versus pro-inflammatory manner. The present work investigated the interactive co-cellular response of human monocytes and human vascular smooth muscle cells (VSMCs) with a novel degradable, polar/hydrophobic/ionic (D-PHI) polyurethane and compared it to a commercially available biomaterial, poly-lactic-glycolic acid (PLGA) as well as tissue culture polystyrene (TCPS). D-PHI triggered a smaller pro-inflammatory response (acid phosphatase, esterase, tumor necrosis factor-α) at later time points (>14 d) than PLGA suggesting that monocytes may be transitioning to a more wound-healing phenotype on the D-PHI surface. When D-PHI was coated with collagen, monocyte cell attachment did not differ with the native D-PHI; however, PLGA showed significant differences between collagen coated versus uncoated surfaces. There were more VSMCs and monocytes attached in co-culture to D-PHI when compared to PLGA. Co-cultures on D-PHI released more IL-10 (anti-inflammatory) than monocytes cultured alone, while the VSMCs retained the expression of its marker protein calponin. Together the above data suggest that co-culturing monocytes with VSMCs may aid in stimulating the attachment of VSMCs to D-PHI while eliciting the desired functional phenotypes for both monocytes (i.e. low inflammation based on IL-10 values) and VSMCs (expressing calponin, a marker of contractility). Moreover, the results of this study demonstrated that D-PHI performed equally or better to PLGA in terms of the assayed biological parameters. PMID: 21345489 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
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