|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | Adult human articular chondrocytes in a microcarrier-based culture system: expansion and redifferentiation. J Orthop Res. 2010 Oct 18; Authors: Schrobback K, Klein TJ, Schuetz M, Upton Z, Leavesley DI, Malda J Expanding human chondrocytes in vitro while maintaining their ability to form cartilage remains a key challenge in cartilage tissue engineering. One promising approach to address this is to use microcarriers as substrates for chondrocyte expansion. While microcarriers have shown beneficial effects for expansion of animal and ectopic human chondrocytes, their utility has not been determined for freshly isolated adult human articular chondrocytes. Thus, we investigated the proliferation and subsequent chondrogenic differentiation of these clinically relevant cells on porous gelatin microcarriers and compared them to those expanded using traditional monolayers. Chondrocytes attached to microcarriers within 2 days and remained viable over 4 weeks of culture in spinner flasks. Cells on microcarriers exhibited a spread morphology and initially proliferated faster than cells in monolayer culture, however, with prolonged expansion they were less proliferative. Cells expanded for 1 month and enzymatically released from microcarriers formed cartilaginous tissue in micromass pellet cultures, which was similar to tissue formed by monolayer-expanded cells. Cells left attached to microcarriers did not exhibit chondrogenic capacity. Culture conditions, such as microcarrier material, oxygen tension, and mechanical stimulation require further investigation to facilitate the efficient expansion of clinically relevant human articular chondrocytes that maintain chondrogenic potential for cartilage regeneration applications. © 2010 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 9999:XX-XX, 2010. PMID: 20957734 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Temporal Gene Expression Profiling during Rat Femoral Marrow Ablation-Induced Intramembranous Bone Regeneration. PLoS One. 2010;5(10): Authors: Wise JK, Sena K, Vranizan K, Pollock JF, Healy KE, Hughes WF, Sumner DR, Virdi AS Enhanced understanding of differential gene expression and biological pathways associated with distinct phases of intramembranous bone regeneration following femoral marrow ablation surgery will improve future advancements regarding osseointegration of joint replacement implants, biomaterials design, and bone tissue engineering. A rat femoral marrow ablation model was performed and genome-wide microarray data were obtained from samples at 1, 3, 5, 7, 10, 14, 28, and 56 days post-ablation, with intact bones serving as controls at Day 0. Bayesian model-based clustering produced eight distinct groups amongst 9,062 significant gene probe sets based on similar temporal expression profiles, which were further categorized into three major temporal classes of increased, variable, and decreased expression. Osteoblastic- and osteoclastic-associated genes were found to be significantly expressed within the increased expression groups. Chondrogenesis was not detected histologically. Adipogenic marker genes were found within variable/decreased expression groups, emphasizing that adipogenesis was inhibited during osteogenesis. Differential biological processes and pathways associated with each major temporal group were identified, and significantly expressed genes involved were visually represented by heat maps. It was determined that the increased expression group exclusively contains genes involved in pathways for matrix metalloproteinases (MMPs), Wnt signaling, TGF-β signaling, and inflammatory pathways. Only the variable expression group contains genes associated with glycolysis and gluconeogenesis, the notch signaling pathway, natural killer cell mediated cytotoxicity, and the B cell receptor signaling pathway. The decreased group exclusively consists of genes involved in heme biosynthesis, the p53 signaling pathway, and the hematopoietic cell lineage. Significant biological pathways and transcription factors expressed at each time point post-ablation were also identified. These data present the first temporal gene expression profiling analysis of the rat genome during intramembranous bone regeneration induced by femoral marrow ablation. PMID: 20957030 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | [Methods of BMP immobilization and evaluation for Ti-based dental implant surface modification.] Beijing Da Xue Xue Bao. 2010 Oct 18;42(5):604-607 Authors: Ren XS, Wei SC, Su XD Ti-based biomaterial has been widely used as dental and bone implant material although its bioactivity still needs improvement especially for dental implant. The bone morphogenetic proteins(BMPs) bound to Ti-based materials will attract the mesenchymal stem cells to differentiate into osteoblast cells, which benefits the response to the protein-material surface, and finally leads to new bone formation. Several methods including physically mixing, coating, plasma immobilization and cross-linking were used to investigate how BMPs bind to Ti-based biomaterials. The latest research papers are focused on the structure and function of BMPs, and the methods to bind BMPs to Ti-based biomaterial and the evaluation methods after protein immobilization are reviewed in this paper. PMID: 20957023 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Mandibular segmental defect regenerated with macroporous biphasic calcium phosphate, collagen membrane, and bone marrow graft in dogs. Arch Otolaryngol Head Neck Surg. 2010 Oct;136(10):971-8 Authors: Jégoux F, Goyenvalle E, Cognet R, Malard O, Moreau F, Daculsi G, Aguado E OBJECTIVE: To reconstruct segmental mandibulectomy using calcium phosphate ceramics and collagen membrane with a delayed bone marrow grafting in experimental animals. DESIGN: Defects of segmental mandibulectomy were filled with calcium phosphate granules and wrapped with a collagen membrane in 4 dogs and left empty as a control in 2 dogs. Two months later, a bone marrow graft was injected into the center of the implants. Animals were humanely killed after a 16-week delay. SUBJECTS: Six adult beagles were included in this study. INTERVENTION: Segmental mandibulectomy. MAIN OUTCOME MEASURE: Bone ingrowth and material resorption in the reconstructed segment. RESULTS: Successful osseous colonization bridged the whole length of the defects. The good new bone formation at the center and the periosteum-like formation at the periphery suggest the osteoinductive role of the bone marrow graft and the healing scaffold role of the membrane. CONCLUSIONS: This model succeeded in regenerating a large segmental defect in the mandible. An investigation with a postimplantation radiation delivery schedule is required with the use of this model, which should be considered as a preclinical study for a bone tissue engineering approach in patients with cancer-related bone defects. PMID: 20956742 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Bladder tissue engineering. Urol Clin North Am. 2010 Nov;37(4):593-9 Authors: Stanasel I, Mirzazadeh M, Smith JJ The bladder can lose the ability to store and empty effectively as a result of numerous conditions. When conservative methods to maximize patient safety and quality of life fail, surgical reconstruction of the bladder is usually considered. Augmentation cystoplasty can be performed with the use of the small bowel, large bowel, or less often, stomach. An alternative approach, tissue engineering, identifies the body's own potential for regeneration and supports this propensity with appropriate raw materials and growth factors so that the body's original structure and function may be restored. Tissue engineering can involve the use of a scaffold or matrix alone or of cell-seeded matrices. Harvesting cells and culturing them has become an important tool in tissue engineering. Multiple possibilities for sources of cells have been investigated, including stem cells and differentiated cells from organs other than the bladder; however, to date, autologous bladder cells remain the gold standard for culture and seeding. PMID: 20955910 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Preparation and chemical and biological characterization of a pectin/chitosan polyelectrolyte complex scaffold for possible bone tissue engineering applications. Int J Biol Macromol. 2010 Oct 15; Authors: Coimbra P, Ferreira P, de Sousa HC, Batista P, Rodrigues MA, Correia IJ, Gil MH In this work, porous scaffolds obtained from the freeze-drying of pectin/chitosan polyelectrolyte complexes were prepared and characterized by FTIR, SEM and weight loss studies. Additionally, the cytotoxicity of the prepared scaffolds was evaluated in vitro, using human osteoblast cells. The results obtained showed that cells adhered to scaffolds and proliferated. The study also confirmed that the degradation by-products of pectin/chitosan scaffold are noncytotoxic. PMID: 20955729 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | CELL-BASED VASCULARIZATION STRATEGIES FOR SKIN TISSUE ENGINEERING. Tissue Eng Part B Rev. 2010 Oct 18; Authors: Hendrickx B, Vranckx J, Luttun A Providing a blood-vascular network to promote survival and integration of cells in thick dermal substitutes for application in full-thickness wounds is quintessential for the successful outcome of skin tissue engineering (STE). Nevertheless, promoting vascularization also represents a critical bottleneck in today's STE practice. Several cell types have been considered and tested, mostly in preclinical studies, to increase vascularization. When the clinical situation allows delayed reconstruction of the defect, an autologous approach is preferable, while in acute cases allogeneic therapy is needed. In both cases, the cells should be harvested with minimal donor site morbidity and should be available in large amounts and safe in terms of tumor formation and transmission of animal diseases. Here, we outline the different mechanisms of cell-based vascularization and subsequently elaborate in more detail on the candidate cell types and their pro's and con's in terms of clinical application and regulation of the wound healing process. PMID: 20954829 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Nanoscaffold based stem cell regeneration therapy: recent advancement and future potential. Expert Opin Biol Ther. 2010 Oct 18; Authors: Prakash S, Khan A, Paul A Importance of the field: Over the past years, extensive research has been directed towards tissue engineering using conventional scaffolds. In-depth studies in this field have led to the realization that in vivo cells interact with the extracellular matrix, composed of nanofibers at sub-micron scale, which not only provides the mechanical support to the cells but also plays a key role in regulation of cellular behavior. This has led to the development of nanofibrous scaffold (NFS) technology which in combination with stem cells is emerging as an important tool in the development of tissue engineering and regenerative medicine. Areas covered in this review: This review summarizes the three methods of nanofibrous scaffold preparation and provides a state-of-the-art update on the recent advancement in the use of nanoscaffolds in stem cell regeneration therapy. What the reader will gain: The review gives the reader an insight on nanoscaffold based therapy methods, such as how these scaffolds can potentially be designed and used in successful development of stem cell based therapies. Take home message: NFS technology when coupled with stem cells and exploited in the right way has a strong potential of being used in stem cell based regenerative medicine. PMID: 20954792 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Indirect rapid prototyping of biphasic calcium phosphate scaffolds as bone substitutes: influence of phase composition, macroporosity and pore geometry on mechanical properties. J Mater Sci Mater Med. 2010 Oct 15; Authors: Schumacher M, Deisinger U, Detsch R, Ziegler G While various materials have been developed for bone substitute and bone tissue engineering applications over the last decades, processing techniques meeting the high demands of scaffold shaping are still under development. Individually adapted and mechanically optimised scaffolds can be derived from calcium phosphate (CaP-) ceramics via rapid prototyping (RP). In this study, porous ceramic scaffolds with a periodic pattern of interconnecting pores were prepared from hydroxyapatite, β-tricalcium phosphate and biphasic calcium phosphates using a negative-mould RP technique. Moulds predetermining various pore patterns (round and square cross section, perpendicular and 60° inclined orientation) were manufactured via a wax printer and subsequently impregnated with CaP-ceramic slurries. Different pore patterns resulted in macroporosity values ranging from about 26.0-71.9 vol% with pore diameters of approximately 340 μm. Compressive strength of the specimens (1.3-27.6 MPa) was found to be mainly influenced by the phase composition as well as the macroporosity, both exceeding the influence of the pore geometry. A maximum was found for scaffolds with 60 wt% hydroxyapatite and 26.0 vol% open porosity. It has been shown that wax ink-jet printing allows to process CaP-ceramic into scaffolds with highly defined geometry, exhibiting strength values that can be adjusted by phase composition and pore geometry. This strength level is within and above the range of human cancellous bone. Therefore, this technique is well suited to manufacture scaffolds for bone tissue engineering. PMID: 20953674 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Xenogenic Extracellular Matrices as Potential Biomaterials for Interposition Grafting in Urological Surgery. J Urol. 2010 Oct 15; Authors: Davis NF, McGuire BB, Callanan A, Flood HD, McGloughlin TM PURPOSE:: The field of tissue engineering focuses on developing strategies for reconstructing injured, diseased, and congenitally absent tissues and organs. During the last decade urologists have benefited from remodeling and regenerative properties of bioscaffolds derived from xenogenic extracellular matrices. We comprehensively reviewed the current literature on structural and functional characteristics of xenogenic extracellular matrix grafting since it was first described in urological surgery. We also reviewed the clinical limitations, and assessed the potential for safe and effective urological application of extracellular matrix grafting in place of autogenous tissue. MATERIALS AND METHODS:: We performed literature searches for English language publications using the PubMed® and MEDLINE® databases. Keywords included "xenogenic," "extracellular matrix" and "genitourinary tract applications." A total of 112 articles were scrutinized, of which 50 were suitable for review based on clinical relevance and importance of content. RESULTS:: Since the mid 1990s xenogenic extracellular matrices have been used to successfully treat a number of pathological conditions that affect the upper and lower genitourinary tract. They are typically prepared from porcine organs such as small intestine and bladder. These organs are harvested and subjected to decellularization and sterilization techniques before surgical implantation. Bioinductive growth factors that are retained during the preparation process induce constructive tissue remodeling as the extracellular matrix is simultaneously degraded and excreted. However, recent documented concerns over durability, decreased mechanical strength and residual porcine DNA after preparation techniques have temporarily hampered the potential of extracellular matrices as a reliable replacement for genitourinary tract structures. CONCLUSIONS:: Extracellular matrices are a useful alternative for successfully treating a number of urological conditions that affect the genitourinary tract. However, clinical concerns regarding mechanical limitations and biosafety need to be addressed before their long-term role in reconstructive urological surgery can be clearly established. PMID: 20952029 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Preparation of 3D scaffolds in the SiO(2)-P(2)O(5) system with tailored hierarchical meso-macroporosity. Acta Biomater. 2010 Oct 14; Authors: García A, Izquierdo-Barba I, Colilla M, Laorden CL, Vallet-Regí M Herein we report for the first time the synthesis of three dimensional scaffolds in the binary system SiO(2)-P(2)O(5) exhibiting different scales of porosity: i) highly ordered mesopores with diameters of ca. 4 nm; ii) macropores with diameters in the 30-80 μm range with interconnections of ca. 2-4 and 8-9 μm and iii) ultra-large pore macropores of ca. 400 μm. The hierarchical porosity of the resulting scaffolds makes them suitable for bone tissue engineering applications. The chemical nature and mesoporosity of these matrices would allow these scaffolds to act as local controlled delivery systems of biologically active molecules such as certain drugs to treat bone pathologies. The synthetic method consists in the combination of a single-step sol-gel route in the presence of a surfactant as mesostructure directing agent and a biomacromolecular polymer such as methylcellulose as macrostructure template followed by rapid prototyping technique. An exhaustive study of the aging process as well as of the rheological properties of the slurry after methylcellulose addition has been carried out to obtain hierarchical meso-macroporosity. This study allows establishing the time period in which the slurry presents appropriate viscosity to be extruded during the rapid prototyping once the ink is prepared. The setting up of this manufacture process at the laboratory level is important from the industrial point of view when the large-scale production of scaffolds for bone tissue repair and regeneration is targeted. PMID: 20951843 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Evaluation of gel spun silk-based biomaterials in a murine model of bladder augmentation. Biomaterials. 2010 Oct 14; Authors: Mauney JR, Cannon GM, Lovett ML, Gong EM, Di Vizio D, Gomez P, Kaplan DL, Adam RM, Estrada CR Currently, gastrointestinal segments are considered the gold standard for bladder reconstructive procedures. However, significant complications including chronic urinary tract infection, metabolic abnormalities, urinary stone formation, bowel dysfunction, and secondary malignancies are associated with this approach. Biomaterials derived from silk fibroin may represent a superior alternative due their robust mechanical properties, biodegradable features, and processing plasticity. In the present study, we evaluated the efficacy of a gel spun silk-based matrix for bladder augmentation in a murine model. Over the course of 70 d implantation period, H&E and Masson's trichrome (MTS) analysis revealed that silk matrices were capable of supporting both urothelial and smooth muscle regeneration at the defect site. Prominent uroplakin and contractile protein expression (α-actin, calponin, and SM22α) was evident by immunohistochemical analysis demonstrating maturation of the reconstituted bladder wall compartments. Gel spun silk matrices also elicited a minimal acute inflammatory reaction following 70 d of bladder integration, in contrast to parallel assessments of small intestinal submucosa (SIS) and poly-glycolic acid (PGA) matrices which routinely promoted evidence of fibrosis and chronic inflammatory responses. Voided stain on paper analysis revealed that silk augmented animals displayed similar voiding patterns in comparison to non surgical controls by 42 d of implantation. In addition, cystometric evaluations of augmented bladders at 70 d post-op demonstrated that silk scaffolds supported significant increases in bladder capacity and voided volume while maintaining similar degrees of compliance relative to the control group. These results provide evidence for the utility of gel spun silk-based matrices for functional bladder tissue engineering applications. PMID: 20951426 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Effects of fibroblast growth factor-2 on the expression and regulation of chemokines in human dental pulp cells. J Endod. 2010 Nov;36(11):1824-30 Authors: Kim YS, Min KS, Jeong DH, Jang JH, Kim HW, Kim EC BACKGROUND: Fibroblast growth factor-2 (FGF-2) participates in both hematopoiesis and osteogenesis; however, the effects of FGF-2 on chemokines during odontoblastic differentiation have not been reported. This study investigated whether human dental pulp cells (HDPCs) treated with FGF-2 could express chemokines during differentiation into odontoblastic cells and sought to identify its underlying mechanism of action. METHODS: To analyze differentiation, we measured alkaline phosphatase (ALP) activity, calcified nodule formation by alizarin red staining, and marker RNA (mRNA) expression by reverse-transcriptase polymerase chain reaction (RT-PCR). Expression of chemokines, such as interleukin-6 (IL-6), IL-8, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), and MIP-3α, were evaluated by RT-PCR. RESULTS: ALP activity, the mineralization, and mRNA expression for odontoblastic markers were enhanced by FGF-2 in HDPCs. FGF-2 also up-regulated the expression of IL-6, IL-8, MCP-1, MIP-1α, and MIP-3α mRNAs, which were attenuated by inhibitors of p38, ERK1/2 and p38 MAP kinases, protein kinase C, phosphoinositide-3 kinase, and NF-κB. CONCLUSION: Taken together, these data suggest that FGF-2 plays a role not only as a differentiation inducing factor in the injury repair processes of pulpal tissue but also as a positive regulator of chemokine expression, which may help in tissue engineering and pulp regeneration using HDPCs. However, the fate of odontoblastic or osteoblastic differentiation, effective local delivery for FGF-2, interaction of chemotatic and odontogenic factors, and other limitations will need to be overcome before a major modality for the treatment of pulp disease. PMID: 20951295 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Effects of morphogen and scaffold porogen on the differentiation of dental pulp stem cells. J Endod. 2010 Nov;36(11):1805-11 Authors: Demarco FF, Casagrande L, Zhang Z, Dong Z, Tarquinio SB, Zeitlin BD, Shi S, Smith AJ, Nör JE INTRODUCTION: Dental pulp tissue engineering is an emerging field that can potentially have a major impact on oral health. However, the source of morphogens required for stem cell differentiation into odontoblasts and the scaffold characteristics that are more conducive to odontoblastic differentiation are still unclear. This study investigated the effect of dentin and scaffold porogen on the differentiation of human dental pulp stem cells (DPSCs) into odontoblasts. METHODS: Poly-L-lactic acid (PLLA) scaffolds were prepared in pulp chambers of extracted human third molars using salt crystals or gelatin spheres as porogen. DPSCs seeded in tooth slice/scaffolds or control scaffolds (without tooth slice) were either cultured in vitro or implanted subcutaneously in immunodefficient mice. RESULTS: DPSCs seeded in tooth slice/scaffolds but not in control scaffolds expressed putative odontoblastic markers (DMP-1, DSPP, and MEPE) in vitro and in vivo. DPSCs seeded in tooth/slice scaffolds presented lower proliferation rates than in control scaffolds between 7 and 21 days (p < 0.05). DPSCs seeded in tooth slice/scaffolds and transplanted into mice generated a tissue with morphological characteristics similar to those of human dental pulps. Scaffolds generated with gelatin or salt porogen resulted in similar DPSC proliferation. The porogen type had a relatively modest impact on the expression of the markers of odontoblastic differentiation. CONCLUSIONS: Collectively, this work shows that dentin-related morphogens are important for the differentiation of DPSC into odontoblasts and for the engineering of dental pulp-like tissues and suggest that environmental cues influence DPSC behavior and differentiation potential. PMID: 20951292 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | The isolation of cell derived extracellular matrix constructs using sacrificial open-cell foams. Biomaterials. 2010 Oct 13; Authors: Wolchok JC, Tresco PA Extracellular matrix derived from human and animal tissues is being used to repair and reconstruct a variety of tissues clinically. The utility of such constructs is limited by the geometry, composition and constitutive properties of the tissue or organ from which the ECM is harvested. To address this limitation, we have developed an approach to isolate extracellular matrix in bulk from populations of living cells grown in culture on three-dimensional substrates. Human biopsy derived fibroblasts were seeded within open-cell foams and cultured in-vitro for periods up to three weeks, after which the synthetic component was removed by incubation in a water miscible solvent. After several wash steps and lyophilization, a white, lacy, multi-molecular construct was isolated. Tandem mass spectroscopy showed that it contained 22 extracellular matrix constituents, including such proteins and proteoglycans as collagen type I and type III, fibronectin, transforming growth factor beta, decorin and biglycan among others. On average 47 mg of construct was isolated for each gram of synthetic substrate initially seeded with cells. The biomaterial harvested from human tracheal fibroblasts had an elastic modulus (250 kPa) and a composition similar to that of human vocal fold tissue, and supported reseeding with human tracheal derived fibroblasts. An important finding was that the approach was useful in isolating ECM from a variety of cell lineages and developmental stages including skin fibroblasts, brain derived astrocytes and mesenchymal stem cells. The results, together with the archival literature, suggest that the approach can be used to produce a range of cell derived constructs with unique physical and chemical attributes for a variety of research and medical applications. PMID: 20950855 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Incorporation of proteinase inhibitors into silk-based delivery devices for enhanced control of degradation and drug release. Biomaterials. 2010 Oct 13; Authors: Pritchard EM, Valentin T, Boison D, Kaplan DL Controlling the rate of silk degradation is critical to its potential use in biomedical applications, including drug delivery and tissue engineering. The effect of protease concentration on accelerating degradation, and the use of ethylenediamine tetraacetic acid (EDTA) on reducing rates of degradation and on drug release from silk-based drug carriers was studied. Increased rates of proteolysis resulted in increased dye release from silk carriers, while EDTA release from the silk carriers inhibited proteolysis. The sustained release of EDTA from silk carriers in combination with the release of the small molecule anti-convulsant adenosine was investigated in vitro. This combination of factors resulted in delayed release of adenosine by inhibiting proteolytic activity. These results introduce a promising strategy to control drug delivery through the regulation of silk degradation rate, achieved via manipulation of local proteolytic activity. This ability to modulate enzyme function could be applicable to a range of silk biomaterial formats as well as other biodegradable polymers where enzymatic functions control biomaterial degradation and drug release rates. PMID: 20950854 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Biocompatibility of adhesive complex coacervates modeled after the sandcastle glue of Phragmatopoma californica for craniofacial reconstruction. Biomaterials. 2010 Oct 13; Authors: Winslow BD, Shao H, Stewart RJ, Tresco PA Craniofacial reconstruction would benefit from a degradable adhesive capable of holding bone fragments in three-dimensional alignment and gradually being replaced by new bone without loss of alignment or volume changes. Modeled after a natural adhesive secreted by the sandcastle worm, we studied the biocompatibility of adhesive complex coacervates in vitro and in vivo with two different rat calvarial models. We found that the adhesive was non-cytotoxic and supported the attachment, spreading, and migration of a commonly used osteoblastic cell line over the course of several days. In animal studies we found that the adhesive was capable of maintaining three-dimensional bone alignment in freely moving rats over a 12 week indwelling period. Histological evidence indicated that the adhesive was gradually resorbed and replaced by new bone that became lamellar across the defect without loss of alignment, changes in volume, or changes in the adjacent uninjured bone. The presence of inflammatory cells was consistent with what has been reported with other craniofacial fixation methods including metal plates, screws, tacks, calcium phosphate cements and cyanoacrylate adhesives. Collectively, the results suggest that the new bioadhesive formulation is degradable, osteoconductive and appears suitable for use in the reconstruction of craniofacial fractures. PMID: 20950851 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Production and characterization of engineered alginate-based microparticles containing ECM powder for cell/tissue engineering applications. Acta Biomater. 2010 Oct 12; Authors: Mazzitelli S, Luca G, Mancuso F, Calvitti M, Calafiore R, Nastruzzi C, Johnson S, Badylak SF A method for the production of engineered alginate-based microparticles, containing extracellular matrix and neonatal porcine Sertoli cells (SC) is described. As a source for extracellular matrix, a powder form of isolated and purified urinary bladder matrix (Urinary Bladder Matrix, UBM), was employed. We demonstrated that the incorporation of UBM does not significantly alter the morphological and dimensional characteristics of the microparticles. The alginate microparticles were used for Sertoli cell encapsulation as an immunoprotective barrier for transplant purposes, while the co-entrapped UBM promoted retention of cell viability and function. These engineered microparticles might represent a novel approach to enhance immunological acceptance and implement the functional life-span of the entrapped cells, for cell/tissue engineering applications. In this respect it is noteworthy that isolated neonatal porcine SC, administered alone in highly biocompatible microparticles, led to diabetes prevention and reversion in nonobese diabetic (NOD) mice. PMID: 20950716 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Overexpression of ΔNp63α induces a stem cell phenotype in MCF7 breast carcinoma cell line through the Notch pathway. Cancer Sci. 2010 Nov;101(11):2417-24 Authors: Du Z, Li J, Wang L, Bian C, Wang Q, Liao L, Dou X, Bian X, Zhao RC To elucidate a role of ΔNp63α in breast cancer, the expression levels of p63, estrogen receptor, progesterone receptor, p53, CK5, cerBb-2, and Notch1 were assayed in 50 clinical breast cancer specimens using immunochemistry. P63 was highly expressed in a subset of breast cancer with basal-like features. We then transfected MCF7 cells with ΔNp63α plasmid, and assayed its cancer stem cell-like features after transfection. Overexpression of ΔNp63α in MCF7 cells increased the percentage of CD24(-) CD44(+) subpopulation from 2.2 ± 0.2% to 25.1 ± 1.5% (P < 0.05) and led to increased cancer cell proliferation, clonogenicity, anchorage-independent growth, and the incidence of xenograft grown in vivo. In addition, ΔNp63α overexpressing cancer cells were more drug resistant. Further studies suggested ΔNp63α-induced activation of the Notch pathway may play a role in these effects. Chromatin immunoprecipitation confirmed that ΔNp63α could directly bind to Notch1. In clinical breast cancer specimens, the expression level of p63 was also found to positively correlate with the expression level of Notch1. Our results suggest that ΔNp63α might serve as a tumor initiating transcription factor in breast cancer. (Cancer Sci 2010; 101: 2417-2424). PMID: 20950370 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Peripheral nerve regeneration in the MRL/MpJ ear wound model. J Anat. 2010 Oct 18; Authors: Buckley G, Metcalfe AD, Ferguson MW The MRL/MpJ mouse displays an accelerated ability to heal ear punch wounds without scar formation (whereas wounds on the dorsal surface of the trunk heal with scar formation), offering a rare opportunity for studying tissue regeneration in adult mammals. A blastema-like structure develops and subsequently the structure of the wounded ear is restored, including cartilage, skin, hair follicles and adipose tissue. We sought to assess if the MRL/MpJ strain also possessed an enhanced capacity for peripheral nerve regeneration. Female MRL/MpJ and C57BL/6 mice were wounded with a 2-mm excisional biopsy punch to the centre of each ear and two 4-mm excisional biopsy punches to the dorsal skin. Immunohistochemical dual staining of pan-neurofilament and CD31 markers was used to investigate reinnervation and vascularisation of both the dorsal surface of the trunk and ear wounds. The MRL/MpJ mouse ear exhibited a significantly (P > 0.01) higher density of regenerated nerves than C57BL/6 between 10 and 21 days post-wounding when the blastema-like structure was forming. Unlike dorsal skin wounds, nerve regeneration in the ear wound preceded vascularisation, recapitulating early mammalian development. Immunohistochemical data suggest that factors within the blastemal mesenchyme, such as aggrecan, may direct nerve regrowth in the regenerating ear tissue. PMID: 20950365 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
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