Organization Of Connective Tissue Research Articles

Concise Review: Stem Cells in the Corneal Stroma

The cornea is a tough transparent tissue admitting and focusing light in the eye. More than 90% of the cornea is stroma, a highly organized, transparent connective tissue maintained by keratocytes, quiescent mesenchymal cells of neural crest origin. A small population of cells in the mammalian stroma displays properties of mesenchymal stem cells, including clonal growth, multipotent differentiation, and expression of an array of stem cell-specific markers. Unlike keratocytes, the corneal stromal stem cells (CSSCs) undergo extensive expansion in vitro without loss of the ability to adopt a keratocyte phenotype. Several lines of evidence suggest CSSCs to be of neural crest lineage and not from bone marrow. CSSCs are localized in the anterior peripheral (limbal) stroma near to stem cells of the corneal epithelium. CSSCs may function to support potency of the epithelial stem cells in their unique limbal niche. On the other hand, little information is available documenting a role for CSSCs in vivo in stromal wound healing or regeneration. In vitro CSSCs reproduce the highly organized connective tissue of the stroma, demonstrating a potential use of these cells in tissue bioengineering. Direct introduction of CSSCs into the corneal stroma generated transparent tissue in a mouse model of corneal opacity. Human CSSCs injected into mice corneas did not elicit immune rejection over an extended period of time. The CSSCs therefore appear offer an opportunity to develop cell- and tissue-based therapies for irreversible corneal blindness, conditions affecting more than 10 million individuals worldwide.

The engineering of organized human corneal tissue through the spatial guidance of corneal stromal stem cells

Corneal stroma is an avascular connective tissue characterized by layers of highly organized parallel collagen fibrils, mono-disperse in diameter with uniform local interfibrillar spacing. Reproducing this level of structure on a nano- and micro-scale may be essential to engineer corneal tissue with strength and transparency similar to that of native cornea. A substrate of aligned poly(ester urethane) urea (PEUU) fibers, 165 ± 55 nm in diameter, induced alignment of cultured human corneal stromal stem cells (hCSSCs) which elaborated a dense collagenous matrix, 8–10 μm in thickness, deposited on the PEUU substratum. This matrix contained collagen fibrils with uniform diameter and regular interfibrillar spacing, exhibiting global parallel alignment similar to that of native stroma. The cells expressed high levels of gene products unique to keratocytes. hCSSCs cultured on PEUU fibers of random orientation or on a cast film of PEUU also differentiated to keratocytes and produced abundant matrix, but lacked matrix organization. These results demonstrate the importance of topographic cues in instructing organization of the transparent connective tissue of the corneal stroma by differentiated keratocytes. This important information will help with design of biomaterials for a bottom-up strategy to bioengineer spatially complex, collagen-based nano-structured constructs for corneal repair and regeneration.

The thrombospondins.

Thrombospondins are evolutionarily conserved, calcium-binding glycoproteins that undergo transient or longer-term interactions with other extracellular matrix components. They share properties with other matrix molecules, cytokines, adaptor proteins, and chaperones, modulate the organization of collagen fibrils, and bind and localize an array of growth factors or proteases. At cell surfaces, interactions with an array of receptors activate cell-dependent signaling and phenotypic outcomes. Through these dynamic, pleiotropic, and context-dependent pathways, mammalian thrombospondins contribute to wound healing and angiogenesis, vessel wall biology, connective tissue organization, and synaptogenesis. We overview the domain organization and structure of thrombospondins, key features of their evolution, and their cell biology. We discuss their roles in vivo, associations with human disease, and ongoing translational applications. In many respects, we are only beginning to appreciate the important roles of these proteins in physiology and pathology.

Influence of low-level laser therapy on wound healing in nicotine-treated animals

Low-level laser therapy (LLLT) has been shown to have several biological effects that favor the healing process, and nicotine has been shown to delay the healing process. In this study we investigated the healing of open wounds created on the back of rats treated with nicotine with or without LLLT. Of 115 animals, 59 received subcutaneous injections of saline solution, and the others received subcutaneous injections of nicotine (3 mg/kg body weight), twice a day throughout the study period. After 30 days, skin wounds were created on the back of the animals. The animals receiving saline injections were divided into two groups: group 1 (G1, n = 29), in which the wounds were left untreated, and group 2 (G2, n = 30), in which the wounds were treated with LLLT (GaAlAs, 660 nm, 30 mW, 5.57 J/cm(2) per point, 0.39 J, 13 s per point, 0.42 W/cm(2)). The animals receiving nicotine injections were also divided into two groups: group 3 (G3, n = 29), in which the wounds were left untreated, and group 4 (G4, n = 27), in which the wounds were treated with LLLT. The animals were killed 3, 7 or 14 days after surgery. Wound healing was evaluated histologically both qualitatively and semiquantitatively. Wounds of G2 showed a delay in epithelial migration and connective tissue organization compared to those of G1. Wounds of G2 showed faster healing than those of G1; similarly, wounds of G4 showed more advanced healing than those of G3. LLLT acted as a biostimulatory coadjuvant agent balancing the undesirable effects of nicotine on wound tissue healing.

Dynamic Interactions between the Myocyte and Extracellular Matrix Promote Myocyte Differentiation and Myofibril Assembly

During development, skeletal myoblasts differentiate into myocytes and skeletal myotubes with mature contractile structures that are precisely oriented with respect to surrounding cells and tissues. Establishment of this highly ordered structure requires reciprocal interactions between the differentiating myocytes and the surrounding extracellular matrix to form correctly positioned and well organized connective tissue attachments from the skeletal muscle to the bony skeleton. Using the developing zebrafish embryo as a model, we examined the relationship between new myofibril assembly and the organization of the membrane domains involved in cell-extracellular matrix interactions. We determined that apical clustering of integrins was associated with changes in cell morphology which included myoblast elongation along the body axis. Through the analysis of zebrafish embryos depleted of obscurin A that have impaired formation of the myotendinous junctions, we determined that cell elongation and, as a result, new myofibril formation was delayed in regions that lacked integrin clustering and fibronectin matrix organization. In addition, it was noted that striated myofibrils first form at the cell periphery and are associated with the early patterning of the lateral sarcolemma. These specialized membrane domains will ultimately form mature lateral connections between the myofibril and the extracellular matrix at the costameres. We have also determined that the giant cytoskeletal and sarcomeric protein obscurin has an important role in the organization and maturation of the MTJ and in the maturation of the costamere. As myocyte-extracellular matrix connections have critical roles in force transduction and tension-mediated signaling defining the processes that promote and sustain these connections will have important implications for the understanding the pathogenesis of, and developing new treatment strategies for, a range of myopathies and muscular dystrophies.

Distribution of factor XIIIa containing cells and collage nous components in radicular cysts: Histochemical and immunohistochemical study

Objective: 1) To differentiate various connective tissue layers in radicular cysts 2) To find the correlation between FXIIIa containing cells and fibrosis. Factor XIII, fibrin stabilizing factor, stabilizes the clot for blood coagulation and is also responsible for connective tissue organization in healing and tissue repair. FXIIIa has an important role during the process of fibrosis in various lesions, so we conducted a study to find its role in radicular cyst. Study Design: 10 cases of radicular cyst, reported in our hospital were selected. Clinical and follow up data of those cases were collected from the archives. Material and Methods: Histochemical analysis with Masson’s trichrome was done to differentiate the three layers of radicular cyst. Immunocytochemical staining for distribution of factor XIIIa was carried out. Stained slides were examined under high power. After counting cell, data was analysed statistically. Results: Positive reaction for Factor XIIIa was observed in certain connective tissue cells in all the layers of radicular cysts. FXIIIa containing cells were numerous in intermediate layer as compared to outer fibrous layer. FXIIIa containing cells and fibrosis was increased in case of radiographically well circumscribed lesion than the diffuse lesion. It can be concluded that factor XIIIa containing cells and collagenous components in radicular cyst play an important role in fibrosis and is also correlated with healing of the lesion.

In Vivo Confocal Microscopy of Trachoma in Relation to Normal Tarsal Conjunctiva

ObjectiveTo describe the in vivo confocal microscopy (IVCM) appearances of the tarsal conjunctiva in trachoma compared with the appearance of healthy conjunctiva and to develop grading systems for IVCM examination of the tarsal conjunctiva for use in future studies on trachoma and other conjunctival diseases.DesignProspective observational study.ParticipantsIn vivo confocal microscopy examination was performed on 302 clinically normal adults, 16 clinically normal children, 750 adults with trachomatous conjunctival scarring, and 25 children with active trachoma.MethodsClinical evaluation was performed with ×2.5 loupes, and IVCM examination of the upper tarsal conjunctiva was carried out with a Heidelberg Retina Tomograph 3 with the Rostock Cornea Module (Heidelberg Engineering GmbH, Dossenheim, Germany).Main Outcome MeasuresIn vivo confocal microscopy images were analyzed for cellular and tissue changes associated with trachomatous inflammation and scarring compared with healthy subjects.ResultsTrachomatous subjects with follicular and papillary inflammation had an increased inflammatory cellular infiltrate, including dendritiform cells, discrete follicular and papillary structures, and cystic lacunae suggestive of tissue edema. Trachomatous conjunctival scarring was seen with IVCM as organization of the subepithelial connective tissue into bands/sheets. Grading systems for inflammatory changes and scarring were developed, with the system for scarring showing good interobserver agreement with an intraclass coefficient of 0.88.ConclusionsIn vivo confocal microscopy provides a powerful tool for examining the ocular surface. Numerous cellular and tissue changes were observed in subjects with trachoma, the first time IVCM has been applied to this disease. These changes both complement and add to previous histologic analyses. In vivo confocal microscopy promises to provide new insights into the pathogenesis of trachoma and other conjunctival diseases.Financial Disclosure(s)The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Tissue response to a new type of biomaterial implanted subcutaneously in rats

A new type of resorbable biomaterial intended for pelvic reconstruction was tested with respect to tissue regeneration and biocompatibility in rats. The biomaterial consisted of methoxypolyethyleneglycol-poly(lactic-co-glycolic acid) (MPEG-PLGA). Implants were pure, enriched with extra-cellular matrix (ECM) or estrogen. Ten implants of each type were tested for 3 and 8weeks, respectively. Histological assessment of connective tissue organization, inflammation, vascularization, and thickness of regenerated tissue was undertaken. All implants had a high degree of biocompatibility. ECM-enriched implants had significantly higher inflammatory scores compared to pure implants at 3weeks. At 8weeks, neither of the parameters differed significantly. No trace of the implants remained. The MPEG-PLGA is highly biocompatible, degrades quickly, and seems inert in the process of tissue regeneration. Thus, it is hardly a candidate per se in reinforcement of pelvic reconstruction, but it could have a future role as carrier for stem cells.

COL1A1 oligodeoxynucleotides decoy: Biochemical and morphologic effects in an acute wound repair model

Type I collagen is an integral component of granulation tissue and scar, that is highly dependent on TGFβ1, a member of a pro-fibrotic family of cytokines, for its promotion and deposition. Blocking COL1A1 gene transcription obstructs type I collagen synthesis, hindering the progress of granulation tissue deposition and fibrosis. Local injections of a double stranded oligodeoxynucleotide (dsODN) decoy, containing the TGFβ1 regulatory element that is located in the distal promoter of the COL1A1 gene, were investigated in a rat polyvinyl alcohol (PVA) sponge granulation tissue implant model. The effects on the granulation tissue deposition by dsODN decoy therapy were evaluated by the synthesis of types I and III collagens as well as ED-A (cellular) fibronectin. Fluorescently labeled dsODN was used to identify the distribution of the decoy molecules in the sponge implant relative to the observed histological effects. Morphological alterations in cells and changes in the organization of connective tissue were documented and evaluated. Collagen levels were reduced by half in implants treated with 10 nM dsODN decoy compared to scrambled dsODN-treated implants. Histologically, dsODN decoy treated implants had an increased cellular density without a corresponding increase in deposited connective tissue. Polarized light birefringence pattern of Sirius red-stained sections showed less collagen fibers accumulating between fibroblasts. The highest concentration of fluorescently labeled dsODN was identified within the interior margin of sponge implants, correlating to increased cellular density and an altered birefringence patterns. In conclusion, 10 nM dsODN decoy therapy reduced collagen deposition and altered the organization of granulation tissue, supporting its potential as a localized anti-fibrotic therapy for limiting fibrotic conditions.

Initial endosseous healing response to lactide/ glycolide copolymer

Introduction: The search for less invasive treatments, with fast and effective bone regeneration, has lead to the development of synthetic bioresorbable alternatives for bone graft. The commercial product FisiograftTM gel (Ghimas Spa, Italy), based on lactide-glycolide copolymer, is used as an injectable biocompatible and bioresorbable material for filling bone defects in dental surgery applications. These polymers are also used in the production of suture threads, pins and plates for bone fixation, and barriers for guided tissue regeneration. Objective: The main objective of this pilot study was to observe the initial bone healing response after the application of polylactide-glycolide graft material in adult animals. Material and methods: Bone defects were prepared in right and left femora of 12 month-old male Wistar rats. The defects in one leg received the synthetic graft material and the contra-lateral defects did not receive any treatment. After four days, the animals were subjected to euthanasia, the femora were removed, and tissue blocks were prepared for histological analysis. Results: Blood clot remained in the centre of control defects with initial connective tissue organization on the edges. The graft material was observed in the centre of the treated defects, restricted to the area where it was applied, with neovascularization next to the graft material. The pattern of bone healing did not differ between groups, starting from the margins of the defects and from bone fragments, with neovascularization followed by deposition of non-mineralized bone matrix towards the centre. Conclusion: The results indicate that the lactide-glycolide copolymer gel was effective as a filling and osteoconductive material, allowing tissue healing during its resorption process. Additional studies are necessary to verify its capacity to promote bone regeneration.

The contribution of Roberto Montesano to the study of interactions between epithelial sheets and the surrounding extracellular matrix

The interactions between epithelial cells and the surrounding extracellular matrix are a central issue in morphogenesis studies. Roberto Montesano and colleagues at the University Medical Center of Geneva, Switzerland, have extensively investigated the mechanisms underlying two morphogenetic processes: the formation of new capillary blood vessels from pre-existing ones (angiogenesis) and the generation of branching epithelial tubules (tubulogenesis), which are crucial events in the development of most parenchymal organs. Dr. Montesano has contributed to clarifying some cellular and molecular mechanisms of angiogenesis and tubulogenesis using an original three-dimensional cell culture system which replicates key events of angiogenesis and tubulogenesis, thereby facilitating molecular analysis. A major advance of this technique over conventional monolayer cultures is that cells can be embedded within a lattice of reconstituted collagen fibrils which mimics the three-dimensional organization of connective tissue matrices.The results of these studies support the notion that cell interactions with the surrounding extracellular matrix are crucial determinants of cell responses to growth factors and that epithelial tissues morphogenesis is governed by the interplay of two different classes of signaling molecules, i.e. paracrine-acting growth factors and insoluble extracellular matrix components.

Early healing of implants placed into fresh extraction sockets: an experimental study in the beagle dog. III:soft tissue findings

To describe histologically the early phases of soft tissue healing to implants placed into fresh extraction sockets. In 16 beagle dogs, 64 3.25-mm-wide cylindrical screw implants were inserted into the distal sockets of the third and fourth lower premolars using a one-stage trans-mucosal healing protocol. Biopsies were then taken at 1, 2, 4 and 8 weeks and prepared for histological examination. One-week specimens showed a junctional epithelium and an underlying loose connective tissue rich in inflammatory cells. At 2 weeks, signs of epithelial proliferation and a more organized connective tissue were observed. At 4 and 8 weeks, inflammation was absent; the epithelium appeared mature and in close contact with the surface of the healing abutment or the implant. The connective tissue was dense in an area close to the implant surface and the fibres were aligned parallel to the implant surface. The soft tissue dimensions at 8 weeks were approximately 5 mm, including about 3-3.5 mm of epithelium and 1-1.5 mm of connective tissue. Soft tissue healing to implants placed in fresh extraction sockets may result in a longer epithelial interface than implants placed in a healed ridge.

Integrin α1β1 is involved in the differentiation into myofibroblasts in adult reactive tissues in vivo

Connective tissue cell activation is of importance during reactive conditions such as solid tumour growth, wound healing and pannus formation in rheumatoid arthritis. Here, we have compared connective tissue cells of mesenchymal origin in human tissues from these conditions and their normal counterparts using a panel of cell-type-specific markers. In particular, we investigated variations of integrin expression among connective tissue cell phenotypes. Connective tissue cell populations were defined based on their association with the microvasculature and their expression of activation markers. The phenotype of these cells varied according to the type of pathological connective tissue examined. Our morphological data from human tissues suggested that the α1β1 integrin, a collagen/laminin receptor, is involved in the differentiation of precursor cells into myofibroblasts. To mechanistically investigate this hypothesis, we employed experimental models for carcinoma growth and wound healing utilizing α1 integrin-deficient mice. The data confirmed that the α1β1 integrin is of importance not only for the differentiation of mesenchymal cells into myofibroblasts but also for the neovascularization and connective tissue organization and emphasize the importance of myofibroblasts in the pathophysiology of tissue repair, inflammation and tumour growth.

Evaluation of the Tissue Reaction to Fast Endodontic Cement (CER) and Angelus MTA

IntroductionA new cement (CER; Cimento Endodôntico Rápido or fast endodontic cement) has been developed to improve handling properties. It is a formulation that has Portland cement in gel. However, there had not yet been any study evaluating its biologic properties. The purpose of this study was to evaluate the rat subcutaneous tissue response to CER and Angelus MTA. MethodsThe materials were placed in polyethylene tubes and implanted into dorsal connective tissue of Wistar rats for 7, 30, and 60 days. The specimens were prepared to be stained with hematoxylin-eosin or von Kossa or not stained for polarized light. The presence of inflammation, predominant cell type, calcification, and thickness of fibrous connective tissue were recorded. Scores were defined as follows: 0, none or few inflammatory cells, no reaction; 1, <25 cells, mild reaction; 2, 25–125 cells, moderate reaction; 3, >125 cells, severe reaction. Fibrous capsule was categorized as thin when thickness was <150 μm and thick at >150 μm. Necrosis and formation of calcification were both recorded. ResultsBoth materials Angelus MTA and CER caused moderate reactions at 7 days, which decreased with time. The response was similar to the control at 30 and 60 days with Angelus MTA and CER, characterized by organized connective tissue and presence of some chronic inflammatory cells. Mineralization and granulations birefringent to polarized light were observed with both materials. ConclusionsIt was possible to conclude that CER was biocompatible and stimulated mineralization.

Effects of basic fibroblast growth factor‐2 and hyaluronic acid on tracheal wound healing

To evaluate basic fibroblast growth factor-2 (BFGF) and hyaluronic acid (HA) effects on a surgically produced tracheal defect. Animal model. Anterior punch lesions were created on 33 male rabbits divided into three equal groups. Group 1 (Control) received a normal saline (NS)-soaked collagen sponge directly on the defect, group 2 (HA alone) a NS-soaked HA sponge, and group 3 (BFGF+HA) a 10 ng/mL BFGF-soaked HA sponge. Sponge fixation and surgical closure were followed by a 90-day healing period, then animal sacrifice. Harvested tracheas were fixed, imbedded, sectioned, and stained with hematoxylin and eosin or safranin-O. Histopathological measures included: chondrocyte death, chondrocyte proliferation (both reported as number of rabbits displaying death or proliferation per group/total rabbits per group [%]), connective tissue (CT) organization (graded on a scale), epithelial closure (1-3 scale), and inflammation (1-4 scale). The final three measures are reported as an average grade per group, where values closer to 1 signify improved healing, whereas higher values signify poorer healing. Chondrocyte death: Control, 8/11 (72.7%); HA alone, 5/11 (45.5%); BFGF+HA 5/11 (45.5%). Chondrocyte proliferation: 3/11 (27.3%), 7/11 (63.6%), and 9/11 (81.8%), respectively. CT organization: 2.00, 1.82, 1.64. Epithelial closure: 1.18, 1.09, and 1.00. Inflammation: 2.82, 1.82, and 1.73. Statistical comparisons: significantly improved chondrocyte proliferation for BFGF+HA (P = .015) and reduced inflammation for HA alone (P = .011) and BFGF+HA (P = .004) compared to controls. BFGF+HA applied to an anterior tracheal defect significantly improves chondrocyte proliferation; HA alone and BFGF+HA significantly reduce inflammation. BFGF+HA and HA alone may improve tracheal wound healing.

Macrophage Phenotype as a Determinant of Biologic Scaffold Remodeling

Macrophage phenotype can be characterized as proinflammatory (M1) or immunomodulatory and tissue remodeling (M2). The present study used a rat model to determine the macrophage phenotype at the site of implantation of two biologic scaffolds that were derived from porcine small intestinal submucosa (SIS) and that differed mainly according to their method of processing: the Restore device (SIS) and the CuffPatch device (carbodiimide crosslinked form of porcine-derived SIS (CDI-SIS)). An autologous tissue graft was used as a control implant. Immunohistologic methods were used to identify macrophage surface markers CD68 (pan macrophages), CD80 and CCR7 (M1 profile), and CD163 (M2 profile) during the remodeling process. All graft sites were characterized by the dense population of CD68+ mononuclear cells present during the first 4 weeks. The SIS device elicited a predominantly CD163+ response (M2 profile, p < 0.001) and showed constructive remodeling at 16 weeks. The CDI-SIS device showed a predominately CD80+ and CCR7+ response (M1 profile, p < 0.03), and at 16 weeks was characterized by chronic inflammation. The autologous tissue graft showed a predominately CD163+ response (M2) at 1 week, with a dual M1/M2 population (CD80+, CCR7+, and CD163+) by 2 and 4 weeks and moderately well organized connective tissue by 16 weeks. The processing methods used during the manufacturing of a biologic scaffold can have a profound influence upon the macrophage phenotype profile and downstream remodeling events. Routine histologic examination alone is inadequate to determine the phenotype of mononuclear cells that participate in the host response to the scaffold.

Biocompatibility of Bovine Anorganic Xenograft

Porous granules without organic residues were produced from bovine medular anorganic bone. Sample showed carbonate content and crystalline order similar to natural bone. The cytotoxicity of anorganic bovine xenograft (Ossĕus®) was valuated from fibroblasts (1.5x104/cm2) cultured in serial diluted extract (0 – 100%) of Ossĕus plus 10% of fetal bovine serum (FBS). Pure extract (100%) reduced in 15% the number of viable cells (p&lt;0.05, ANOVA, Tukey test) indicating very low cytotoxicity. Samples were implanted in the subcutaneous tissue of mice in order to evaluate tissue reaction. An organized connective tissue in contact to the granules was observed nine weeks after implantation. The anorganic bovine xenograft (Ossĕus®) was biocompatible and its behavior and osteoconduction potential should be evaluated in bony defects.

A review of ageing and an examination of clinical methods in the assessment of ageing skin. Part 2: Clinical perspectives and clinical methods in the evaluation of ageing skin

With the advancement of skin research, today's consumer has increased access to technological information about ageing skin and hair care products. As a result, there is a rapidly increasing demand for proof of efficacy of these products. Recognizing these demands has led to the development and validation of many clinical methods to measure and quantify ageing skin and the effects of anti-ageing treatments. Many of the current testing methods used to research and evaluate anti-ageing product claim to employ sophisticated instruments alongside more traditional clinical methods. Intelligent use of combined clinical methods has enabled the development of technologically advanced consumer products providing enhanced efficacy and performance. Of non-invasive methods for the assessment and quantification of ageing skin, there is a plethora of tools available to the clinical researcher as defined by key clinically observed ageing parameters: skin roughness and surface texture; fine lines and wrinkles; skin pigmentation; skin colour; firmness and elasticity; hair loss; and proliferative lesions. Furthermore, many clinical procedures for the evaluation of ageing skin treatments are combined with invasive procedures, which enable added-value to claims (such as identification and alteration of biochemical markers), particularly in those cases where perception of product effect needs additional support. As discussed herein, clinical methods used in the assessment of skin ageing are many and require a disciplined approach to their use in such investigations.

Long-term results with Matrix coils vs. GDC: an angiographic and histopathological comparison

The aim of the study was to compare standard platinum Guglielmi detachable coils (GDC) with coated platinum coils (Matrix; both Boston Scientific, Fremont, CA) regarding handling, complications, occlusion and recanalization rate after 3 and 6A months. Aneurysms in the right common carotid artery were created in 25 rabbits. The animals were divided into five groups of five animals each. The animals of group 1 (the control group) received no treatment of the induced aneurysms, the animals of groups 2 and 3 (killed at 3 and 6A months) were treated with standard GDC, and the animals of groups 4 and 5 (killed at 3 and 6A months) were treated with Matrix coils. Histopathological evaluation showed organized thrombus formation and connective tissue with neovascularization around the implanted coils in all the treated groups. The achieved occlusion rates in groups 2 and 3 were identical to those in groups 4 and 5. Thus the long-term results of aneurysm treatment with GDC and Matrix coils show no differences regarding occlusion and recanalization rates. The only noticeable difference was the difference in handling. More force was required to pushing the Matrix coils forward through the microcatheter and there was more friction in coil interaction in the aneurysm. The bioactive coating of the Matrix coil produces no significant benefit in achieving higher occlusion and lower recanalization rates, and the coil is more difficult to handle. Future bioactive coils must be shown to produce significantly better long-term results than GDC and their ease of handling has to be improved.

In vivo biocompatibility of ultra-short single-walled carbon nanotube/biodegradable polymer nanocomposites for bone tissue engineering

Scaffolds play a pivotal role in the tissue engineering paradigm by providing temporary structural support, guiding cells to grow, assisting the transport of essential nutrients and waste products, and facilitating the formation of functional tissues and organs. Single-walled carbon nanotubes (SWNTs), especially ultra-short SWNTs (US-tubes), have proven useful for reinforcing synthetic polymeric scaffold materials. In this article, we report on the in vivo biocompatibility of US-tube reinforced porous biodegradable scaffolds in a rabbit model. US-tube nanocomposite scaffolds and control polymer scaffolds were implanted in rabbit femoral condyles and in subcutaneous pockets. The hard and soft tissue response was analyzed with micro-computed tomography (micro CT), histology, and histomorphometry at 4 and 12 weeks after implantation. The porous US-tube nanocomposite scaffolds exhibited favorable hard and soft tissue responses at both time points. At 12 weeks, a three-fold greater bone tissue ingrowth was seen in defects containing US-tube nanocomposite scaffolds compared to control polymer scaffolds. Additionally, the 12 week samples showed reduced inflammatory cell density and increased connective tissue organization. No significant quantitative difference in polymer degradation was observed among the various groups; qualitative differences between the two time points were consistent with expected degradation due to the progression of time. Although no conclusions can be drawn from the present study concerning the osteoinductivity of US-tube nanocomposite scaffolds, the results suggest that the presence of US-tubes may render nanocomposite scaffolds bioactive assisting osteogenesis.