SciCombinator

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Concept: Type-I collagen

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Autologous techniques for the reconstruction of pediatric microtia often result in suboptimal aesthetic outcomes and morbidity at the costal cartilage donor site. We therefore sought to combine digital photogrammetry with CAD/CAM techniques to develop collagen type I hydrogel scaffolds and their respective molds that would precisely mimic the normal anatomy of the patient-specific external ear as well as recapitulate the complex biomechanical properties of native auricular elastic cartilage while avoiding the morbidity of traditional autologous reconstructions.

Concepts: Collagen, Extracellular matrix, Skeletal system, Tissues, Ear, Reconstruction era of the United States, Reconstruction, Type-I collagen

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The Achilles tendon has a high incidence of rupture, and the healing process leads to a disorganized extracellular matrix (ECM) with a high rate of injury recurrence. To evaluate the effects of different conditions of low-level laser (LLL) application on partially tenotomized tendons, adult male rats were divided into the following groups: G1, intact; G2, injured; G3, injured + LLL therapy (LLLT; 4 J/cm(2) continuous); G4, injured + LLLT (4 J/cm(2), 20 Hz); G5, injured; G6, injured + LLLT (4 J/cm(2) continuous); and G7, injured + LLLT (4 J/cm(2), 20 Hz until the 7th day and 2 kHz from 8 to 14 days). G2, G3, and G4 were euthanized 8 days after injury, and G5, G6, and G7 were euthanized on the 15th day. The quantification of hydroxyproline (HOPro) and non-collagenous protein (NCP), zymography for matrix metalloproteinase (MMP)-2 and MMP-9, and Western blotting (WB) for collagen types I and III were performed. HOPro levels showed a significant decrease in all groups (except G7) when compared with G1. The NCP level increased in all transected groups. WB for collagen type I showed an increase in G4 and G7. For collagen type III, G4 presented a higher value than G2. Zymography for MMP-2 indicated high values in G4 and G7. MMP-9 increased in both treatment groups euthanized at 8 days, especially in G4. Our results indicate that the pulsed LLLT improved the remodeling of the ECM during the healing process in tendons through activation of MMP-2 and stimulation of collagen synthesis.

Concepts: Collagen, Extracellular matrix, Cartilage, Matrix metalloproteinase, Tendon, Achilles tendon, Tendons, Type-I collagen

28

Bone morphogenetic proteins (BMPs) are the most potent osteoinductive growth factors. However, a delivery system is essential to take advantage of the osteoinductive effect of BMPs. The purpose of this study was to develop a sustained delivery system for recombinant human bone morphogenetic protein-2 (BMP-2). We covalently attached heparin to a cross-linked collagen type I coated tricalciumphosphate/hydroxyapatite (TCP/HA) bone substitute and subsequently loaded it with BMP-2. To systematically evaluate the contribution of each component with respect to the binding and release of BMP-2, six constructs were prepared and characterized: TCP/HA, TCP/HA with collagen (TCP/HACol), and TCP/HA with collagen and heparin (TCP/HAColHep) with and without BMP-2 (B). More BMP-2 bound to the TCP/HAColHep + B (92.9 ± 4.8 ng BMP-2/mg granule) granules as compared to the TCP/HACol + B (69.0 ± 9.6 ng BMP-2/mg granule) and TCP/HA + B granules (62.9 ± 5.4 ng BMP-2/mg granule). No difference in release pattern was found between the TCP/HA + B and TCP/HACol + B granules. Up to day 14, BMP-2 was still bound to the TCP/HAColHep + B granules, whereas most BMP had been released from TCP/HACol + B and TCP/HA + B granules at that time. After 21 days most BMP-2 also had been released from the TCP/HAColHep + B granules. The local and sustained delivery system for BMP-2 developed in this study may be useful as a carrier for BMP-2 and could possibly enhance bone regeneration efficacy for the treatment of large bone defects.

Concepts: Bone, Collagen, Developmental biology, Bone morphogenetic protein, Release, Type-I collagen, Bone morphogenetic protein 2, BMP-2

26

Systemic sclerosis is an autoimmune condition of unknown aetiology. The disease consists of autoimmunity, vascular disease, inflammation and ultimately fibrosis. It is characterised by accumulation of an excessive amount of extracellular matrix molecules that primarily include collagen type I. IL-6 is a profibrotic cytokine that is elevated in the autoimmune condition systemic sclerosis and is known to induce collagen I expression but the mechanism (s) behind this induction are currently unknown.

Concepts: Immune system, Collagen, Extracellular matrix, Rheumatoid arthritis, Lupus erythematosus, Autoimmune diseases, Autoimmunity, Type-I collagen

24

Study Design Pilot study using the rabbit model. Objective Low back pain is often associated with disk degeneration. Cell therapy for degenerating disks may promote tissue regeneration and repair. Human dermal fibroblasts, obtained from the patient’s skin tissue or donated tissue, may be a promising cell therapy option for degenerating disks. The objective of these studies is to determine the effects of intradiscal transplantation of neonatal human dermal fibroblasts (nHDFs) on intervertebral disk (IVD) degeneration by measuring disk height, magnetic resonance imaging (MRI) signal intensity, gene expression, and collagen immunostaining. Methods New Zealand white rabbits (n = 16) received an annular puncture to induce disk degeneration and were treated with nHDFs or saline 4 weeks later. At 2 and 8 weeks post-treatment, X-ray and MRI images were obtained. IVDs were isolated and examined for changes in collagen staining and gene expression. Results In the nHDF-treated group, there was a 10% increase in the disk height index after 8 weeks of treatment (p ≤ 0.05), and there was no significant difference in the saline-treated group. When compared with the saline-treated disks, disks treated with nHDFs showed reduced expression of inflammatory markers, a higher ratio of collagen type II over collagen type I gene expression, and more intense immunohistochemical staining for both collagen types I and II. Conclusions Human dermal fibroblast introduction into the disk reduced inflammation and promoted tissue rich in both type I and type II collagens. The results of this study suggest that nHDFs would be a feasible cell therapy option for disk degeneration.

Concepts: Gene, Cell, Collagen, Extracellular matrix, Fibroblast, Cellular differentiation, Magnetic resonance imaging, Type-I collagen

2

Non-muscle invasive bladder cancers (NMIBC) are generally curable, while ~15% progresses into muscle-invasive cancer with poor prognosis. While efforts have been made to identify genetic alternations associated with progression, the extracellular matrix (ECM) microenvironment remains largely unexplored. Type I collagen is a major component of the bladder ECM, and can be altered during cancer progression. We set out to explore the association of type I collagen with NMIBC progression.

Concepts: Lung cancer, Collagen, Extracellular matrix, Urology, Urinary bladder, Bladder cancer, Cystitis, Type-I collagen

2

The chronological development and natural history of cerebral aneurysms (CAs) remain incompletely understood. We used (14)C birth dating of a main constituent of CAs, that is, collagen type I, as an indicator for biosynthesis and turnover of collagen in CAs in relation to human cerebral arteries to investigate this further.

Concepts: Amino acid, Atherosclerosis, Collagen, Natural environment, Aneurysm, Cerebral aneurysm, Nature, Type-I collagen

2

The extracellular matrix (ECM) of mammalian tissues has been isolated, decellularized and utilised as a scaffold to facilitate the repair and reconstruction of numerous tissues. Recent studies have suggested that superior function and complex tissue formation occurred when ECM scaffolds were derived from site specific homologous tissues compared to heterologous tissues. The objectives of the present study were to apply a stringent decellularization process to demineralized bone matrix (DBM), prepared from bovine bone, and to characterise the structure and composition of the resulting ECM materials and DBM itself. Additionally, we sought to produce a soluble form of DBM and ECM which could be induced to form a hydrogel. Current clinical delivery of DBM particles for treatment of bone defects requires incorporation of the particles within a carrier liquid. Differences in osteogenic activity, inflammation and nephrotoxicity have been reported with various carrier liquids. The use of hydrogel forms of DBM or ECM may reduce the need for carrier liquids. DBM and ECM hydrogels exhibited sigmoidal gelation kinetics consistent with a nucleation and growth mechanism, with ECM hydrogels characterised by lower storage moduli than the DBM hydrogels. Enhanced proliferation of mouse primary calvarial cells was achieved on ECM hydrogels, compared to collagen type I and DBM hydrogels. These results show that DBM and ECM hydrogels have distinct structural, mechanical and biological properties and have potential for clinical delivery without the need for carrier liquids.

Concepts: Bone, Collagen, Extracellular matrix, Skeletal system, Cartilage, Tissues, Tissue, Type-I collagen

2

This study elucidates exposure-response relationships between performance of repetitive tasks, grip strength declines, and fibrogenic-related protein changes in muscles, and their link to inflammation. Specifically, we examined forearm flexor digitorum muscles for changes in connective tissue growth factor (CTGF; a matrix protein associated with fibrosis), collagen type I (Col1; a matrix component), and transforming growth factor beta 1 (TGFB1; an upstream modulator of CTGF and collagen), in rats performing one of two repetitive tasks, with or without anti-inflammatory drugs.

Concepts: Bone, Blood, Collagen, Muscle, Myosin, Connective tissue, Growth factors, Type-I collagen

1

While collagen type I (Col-I) is commonly used as a structural component of biomaterials, collagen type III (Col-III), another fibril forming collagen ubiquitous in many soft tissues, has not previously been used. In the present study, the novel concept of an injectable hydrogel with semi-interpenetrating polymeric networks of heterotypic collagen fibrils, with tissue-specific Col-III to Col-I ratios, in a glycol-chitosan matrix was investigated. Col-III was introduced as a component of the novel hydrogel, inspired by its co-presence with Col-I in many soft tissues, its influence on the Col-I fibrillogenesis in terms of diameter and mechanics, and its established role in regulating scar formation. The hydrogel has a nano-fibrillar porous structure, and is mechanically stable under continuous dynamic stimulation. It was found to provide a longer half-life of about 35 days than similar hyaluronic acid-based hydrogels, and to support cell implantation in terms of viability, metabolic activity, adhesion and migration. The specific case of pure Col-III fibrils in a glycol-chitosan matrix was investigated. The proposed hydrogels meet many essential requirements for soft tissue engineering applications, particularly for mechanically challenged tissues such as vocal folds and heart valves.

Concepts: Protein, Scar, Collagen, Soft tissue sarcoma, Tissues, Novel, Soft tissue, Type-I collagen