Evaluation of platelet-rich fibrin versus collagen membrane for enhancing healing of secondary grafted alveolar cleft: a randomised controlled trial.

The purpose of this study was to compare the efficiency of using autologous platelet-rich fibrin versus a resorbable collagen membrane in secondary alveolar bone grafting. Patients were randomly allocated to the three treatment groups: Group 1 - twelve children in whom the nasal layers of the alveolar clefts were repaired using autologous platelet-rich fibrin with autogenous chin bone; Group 2 - twelve children in whom the nasal layers of the alveolar clefts were repaired using bovine collagen membrane type I (Colla-D) with autogenous chin bone; and Group 3 - twelve children in whom the bony alveolar clefts were grafted with autogenous chin bone after construction of a watertight nasal floor had been completed. The study population comprised 36 patients with alveolar clefts, ranging in age from seven to 12 years. At the last follow-up period all groups had stable healing conditions and good radiological outcomes in terms of the alveolar bone height bordering the teeth (both mesially and distally) and the incorporation of grafting material with the surrounding bone. The use of either a PRF membrane and a collagen membrane as an interpositional layer between the nasal layer and the autogenous chin bone graft enhanced bone formation and density in alveolar clefts compared with the control group.

Alantolactone Attenuates Renal Fibrosis via Inhibition of Transforming Growth Factor ß/Smad3 Signaling Pathway.

BACKGRUOUND: Renal fibrosis is characterized by the accumulation of extracellular matrix proteins and interstitial fibrosis. Alantolactone is known to exert anticancer, anti-inflammatory, antimicrobial and antifungal effects; however, its effects on renal fibrosis remains unknown. Here, we investigated whether alantolactone attenuates renal fibrosis in mice unilateral ureteral obstruction (UUO) and evaluated the effect of alantolactone on transforming growth factor (TGF) signaling pathway in renal cells. METHODS: To evaluate the therapeutic effect of alantolactone, cell counting kit-8 (CCK-8) assay, histological staining, Western blot analysis, and real-time quantitative polymerase chain reaction were performed in UUO kidneys in vivo and in TGF-ß-treated renal cells in vitro. RESULTS: Alantolactone (0.25 to 4 µM) did not affect the viability of renal cells. Mice orally administered 5 mg/kg of alantolactone daily for 15 days did not show mortality or liver toxicity. Alantolactone decreased UUO-induced blood urea nitrogen and serum creatinine levels. In addition, it significantly alleviated renal tubulointerstitial damage and fibrosis and decreased collagen type I, fibronectin, and α-smooth muscle actin (α-SMA) expression in UUO kidneys. In NRK-49F cells, alantolactone inhibited TGF-ßstimulated expression of fibronectin, collagen type I, plasminogen activator inhibitor-1 (PAI-1), and α-SMA. In HK-2 cells, alantolactone inhibited TGF-ß-stimulated expression of collagen type I and PAI-1. Alantolactone inhibited UUO-induced phosphorylation of Smad3 in UUO kidneys. In addition, it not only decreased TGF-ß secretion but also Smad3 phosphorylation and translocation to nucleus in both kidney cell lines. CONCLUSION: Alantolactone improves renal fibrosis by inhibiting the TGF-ß/Smad3 signaling pathway in obstructive nephropathy. Thus, alantolactone is a potential therapeutic agent for chronic kidney disease.

Study on the molecular mechanism of dihydromyricetin in alleviating liver cirrhosis based on network pharmacology.

Dihydromyricetin (DHM) is a bioactive flavonoid extracted from Hovenia dulcis, which has various activities. In the present study, the molecular mechanism of dihydromyricetin (DHM) in relieving liver cirrhosis was investigated through network pharmacology and experimental verification. The cell model was induced by TGF-ß1 activating the human hepatic stellate cell line (HSC; LX-2). The protein levels of α-SMA, collagen I, and collagen III and pathway-related proteins within LX-2 cells were detected using Western blot. EdU staining was conducted to detect cell proliferation. Immunofluorescence staining was performed to detect the expression levels of α-SMA and collagen I. Next, the drug targets of DHM were screened from the PubChem database. The differentially expressed genes in the liver cirrhosis dataset GSE14323 were identified. The expression of the identified drug targets in LX-2 cells was verified using qRT-PCR. The results showed that TGF-ß1 treatment notably increased LX-2 cell viability, promoted cell proliferation, and elevated α-SMA, collagen I, and collagen III protein contents. DHM treatment could partially eliminate TGF-ß1 effects, as evidenced by the inhibited cell viability and proliferation and reduced α-SMA, collagen I, and collagen III contents. After network pharmacology analysis, nine differentially expressed target genes (MMP2, PDGFRB, PARP1, BCL2L2, ABCB1, TYR, CYP2E1, SQSTM1, and IL6) in liver cirrhosis were identified. According to qRT-PCR verification, DHM could inhibit the expression of MMP2, PDGFRB, PARP1, CYP2E1, SQSTM1, and IL6, and enhance ABCB1 expression levels within LX-2 cells. Moreover, DHM inhibited mTOR and MAPK signaling pathways in TGF-ß1-induced HSCs. In conclusion, DHM could inhibit HSC activation, which may be achieved via acting on MMP2, PDGFRB, PARP1, CYP2E1, SQSTM1, IL6, and ABCB1 genes and their downstream signaling pathways, including mTOR and MAPK signaling pathway.

Effects of ultra-low dose hormone therapy on biochemical bone turnover markers in postmenopausal women: A randomized, placebo-controlled, double-blind trial.

OBJECTIVE: Evaluate the effects of ultra-low-dose hormone therapy (Ultra-LD HT) with 17ß-estradiol 0.5 mg and norethisterone acetate 0.1 mg (E2 0.5/NETA 0.1) versus placebo on bone turnover markers (BTM) in postmenopausal women. STUDY DESIGN: A multicenter, double-blind, randomized, placebo-controlled study was performed with 107 participants who received one tablet daily of E2 0.5/NETA 0.1 or placebo for 24-weeks. Bone formation markers-N-terminal propeptide of type I procollagen (PINP) and Bone-specific alkaline phosphatase (BSAP), and bone resorption markers-C-telopeptide of type I collagen (CTX-I) and N-telopeptide crosslinked of type I collagen (NTX) were assessed before and at 12 and 24-weeks of treatment. RESULTS: Women treated with E2 0.5/NETA 0.1 had a significant reduction in the PINP marker from baseline (58.49 ± 21.12 µg/L) to week 12 (48.31 ± 20.99 µg/L) and week 24 (39.16 ± 16.50 µg/L). Placebo group, the PINP marker did not differ significantly. The analysis of the BSAP indicated a significant increase in the placebo group (13.8 ± 5.09 µg/L and 16.29 ± 4.3 µg/L, at baseline and week 24, respectively), whereas in the treatment group the values did not change. The analysis of the NTX marker showed a significant reduction only in the treatment group (43.21 ± 15.26 nM/mM and 33.89 ± 14.9 nM/mM, at baseline and week 24, respectively). CTX-I had a significant decrease in the treatment group from baseline (0.3 ± 0.16 ng/L) to week 12 (0.21 ± 0.14 ng/L) and week 24 (0.21 ± 0.12 ng/L). CONCLUSION: Women receiving E2 0.5/NETA 0.1 experienced reductions in bone resorption and formation markers, an expected effect during the anti-resorptive therapy, suggesting a protective bone effect with the Ultra-LD HT.

Cell-free cartilage repair in large defects of the knee: increased failure rate 5 years after implantation of a collagen type I scaffold.

INTRODUCTION: Cartilage defects of the knee remain a challenging problem in orthopedic surgery despite the ongoing improvements in regenerative procedures such as the autologous chondrocyte transplantation. Due to the lack of donor-site morbidity and the single-stage procedure cell-free scaffolds are an interesting alternative to cell-based procedures. But as currently mid- and long-term data are lacking, the aim of the present study was to present mid-term clinical, radiological and histological results of a cell-free collagen type I scaffolds for cartilage repair. MATERIALS AND METHODS: Twenty-eight patients were followed prospectively. Clinical evaluation using patient-reported outcome measures (KOOS, IKDC; VAS for pain, Tegner score for activity) as well as radiologic evaluation of the repair tissue (MOCART) was performed at 1 year, 2 years and 5 years. Histologic evaluation of the repair tissue was done in case of revision surgery using the ICRS II score for human cartilage repair. RESULTS: In these large cartilage defects with a mean defect size of 3.7 ± 1.9 cm2, clinical failure necessitating revision surgery was seen in 5 of 28 patients (18%). While the remaining patients showed good-to-excellent clinical results (KOOS, IKDC, VAS, Tegner), the radiologic appearance of the repair tissue showed a reduction of the MOCART score between the 2- and 5-year follow-up. Histologic evaluation of the repair tissue showed a cartilage-like appearance with no signs of inflammation or cell death but an overall medium tissue quality according to the ICRS II Score. CONCLUSION: The use of this cell-free collagen type I scaffold for large defects showed increased wear of the repair tissue and clinical failure in 18% of cases at 5-year follow-up.

Gene Therapy with Tetracycline-Regulated Human Recombinant COLIA1 cDNA Direct Adenoviral Delivery Enhances Fracture Healing in Osteoporotic Rats.

A number of previous studies have indicated that the genetic variation at the collage type I alpha 1 (COLIA1) gene locus influences susceptibility to osteoporosis. However, seldom have studies reported the effect of gene delivery using an adenovirus vector carrying human recombinant COLIA1 cDNA on stimulating osteogenic activity of osteoblasts and enhancing fracture healing of ovariectomized rats. The current study was performed to demonstrate whether direct gene delivery using an adenovirus vector carrying human recombinant COLIA1 cDNA could stimulate osteogenic activity of osteoblast in vitro and enhance fracture healing of ovariectomized rats in vivo. In vitro, the tet-on system regulated COLIA1 gene adenovirus was constructed and transfected to osteoblasts. COLIA1 mRNA and collagen type I levels were assessed by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay to determine whether adenovirus transfected successfully. Osteogenic activity of the osteoblasts was assessed by alkaline phosphatase activity, immunohistochemical staining, immunofluorescent staining, mineralized matrix formation, and extracellular calcium levels. In vivo, adenovirus-delivered COLIA1 gene was injected into the fracture site of the tibia in an ovariectomized rat model of osteoporosis, and bone callus condition was assessed to determine whether the COLIA1 gene could accelerate osteoporotic fracture healing. In vitro, the results showed that COLIA1 gene adenovirus transfection could increase osteoblast COLIA1 gene expression and collagen type I protein synthesis, increase alkaline phosphatase activity, and stimulate calcium nodules formation, which exhibited a direct osteogenic effect on the osteoblasts. In vivo, local injection of COLIA1 gene adenovirus increased collagen type I expression, restored bone mineral density, and accelerated fracture healing in ovariectomized rats, without increasing serum collagen type I and liver COLIA1 mRNA levels. This study suggests direct gene delivery using an adenovirus carrying human COLIA1 cDNA can stimulate the osteogenic activity of osteoblasts in vitro and enhance bone fracture healing in vivo. The tet-on system is an ideal gene regulatory system for effective and safe regulation of the therapeutic gene.

Collagen Type 1 Accelerates Healing of Ruptured Fetal Membranes.

Preterm premature rupture of membranes (pPROM) is a major cause of preterm birth. Recently, extracellular matrix-directed treatment is applied for wound healing. Here, we used a pregnant mouse model to test the efficacy of collagen type 1 gel for healing of the prematurely ruptured fetal membranes. Although injection of PBS into the ruptured fetal membranes resulted in 40% closure, injection of collagen type 1 improved closure rates to 90% within 72 h. Macrophages of the M2 wound healing phenotype were entrapped in the collagen layer. In primary human amnion mesenchymal cells, collagen type 1 gels activated collagen receptor discoidin domain receptor 2 (DDR2) to induce myosin light chain phosphorylation and migration of injured amnion mesenchymal cells. These findings define the mechanisms for matrix-directed therapeutics for pPROM.

Good clinical results with autologous matrix-induced chondrogenesis (Amic) technique in large knee chondral defects.

PURPOSE: Autologous matrix-induced chondrogenesis (AMIC) is a treatment for focal full-thickness cartilage defects combining microfracturing with an exogenous I/III collagen matrix (Chondro-Gide). The aim of the present study was to determine the 7 years outcomes of patients treated with the AMIC technique for knee chondral defects larger than 2 cm2. The hypothesis was that the positive short-term outcomes achieved in the previous series would not deteriorate at a 7-year follow-up. METHODS: Twenty-one patients treated with the AMIC technique were retrospectively analysed. Patients were assessed through the IKDC subjective knee evaluation questionnaire and the Lysholm scoring system. All patients underwent a complete imaging study including radiographs and magnetic resonance. The median defect size was found to be 4.3 (range 2.9-8) cm2. RESULTS: At a median follow-up of 7 (±1.4) years, the mean IKDC score improved from 31.7 (±8.9) points preoperatively, to 80.6 (±5.3) at the latest follow-up (p < 0.05). The mean Lysholm score improved from 38.8 (±12.4) points preoperatively to 72.6 (±19.5) points at the last follow-up (p < 0.05). At the last follow-up, 76.2% of patients were satisfied or extremely satisfied with their outcomes, while 66.6% of patients showed good quality repair tissue on magnetic resonance imaging. CONCLUSION: AMIC was found to be an effective method to treat full-thickness knee chondral defects larger than 2 cm2, with significant clinical and functional improvement maintained over a 7-year follow-up. LEVEL OF EVIDENCE: IV.

Lumbar fusion with collagen type I and polyvinylpyrrolidone in combination with autograft. An experimental study in New Zealand rabbits.

INTRODUCTION: Multiple strategies have been developed looking for upgrading the consolidation rate of spine arthrodesis with autolog bone graft, but no evidence exists that adhesion with Collagen type 1 and polyvinylpyrrolidone (FibroquelMR) have application on this field. OBJECTIVE: Determine if collagen type 1 + Polyvinylpyrrolidone are effective as bone enhancer in posterolateral arthrodesis on rabbits. METHOD: Posterolateral arthrodesis in 15 New Zealand rabbits on level L5-L6 using autolog bone graft in left side (control group) and autolog bone graft + 1 ml FibroquelMR (study group) in right side of arthrodesis. Euthanasia and block resection of lumbar segment eight weeks post surgery. Radiographic analysis, manual exploration and light microscopy of fussed segments. RESULTS: Radiographic consolidation was observed in 80% in control group and 95% in study group, interleaved trabecular pattern with bone continuity and normal characteristics in 12 left sides and 14 right sides. CONCLUSION: Collagen type 1 and polyvinylpyrrolidone use is likely to have positive effect in bone consolidation process, therefore it can be recommended to use it as a bone enhancer.

INTRODUCCIÓN: Existen diversas estrategias para aumentar la tasa de consolidación de la artrodesis de columna en presencia de injerto óseo autólogo, sin aún comprobar si la adhesión de Colágena tipo I y polivinilpirrolidona (FibroquelMR) tienen aplicaciones en este campo. OBJETIVO: Determinar la efectividad de la colágena tipo I con polivinilpirrolidona como potenciador óseo en artrodesis posterolateral de conejos. MÉTODOS: Artrodesis posterolateral en 15 conejos de Nueva Zelanda L5-L6 colocando injerto autólogo del lado izquierdo (Control) e injerto autólogo + 1 ml FibroquelMR (Estudio) en el lado derecho de la artrodesis. Eutanasia con resección en bloque del segmento lumbar a las ocho semanas del postoperatorio. Análisis radiográfico, palpación manual y por microscopia de luz de los segmentos fusionados. RESULTADOS: Se observó consolidación radiográfica en 80% en grupo control y 93% en el estudio, continuidad ósea con patrón trabecular intercalado y hueso de características normales en 12 del lado izquierdo y 14 en el lado derecho. CONCLUSIONES: La utilización de Colágena tipo I y polivinilpirrolidona puede tener efectos positivos en el proceso de consolidación ósea por lo que se puede recomendar su utilización como reforzador óseo.

Lumbar fusion with collagen type I and polyvinylpyrrolidone in combination with autograft. An experimental study in New Zealand rabbits / Colágena tipo I y polivinilpirrolidona en combinación con autoinjerto para artrodesis lumbar. Estudio experimental en conejos de Nueva Zelanda

Abstract: Introduction: Multiple strategies have been developed looking for upgrading the consolidation rate of spine arthrodesis with autolog bone graft, but no evidence exists that adhesion with Collagen type 1 and polyvinylpyrrolidone (FibroquelMR) have application on this field. Objective: Determine if collagen type 1 + Polyvinylpyrrolidone are effective as bone enhancer in posterolateral arthrodesis on rabbits. Method: Posterolateral arthrodesis in 15 New Zealand rabbits on level L5-L6 using autolog bone graft in left side (control group) and autolog bone graft + 1 ml FibroquelMR (study group) in right side of arthrodesis. Euthanasia and block resection of lumbar segment eight weeks post surgery. Radiographic analysis, manual exploration and light microscopy of fussed segments. Results: Radiographic consolidation was observed in 80% in control group and 95% in study group, interleaved trabecular pattern with bone continuity and normal characteristics in 12 left sides and 14 right sides. Conclusion: Collagen type 1 and polyvinylpyrrolidone use is likely to have positive effect in bone consolidation process, therefore it can be recommended to use it as a bone enhancer.

Resumen: Introducción: Existen diversas estrategias para aumentar la tasa de consolidación de la artrodesis de columna en presencia de injerto óseo autólogo, sin aún comprobar si la adhesión de Colágena tipo I y polivinilpirrolidona (FibroquelMR) tienen aplicaciones en este campo. Objetivo: Determinar la efectividad de la colágena tipo I con polivinilpirrolidona como potenciador óseo en artrodesis posterolateral de conejos. Métodos: Artrodesis posterolateral en 15 conejos de Nueva Zelanda L5-L6 colocando injerto autólogo del lado izquierdo (Control) e injerto autólogo + 1 ml FibroquelMR (Estudio) en el lado derecho de la artrodesis. Eutanasia con resección en bloque del segmento lumbar a las ocho semanas del postoperatorio. Análisis radiográfico, palpación manual y por microscopia de luz de los segmentos fusionados. Resultados: Se observó consolidación radiográfica en 80% en grupo control y 93% en el estudio, continuidad ósea con patrón trabecular intercalado y hueso de características normales en 12 del lado izquierdo y 14 en el lado derecho. Conclusiones: La utilización de Colágena tipo I y polivinilpirrolidona puede tener efectos positivos en el proceso de consolidación ósea por lo que se puede recomendar su utilización como reforzador óseo.

Lingual Nerve Microsurgery Outcomes Using 2 Different Conduits: A Retrospective Cohort Study.

PURPOSE: This study compared a type 1 collagen conduit (NeuraGen) with a porcine small intestinal submucosa conduit (AxoGuard) when used in lingual nerve microsurgery and any differences in achieving functional sensory recovery (FSR). PATIENTS AND METHODS: All patients who underwent lingual nerve microsurgery performed by 1 surgeon (V.B.Z.) from 2007 to 2014 had their surgical information obtained by a retrospective review of hospital records and office charts after institutional review board approval. Those patients whose surgery included the use of a nerve conduit were included in the study. Subjective neurosensory recovery was determined by neurosensory testing, including responses to hot, cold, wisp, brush, and pinprick. Objective recovery was determined by testing 2-point discrimination and fine touch threshold with von Frey fibers. The objective findings were correlated to a Medical Research Council System score, with grades S3, S3+, and S4 indicating FSR. RESULTS: The conduits were compared using a Student t test with a 2-tailed hypothesis. The von Frey fiber test had a preoperative mean of 6.29 (standard deviation [SD], 0.95), which improved to 3.97 (SD, 0.67) for the NeuraGen and 4.17 (SD, 0.56) for the AxoGuard. Two-point discrimination improved from a mean higher than 19.42 to 9.32 mm (SD, 2.96 mm) for the NeuraGen and 9.67 mm (SD, 2.13 mm) for the AxoGuard. The mean FSR was S3+. CONCLUSIONS: There were no meaningful differences in outcomes between the 2 conduits studied, and all patients achieved FSR according to the Medical Research Council Scale.

Human Bone Derived Collagen for the Development of an Artificial Corneal Endothelial Graft. In Vivo Results in a Rabbit Model.

Corneal keratoplasty (penetrating or lamellar) using cadaveric human tissue, is nowadays the main treatment for corneal endotelial dysfunctions. However, there is a worldwide shortage of donor corneas available for transplantation and about 53% of the world's population have no access to corneal transplantation. Generating a complete cornea by tissue engineering is still a tough goal, but an endothelial lamellar graft might be an easier task. In this study, we developed a tissue engineered corneal endothelium by culturing human corneal endothelial cells on a human purified type I collagen membrane. Human corneal endothelial cells were cultured from corneal rims after corneal penetrating keratoplasty and type I collagen was isolated from remnant cancellous bone chips. Isolated type I collagen was analyzed by western blot, liquid chromatography -mass spectrometry and quantified using the exponentially modified protein abundance index. Later on, collagen solution was casted at room temperature obtaining an optically transparent and mechanically manageable membrane that supports the growth of human and rabbit corneal endothelial cells which expressed characteristic markers of corneal endothelium: zonula ocluddens-1 and Na+/K+ ATPase. To evaluate the therapeutic efficiency of our artificial endothelial grafts, human purified type I collagen membranes cultured with rabbit corneal endothelial cells were transplanted in New Zealand white rabbits that were kept under a minimal immunosuppression regimen. Transplanted corneas maintained transparency for as long as 6 weeks without obvious edema or immune rejection and maintaining the same endothelial markers that in a healthy cornea. In conclusion, it is possible to develop an artificial human corneal endothelial graft using remnant tissues that are not employed in transplant procedures. This artificial endothelial graft can restore the integrality of corneal endothelium in an experimental model of endothelial dysfunction. This strategy could supply extra endothelial tissue and compensate the deficit of cadaveric grafts for corneal endothelial transplantation.

Type I collagen and its daughter peptides for targeting mucosal healing in ulcerative colitis: A new treatment strategy.

Ulcerative colitis, particularly the chronic persistent form is characterized by the presence of active inflammation and extensive areas of ulceration in the colonic mucosa. The existing treatment protocol aims at only reducing intestinal inflammation, rather than targeting mucosal ulceration. In this study, type I collagen and its daughter peptides called collagen hydrolysate, highly popular reconstructive materials for tissue engineering applications, are hypothesized as healing matrices to target the recuperation of internal mucosal ulceration. The clinical assessments on day 10 of dextran sodium sulfate induced colitis in mice model revealed that both the collagen (1.56±0.29) and collagen hydrolysate treatments (1.33±0.33) showed a significant reduction in the rectal bleeding compared to the reference mesalamine treatment (2.50±0.33) and untreated negative control (2.40±0.40). VEGF, a potent angiogenic growth factor, over expressed during UC was down-regulated by collagen hydrolysate (1.06±0.25) and collagen (1.76±0.45) to a greater extent than by mesalamine (2.59±0.51) and untreated control (4.17±0.15). The down-regulation of proinflammatory cytokines such as TNF-α, IL-1ß, and IL-6 also follows the same pattern. Histological observations were in accordance with the clinical indicators. Both collagen and collagen hydrolysate treatments showed significant reduction in mucosal damage score and facilitated faster regeneration of damaged mucosa.

Preclinical evaluation of collagen type I scaffolds, including gelatin-collagen microparticles and loaded with a hydroglycolic Calendula officinalis extract in a lagomorph model of full-thickness skin wound.

Previously, we have developed collagen type I scaffolds including microparticles of gelatin-collagen type I (SGC) that are able to control the release of a hydroglycolic extract of the Calendula officinalis flower. The main goal of the present work was to carry out the preclinical evaluation of SGC alone or loaded with the C. officinalis extract (SGC-E) in a lagomorph model of full-thickness skin wound. A total of 39 rabbits were distributed in three groups, of 13 animals each. The first group was used to compare wound healing by secondary intention (control) with wound healing observed when wounds were grafted with SGC alone. Comparison of control wounds with wounds grafted with SGC-E was performed in the second group, and comparison of wounds grafted with SGC with wounds grafted with SGC-E was performed in the third group. Clinical follow-ups were carried in all animals after surgery, and histological and histomorphometric analyses were performed on tissues taken from the healed area and healthy surrounding tissue. Histological and histomorphometric results indicate that grafting of SGC alone favors wound healing and brings a better clinical outcome than grafting SGC-E. In vitro collagenase digestion data suggested that the association of the C. officinalis extract to SGC increased the SGC-E cross-linking, making it difficult to degrade and affecting its biocompatibility.

Co-analgesic therapy for arthroscopic supraspinatus tendon repair pain using a dietary supplement containing Boswellia serrata and Curcuma longa: a prospective randomized placebo-controlled study.

BACKGROUND: The cuff tendon that is most prone to full-thickness rotator cuff tears is the supraspinatus (SSP). Arthroscopic SSP repair ensures good to satisfactory mid- to long-term clinical outcomes. However, the intense postoperative pain reduces rehabilitation compliance and is cause of patient dissatisfaction. Many natural compounds act by inhibiting inflammatory pathways in a similar way to anti-inflammatory drugs MATERIALS AND METHODS: This was a prospective randomized trial designed to assess the analgesic effect of a dietary supplement (DS) containing Boswellia serrata and Curcuma longa in a population of subjects with full-thickness SSP tendon tear treated by arthroscopy. Three weeks before surgery, patients were randomized to receive Tendisulfur(®) (group T) or a placebo (group P) for 2 months. The primary outcome measure was subjective VAS pain. Secondary outcomes measures were Constant-Murley score simple shoulder test, and patient global assessment (PGA) scores. Patients were assessed immediately at baseline and subsequently at 1, 2, 4, 6, 8, 12, and 24 weeks. RESULTS: Stratification of pain scores and subscores demonstrated significantly lower overall pain scores in group T versus group P at 1 week (p = 0.0477), and lower but not significantly different scores on week 2 (p = 0.0988); at subsequent time points, differences were not significant (p > 0.05). PGA scores were good in all subjects. CONCLUSIONS: In conclusion, this study provides objective data on the effect of a DS containing natural substances, added to standard analgesics, on postoperative RC pain. DS alleviated short and partially mid-term pain, while long-term pain was unchanged. This limitation can probably be addressed by a dosage increase over the first 4 weeks and by extending treatment by 1 or 2 months.

Prospective Randomized Controlled Trial of Hindfoot and Ankle Fusions Treated With rhPDGF-BB in Combination With a ß-TCP-Collagen Matrix.

BACKGROUND: Ankle and hindfoot arthrodesis is often supplemented with autograft to promote bony union. Autograft harvest can lead to increased perioperative morbidity. Purified recombinant human platelet-derived growth factor BB homodimer (rhPDGF-BB) has stimulated bone formation in mandibular defects and hindfoot fusion. This randomized controlled trial evaluated the efficacy and safety of rhPDGF-BB combined with an injectable, osteoconductive beta-tricalcium phosphate (ß-TCP)-collagen matrix versus autograft in ankle and hindfoot fusions. METHODS: Seventy-five patients requiring ankle or hindfoot fusion were randomized 5:1 for rhPDGF-BB/ß-TCP-collagen (treatment, n = 63) or autograft (control, n = 12). Prospective analysis included 142 autograft control subjects from another clinical trial with identical study protocols. Standardized operative and postoperative protocols were used. Patients underwent standard internal fixation augmented with autograft or 0.3 mg/mL rhPDGF-BB/ß-TCP-collagen. Radiologic, clinical, and quality-of-life outcomes were assessed over 52 weeks. Primary outcome was joint fusion (50% or more osseous bridging on computed tomography) at 24 weeks. Secondary outcomes included radiographs, clinical healing status, visual analog scale pain score, American Orthopaedic Foot & Ankle Society Ankle-Hindfoot Scale score, Foot Function Index score, and Short Form-12 score. Noninferiority P values were calculated. RESULTS: Complete fusion of all involved joints at 24 weeks as indicated by computed tomography was achieved in 53 of 63 (84%) rhPDGF-BB/ß-TCP-collagen-treated patients and 100 of 154 (65%) autograft-treated patients (P < .001). Mean time to fusion was 14.3 ± 8.9 weeks for rhPDGF-BB/ß-TCP-collagen patients versus 19.7 ± 11.5 weeks for autograft patients (P < .01). Clinical success at 52 weeks was achieved in 57 of 63 (91%) rhPDGF-BB/ß-TCP-collagen patients and 120 of 154 (78%) autograft patients (P < .001). Safety-related outcomes were equivalent. Autograft controls had 2 bone graft harvest infections. CONCLUSIONS: Application of rhPDGF-BB/ß-TCP-collagen was a safe, effective alternative to autograft for ankle and hindfoot fusions, eliminating the pain and morbidity associated with autograft harvesting. LEVEL OF EVIDENCE: Level I, prospective randomized study.

Effects of oral administration of tripeptides derived from type I collagen (collagen tripeptide) on atherosclerosis development in hypercholesterolemic rabbits.

Digestion of type I collagen with a collagenase-type protease yields a collagen tripeptide (Ctp) fraction comprising Gly-X-Y sequences that exhibit diverse biological activities. We previously demonstrated that Ctp inhibits the proliferation and migration of cultured aortic smooth muscle cells (SMCs) in vitro. These cells contribute to the pathogenesis of atherosclerosis and other cardiovascular diseases. In order to evaluate the effects of Ctp on atherosclerosis development in vivo, here we used the Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbit model of familial hypercholesterolemia to determine the effects of oral administration of Ctp for three months. Ctp induced a significant decrease in the area occupied by atherosclerotic plaques in the aorta and in the level of total serum cholesterol. The components of atherosclerotic plaques underwent distinct changes, including reduction in the populations of macrophages and SMCs and a significant decrease in the proportion of macrophages to SMCs. Ctp administration decreased the number of cells in plaques that expressed proliferating cell nuclear antigen and the number of cells with oxidative damage to DNA as indicated by 8-hydroxy-2'-deoxyguanine detection. These findings are the first to define the mechanism underlying the inhibitory effects of Ctp on atherosclerosis development in hypercholesterolemic rabbits, and suggest that Ctp provides an effective therapy for treating atherosclerosis.

Functional improvement following implantation of a microstructured, type-I collagen scaffold into experimental injuries of the adult rat spinal cord.

The formation of cystic cavitation following severe spinal cord injury (SCI) constitutes one of the major barriers to successful axonal regeneration and tissue repair. The development of bioengineered scaffolds that assist in the bridging of such lesion-induced gaps may contribute to the formulation of combination strategies aimed at promoting functional tissue repair. Our previous in vitro investigations have demonstrated the directed axon regeneration and glial migration supporting properties of microstructured collagen scaffold that had been engineered to possess mechanical properties similar to those of spinal cord tissues. Here, the effect of implanting the longitudinally orientated scaffold into unilateral resection injuries (2mm long) of the mid-cervical lateral funiculus of adult rats has been investigated using behavioural and correlative morphological techniques. The resection injuries caused an immediate and long lasting (up to 12 weeks post injury) deficit of food pellet retrieval by the ipsilateral forepaw. Implantation of the orientated collagen scaffold promoted a significant improvement in pellet retrieval by the ipsilateral forepaw at 6 weeks which continued to improve up to 12 weeks post injury. In contrast, implantation of a non-orientated gelatine scaffold did not result in significant functional improvement. Surprisingly, the improved motor performance was not correlated with the regeneration of lesioned axons through the implanted scaffold. This observation supports the notion that biomaterials may support functional recovery by mechanisms other than simple bridging of the lesion site, such as the local sprouting of injured, or even non-injured fibres.

Stage-two surgery using collagen soft tissue grafts: clinical cases and ultrastructural analysis.

OBJECTIVE: To present the application of two different soft tissue grafts around dental implants during stage-two surgery. Furthermore, the ultrastructure of these materials is shown and discussed using scanning electron microscopy (SEM). SUMMARY: Although soft tissue autografts may be currently regarded as the gold standard, harvesting of these grafts might lead to higher morbidity, longer chair time, and intra-/postoperative complications at the donor site. New developments in collagen scaff olds have provided an alternative to successfully replace autologous grafts in clinical practice. The SEM pictures clearly show the different composition of a bilayer scaff old (collagen matrix, CM) and a porcine acellular dermal matrix (ADM). These distinctive properties lead to different possible indications. Within the presented cases, ADM was used to augment the ridge contour and was placed into a buccal pouch to achieve complete coverage and an uneventful closed healing. On the other side, CM was left exposed to the oral cavity to successfully gain keratinized mucosa around and between two dental implants.

Future treatment strategies for cartilage repair.

This article presents the advances in cartilage repair from improvements in current therapies to promising therapies using growth factors, scaffolds, and cellular therapy. These are strategies that will likely lead to promising clinical applications.