Collagen Deposition and Inflammatory Response Associated with Macroporous Mesh Shrinkage in Incisional Hernia Repair: A Rat Model.

Background: Mesh repair is the current recommendation for the treatment of incisional hernia; however, the best mesh has yet to be determined. The objective of this study was to compare the inflammatory response and collagen deposition in primary incisional hernia repair (P) and different macroporous mesh materials, including polypropylene with poliglecaprone (PP-PG), polyvinylidene fluoride (PVDF), and polyester (PE), using quantitative methods. Methods: Sixty male rats were divided into four groups. Anterior abdominal wall defects were created and either suture or mesh repair was done. Rats were euthanized on days 14, 90, and 180, and the gross findings were recorded. The inflammatory and collagen levels in the abdominal wall tissues were measured using enzyme-linked immunosorbent assay (ELISA). Results: The PE group demonstrated significant mesh shrinkage at 180 days. The extent of PE mesh shrinkage ranged from 22-42% (mean = 30.49%). At 14 days, the PVDF group had higher interleukin-6 (IL-6) levels than the PP-PG (P = .004) and PE groups (P = .019). At 90 days, the collagen type I (Col I) levels in the PE group were significantly lower than those in the others, and the collagen type I/III (Col I/III) ratios in the PE group were lower than those in the P group (P = .006). Conclusions: The persistently high IL-6 levels until 180 days and the decrease in Col I levels and Col I/III ratio at 90 days seem to predict mesh shrinkage at 180 days. The mesh induces high Col I levels, but those associated with low Col III levels should be preferred.

Picrosirius Red Staining: Revisiting Its Application to the Qualitative and Quantitative Assessment of Collagen Type I and Type III in Tendon.

Collagen has a major role in the structural organization of tendons. Picrosirius red (PSR) staining viewed under polarized light microscopy is the standard method to evaluate the organization of collagen fibers in tissues. It is also used to distinguish between type I and type III collagen in tissue sections. However, accurate analysis and interpretation of PSR images are challenging because of technical factors and historical misconceptions. The aim of this study was to clarify whether collagen types I and III can be distinguished by PSR staining in rat Achilles tendons, using double immunohistochemistry as the positive control. Our findings showed that PSR staining viewed with polarized light microscopy was suitable for qualitative and quantitative assessment of total collagen but was not able to distinguish collagen types. We found it critical to use a polarizing microscope equipped with a rotating stage; tendon section orientation at 45° with respect to crossed polarizers was optimal for the qualitative and quantitative assessment of collagen organization. Immunohistochemistry was superior to PSR staining for detection of collagen type III. We also compared formalin and Bouin solution as fixatives. Both produced similar birefringence, but formalin-fixed tendons provided higher quality histological detail with both hematoxylin-eosin and immunostaining.

Prognostic value of blood-based fibrosis biomarkers in patients with metastatic colorectal cancer receiving chemotherapy and bevacizumab.

A desmoplastic colorectal cancer stroma, characterized by excess turnover of the cancer-associated fibroblast derived collagens type III and VI, can lead to reduced drug-uptake and poor treatment response. We investigated the association between biomarkers of collagen type III and VI and overall survival (OS) in patients with metastatic colorectal cancer (mCRC). Serum samples were collected from 252 patients with mCRC prior to treatment with bevacizumab and chemotherapy. Serum concentrations of biomarkers reflecting formation of collagen type III (PRO-C3) and VI (PRO-C6) and degradation of collagen type VI (C6M and C6Mα3) were determined by ELISA. The biomarkers were evaluated for associations with OS, individually, combined, and after adjusting for carcinoembryonic antigen (CEA), lactate dehydrogenase (LDH) and performance status (PS). High baseline levels (> median) of each collagen biomarker were significantly associated with shorter OS (PRO-C3: HR = 2.0, 95%CI = 1.54-2.63; PRO-C6: HR = 1.6, 95%CI = 1.24-2.11; C6M: HR = 1.4, 95%CI = 1.05-1.78; C6Mα3: HR = 1.6, 95%CI = 1.16-2.07). PRO-C3 and PRO-C6 remained significant after adjustment for CEA, LDH and PS. Weak correlations were seen between the collagen biomarkers (r = 0.03-0.59) and combining all improved prognostic capacity (HR = 3.6, 95%CI = 2.30-5.76). Collagen biomarkers were predictive of shorter OS in patients with mCRC. This supports that collagen- and CAF biology is important in CRC.

Collagen I and III ratios and tenacity of rats muscle injured and treated with platelet-rich plasma / Relaciones de colágeno I y III y tenacidad del músculo de rata lesionado y tratado con plasma rico en plaquetas

SUMMARY: Severe muscle injuries are common in accidents and have a delayed recovery of muscle integrity. In these cases, muscle suture surgery is the standard treatment. However, Platelet Rich Plasma (PRP), has been widely used in orthopedic injuries due to its growth factors. Thus, the objective of the study will be to analyze the association of suture and PRP techniques in the collagen and tenacity of the injured muscle. Were used seventy rats, divided into five groups: control (C), injury control (CI), injury and suture (IS), injury and PRP (IP), injury, suture, and PRP (ISP). Were sectioned approximately 50 % of the width and 100 % of the thickness of the gastrocnemius muscle. The homologous PRP was applied 24h after the injury. On the 7th day after the injury, the animals were euthanized and their muscles subjected to mechanical testing to measure tenacity or collagen analysis to calculate the ratio between type I and III collagen. The results show a significant decrease (p <0.05) in the values of the relationship between collagens in all injured groups (CI, IS, IP, ISP) compared to group C. In injured groups, the tenacity was significantly (p <0.05) reduced compared to the control group, with no observed difference between treatments and injured groups. The amount of collagen in the injured area has increased, but it did not affect the tenacity of the muscles, which was reduced.

RESUMEN: Las lesiones musculares graves son comunes durante los accidentes y la integridad del músculo está sujeta a una larga recuperación. En esos casos la cirugía, para la sutura del músculo, es el tratamiento común, no obstante el plasma rico en plaquetas (PRP) ha sido utilizado recientemente en lesiones ortopédicas, debido a sus factores del crecimiento. El objetivo del estudio fue analizar la asociación de las técnicas de sutura y PRP en la histología y tenacidad de músculo lesionado. Fueron utilizadas 70 ratas distribuidas en cinco grupos: control (C), control lesión (CL), lesión y sutura (LS), lesión y PRP (LPRP), lesión, sutura y PRP (LSPRP). Aproximadamente en la lesión, el 50 % de la longitud y el 100 % del espesor del músculo gastrocnemio fueron seccionados. El PRP homólogo fue aplicado 24 horas después de la lesión. En el 7º día después de la lesión los animales fueron eutanasiados y las muestras fueran sometidas al ensayo mecánico para la medición de la tenacidad y análisis del colágeno, para realizar el cálculo de la relación entre los colágenos I y III. Los resultados demostraron una reducción significativa (p<0,05) en los valores de la relación entre los colágenos en todos los grupos lesionados en relación al grupo C. La tenacidad fue (p<0,05) reducida significativamente en los grupos lesionados en relación al grupo control, sin diferencia entre los tratados. En la lesión muscular hubo disminución de los valores de colágeno, aunque en los tratamientos se observó elevación de la cantidad de colágeno en la área lesionada, esta no tuvo efecto en la tenacidad de los músculos que fue disminuida en la lesión.

Distinct Expression Patterns of Fibrillar Collagen Types I, III, and V in Association with Mammary Gland Remodeling during Pregnancy, Lactation and Weaning.

The mammary gland structurally and functionally remodels during pregnancy, during lactation and after weaning. There are three types of fibrillar collagens, types I, III, and V, in mammary stromal tissue. While the importance of the fibrillar structure of collagens for mammary morphogenesis has been suggested, the expression patterns of each type of fibrillar collagen in conjunction with mammary remodeling remain unclear. In this study, we investigated their expression patterns during pregnancy, parturition, lactation and involution. Type I collagen showed a well-developed fibril structure during pregnancy, but the fibrillar structure of type I collagen then became sparse at parturition and during lactation, which was concurrent with the downregulation of its mRNA and protein levels. The well-developed fibrillar structure of type I collagen reappeared after weaning. On the other hand, type V collagen showed a well-developed fibrillar structure and upregulation in the lactation period but not in the periods of pregnancy and involution. Type III collagen transiently developed a dense fibrillar network at the time of parturition and exhibited drastic increases in mRNA expression. These results indicate that each type of fibrillar collagen is distinctly involved in structural and functional remodeling in mammary glands during pregnancy, parturition, lactation, and involution after weaning. Furthermore, in vitro studies of mammary epithelial cells showed regulatory effects of type I collagen on cell adhesion, cell proliferation, ductal branching, and ß-casein secretion. Each type of fibrillar collagen may have different roles in defining the cellular microenvironment in conjunction with structural and functional mammary gland remodeling.

Collagenofibrotic Glomerulopathy: Report a Rare Case.

Collagenofibrotic glomerulopathy is a rare clinical entity with fewer than 40 cases reported worldwide. We describe a case of adult onset nephrotic syndrome with partial villous atrophy of the intestine who was diagnosed with this rare entity. Collagenofibrotic glomerulopathy is characterized by subendothelial and mesangial collagen type III deposition and increased procollagen III peptide levels. Extra renal involvement has been described in the form of hypertension, anemia and microangiopathic hemolytic anemia but villous atrophy has not been associated with this condition so far, possibly reflecting the paucity of literature. We describe this case and review the condition in this report.

Effect of low intensity photobiomodulation associated with norbixin-based poly (hydroxybutyrate) membrane on post-tenotomy tendon repair. In vivo study.

PURPOSE: To evaluate the in vivo response of photobiomodulation therapy associated with norbixin-based poly(hydroxybutyrate) membrane (PHB) in tenotomized calcaneal tendon. METHODS: Thirty rats were randomly allocated to six groups (n=5 each): LED groups (L1, L2 and L3) and membrane + LED groups (ML1, ML2 and ML3). The right calcaneal tendons of all animals were sectioned transversely and were irradiated with LED daily, one hour after surgery every 24 hours, until the day of euthanasia. At the end of the experiments the tendons were removed for histological analysis. RESULTS: The histological analysis showed a significant reduction in inflammatory cells in the ML1, ML2 and ML3 groups (p=0.0056, p=0.0018 and p<0.0001, respectively) compared to those in the LED group. There was greater proliferation of fibroblasts in the ML1 (p<0.0001) and L3 (p<0.0001) groups. A higher concentration of type I collagen was also observed in the ML1 group (p=0.0043) replacing type III collagen. CONCLUSION: Photobiomodulation in association with norbixin-based PHB membrane led to control of the inflammatory process. However, it did not favor fibroblast proliferation and did not optimize type I collagen formation in the expected stage of the repair process.

Collagenofibrotic glomerulopathy - A rare disease diagnosed with the aid of transmission electron microscopy.

Collagenofibrotic glomerulopathy (CFG) is a rare idiopathic kidney disease characterized by abnormal deposition of atypical Type III collagen fibers in the glomerulus causing subendothelial and mesangial expansion, manifesting as progressive renal dysfunction accompanied by proteinuria. The majority of CFG cases reported in literature are from Japan where this disease entity was initially recognized. There is an increased awareness and diagnosis of this rare renal disease in India with the recent increase in utilization of electron microscopy (EM) in clinical diagnostic settings. We describe a 28-year-old Bangladeshi woman who presented with hypertension and nephrotic range proteinuria not amenable to treatment with steroids and cyclophosphamide, whose renal biopsy demonstrated diagnostic ultrastructural features of CFG. This illustrative case is presented to highlight the role of EM analysis for diagnostic accuracy in renal biopsy evaluation in addition to demonstrating the unusual renal biopsy findings of this rare entity.

Magnetic resonance imaging assessment of proteolytic enzyme concentrations and biologic properties of intraluminal thrombus in abdominal aortic aneurysms.

OBJECTIVE: The aim of the study was to determine whether magnetic resonance imaging (MRI) can be used in assessment of biologic activity of intraluminal thrombus (ILT) and proteolytic processes of the abdominal aortic aneurysm wall. METHODS: Using MRI, 50 patients with asymptomatic infrarenal abdominal aortic aneurysm were analyzed at the maximum aneurysm diameter on T1-weighted images in the arterial phase after administration of contrast material. Relative ILT signal intensity (SI) was determined as the ratio between ILT SI and psoas muscle SI. During surgery, the full thickness of the ILT and the adjacent part of the aneurysm wall were harvested at the maximal diameter for biochemical analysis. The concentrations of matrix metalloproteinase 9 and neutrophil elastase (NE/ELA) were analyzed in harvested thrombi, and the concentrations of collagen type III, elastin, and proteoglycans were analyzed in harvested aneurysm walls. RESULTS: A significant positive correlation was found between the NE/ELA concentration of the ILT and the relative SI (ρ = 0.309; P = .029). Furthermore, a negative correlation was observed between the elastin content of the aneurysm wall and the relative SI (ρ = -0.300; P = .034). No correlations were found between relative SI and concentration of matrix metalloproteinase 9, NE/ELA, collagen type III, or proteoglycan 4 in the aneurysm wall. CONCLUSIONS: These findings indicate a potential novel use of MRI in prediction of thrombus proteolytic enzyme concentrations and the extracellular matrix content of the aneurysm wall, thus providing additional information for the risk of potential aneurysm rupture.

Collagen type III nephropathy as a systemic disease? - A case report / Glomerulopatía por colágeno tipo III como enfermedad sistémica: caso clínico

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Effect of norbixin-based poly(hydroxybutyrate) membranes on the tendon repair process after tenotomy in rats.

PURPOSE: To determine the efficacy of norbixin-based poly(hydroxybutyrate) (PHB) membranes for Achilles tendon repair. METHODS: Thirty rats were submitted to total tenotomy surgery of the right Achilles tendon and divided into two groups (control and membrane; n = 15 each), which were further subdivided into three subgroups (days 7, 14, and 21; n = 5 each). Samples were analyzed histologically. RESULTS: Histological analysis showed a significant reduction in inflammatory infiltrates on days 7, 14 (p < 0.0001 for both), and 21 (p = 0.0004) in the membrane group compared to that in the control group. There was also a significant decrease in the number of fibroblasts in the control group on days 7, 14 (p < 0.0001), and 21 (p = 0.0032). Further, an increase in type I collagen deposition was observed in the membrane group compared to that in the control group on days 7 (p = 0.0133) and 14 (p = 0.0107). CONCLUSION: Treatment with norbixin-based PHB membranes reduces the inflammatory response, increases fibroblast proliferation, and improves collagen production in the tendon repair region, especially between days 7 and 14.

A Preliminary Report of the Biochemical and Clinical Effects of 1,4-Diaminobutane on Prevention of Human Hypertrophic Scars.

Objective evidence for the role of inhibition of collagen cross-linking in human scar using a nontoxic topical inhibitor, 1,4-diaminobutane (1,4 DAB), in patients with scars at risk for hypertrophic scar formation is presented. The authors used a concentration of 1,4 DAB of 0.8% (weight/volume) in a cream base similar to Glaxal Base. Application was once per day at night. The control was treated with cream base alone. In treatment phase studies at 2 months, tissue biopsies were performed and used to determine a therapeutic effect biochemically in paired scars harvested chosen with typical hypertrophic scars at two major treatment centers. Tissue transglutaminase activity revealed a significant reduction of the ε-(γ-glutamyl)lysine cross-links in the treated scars: 7.96 ± 1.51 pmol/µmol amino acid versus 14.78 ± 3.52 pmol/µmol amino acid. A subset of paired scars (n = 15) was also analyzed for soluble procollagen type III amino propeptide. The effect was a significant increase in procollagen type III amino propeptide in the scars treated with 1,4 DAB compared with sham-treated scars: 47.75 ± 4.6 µg/mg wet weight versus 39.08 ± 6.02 µg/mg wet weight, respectively. Levels of tissue 1,4 DAB was found to be twice as high in the presence of the active cream versus in the tissue of the control group. In subsequent prophylaxis studies, the authors treated 44 breast reduction patients prospectively with active cream to one or the other side in a double-blind randomized fashion. Hardness (in grams) measured using a Rex Durometer at 6 and 12 weeks postoperatively along with photographs were analyzed. The mean value ± SD of 24.98 ± 1.2 g on the active side versus 31.76 ± 1.1 g on the sham side was significantly different (p < 0.05). The patient scale scores of the Patient and Observer Scar Assessment Scale were also requested by survey in a responding 27-patient subgroup at a minimum 1 year postoperatively, and the differences between the two sides were found to be statistically significant, where the mean on the active side was 14.07 ± 1.34 and the mean on the sham side was 21.41 ± 1 (p < 0.05). The results are evidence to support the use of this agent in prevention of hypertrophic scars. CLINICAL QUESTION/LEVEL OF EVIDENCE:: Therapeutic, II.

Effect of low intensity photobiomodulation associated with norbixin-based poly (hydroxybutyrate) membrane on post-tenotomy tendon repair. In vivo study

Abstract Purpose: To evaluate the in vivo response of photobiomodulation therapy associated with norbixin-based poly(hydroxybutyrate) membrane (PHB) in tenotomized calcaneal tendon. Methods: Thirty rats were randomly allocated to six groups (n=5 each): LED groups (L1, L2 and L3) and membrane + LED groups (ML1, ML2 and ML3). The right calcaneal tendons of all animals were sectioned transversely and were irradiated with LED daily, one hour after surgery every 24 hours, until the day of euthanasia. At the end of the experiments the tendons were removed for histological analysis. Results: The histological analysis showed a significant reduction in inflammatory cells in the ML1, ML2 and ML3 groups (p=0.0056, p=0.0018 and p<0.0001, respectively) compared to those in the LED group. There was greater proliferation of fibroblasts in the ML1 (p<0.0001) and L3 (p<0.0001) groups. A higher concentration of type I collagen was also observed in the ML1 group (p=0.0043) replacing type III collagen. Conclusion: Photobiomodulation in association with norbixin-based PHB membrane led to control of the inflammatory process. However, it did not favor fibroblast proliferation and did not optimize type I collagen formation in the expected stage of the repair process.

Effect of norbixin-based poly(hydroxybutyrate) membranes on the tendon repair process after tenotomy in rats

Abstract Purpose: To determine the efficacy of norbixin-based poly(hydroxybutyrate) (PHB) membranes for Achilles tendon repair. Methods: Thirty rats were submitted to total tenotomy surgery of the right Achilles tendon and divided into two groups (control and membrane; n = 15 each), which were further subdivided into three subgroups (days 7, 14, and 21; n = 5 each). Samples were analyzed histologically. Results: Histological analysis showed a significant reduction in inflammatory infiltrates on days 7, 14 (p < 0.0001 for both), and 21 (p = 0.0004) in the membrane group compared to that in the control group. There was also a significant decrease in the number of fibroblasts in the control group on days 7, 14 (p < 0.0001), and 21 (p = 0.0032). Further, an increase in type I collagen deposition was observed in the membrane group compared to that in the control group on days 7 (p = 0.0133) and 14 (p = 0.0107). Conclusion: Treatment with norbixin-based PHB membranes reduces the inflammatory response, increases fibroblast proliferation, and improves collagen production in the tendon repair region, especially between days 7 and 14.

Histological features of restenosis associated with paclitaxel drug-coated balloon: implications for therapy.

PURPOSE: To investigate the cellular and extracellular changes induced by drug-coated balloons (DCB) in the treatment of superficial femoral artery (SFA) restenosis, and to compare histopathological features with those observed after plain old balloon angioplasty (POBA) from the same patients. METHODS AND RESULTS: Plaque samples for five patients with SFA restenosis (first-time) after POBA were collected using atherectomy and DCB. These samples constitute the POBA restenosis group. The same five patients developed recurrent restenosis (RR) after DCB, at the same intervention site. These SFA-RR lesions were again treated using atherectomy and POBA. These samples constitute the DCB restenosis group. DCB restenosis group plaques showed significant reduction in neointima, smooth muscle cells, fibroblast densities, and Ki67 index; and increase in caspase 3, features of apoptosis and type III collagen deposition in comparison to the POBA restenosis group. CONCLUSION: Plaque tissue from the DCB restenosis group show reductions in neointimal thickness, cellularity, and cellular proliferation, along with increased apoptosis, and Type III collagen content. These results suggest a different mechanistic pathway for DCB restenosis, in which neointimal proliferation is reduced but reparative fibrosis is increased. The treatment for SFA-RR after DCB may therefore benefit from different forms of therapy including scaffolding, rather than recurrent anti-proliferative therapy.

[Experimental study of platelet-rich plasma in treatment of Achilles tendinopathy in rabbits].

OBJECTIVE: To explore the effect of platelet-rich plasma (PRP) in treatment of Achilles tendinopathy in rabbits, and provide experimental evidence for the clinical application of PRP in treatment of Achilles tendinopathy. METHODS: Forty-eight adult New Zealand white rabbits, weighing 2.5-3.0 kg, male or female, were randomly divided into model group (group A), model control group (group B), model+treatment control group (group C), model+treatment group (group D), with 12 in each group. The rabbits were injected with type Ⅰ collagenase to prepare Achilles tendinopathy models in groups A, C, and D, and with an equal dose of normal saline in group B. The blood from the central artery of rabbit ear was taken to preprare PRP by secondary centrifugation in group D. The results of platelet counts showed that PRP platelets reached 3 to 5 times the whole blood. After the model was prepared, the rabbits in groups C and D were injected with physiological saline and autologous PRP at the molding site respectively, once a week, 0.8 mL each time for 4 weeks. At 1 week after PRP injection, the relative hardness (expressed as HRD%) of Achilles tendon was evaluated by ultrasound elastic quantitative imaging detection technique; the maximum breaking load of Achilles tendon was measured by universal electronic tensile testing machine; the contents of collagen type Ⅰ and Ⅲ were determined by ELISA; and the morphology of Achilles tendon collagen fibers was observed by HE and Masson stainings. RESULTS: All animals survived during the experiment. The results of ultrasound elastic quantitative imaging and mechanical tests showed that the HRD% and the maximum breaking load were significantly lower in group A than in group B ( P<0.05) and in group C than in group D ( P<0.05). The results of ELISA showed that the content of collagen type Ⅰ was significantly lower in group A than in group B ( P<0.05) and in group C than in group D ( P<0.05); the content of collagen type Ⅲ was significantly higher in group A than in group B ( P<0.05) and in group D than in group C ( P<0.05). HE and Masson stainings showed that the Achilles tendon collagen fibers were irregularly curled and the structure was severely damaged in group A; the fibers were parallel and ordered, and the structure was complete in group B; the fibers were irregularly curled and structurally disordered in group C; the fibers were slightly curled and the structure was relatively complete in group D. CONCLUSION: A rabbit model of Achilles tendinopathy can be reconstructed by type Ⅰ collagenase injection. PRP treatment can increase the Achilles tendon hardness and maximum breaking load, up-regulate the expression level of collagen type Ⅰ and Ⅲ, improve the structure of Achilles tendon collagen fiber, and promote the repair in rabbit Achilles tendinopathy model.

A comparative study of the epiligament of the medial collateral and the anterior cruciate ligament in the human knee. Immunohistochemical analysis of collagen type I and V and procollagen type III.

BACKGROUND: Recent reports in rat models have shown that fibroblasts in the epiligament, an enveloping tissue of the ligament, are not static cells and play an important role during the early ligament healing of isolated grade III injury of the collateral ligaments of the knee. Fibroblasts produce collagen types I, III and V and infiltrate within the ligament body via the endoligament. In addition, similarities have been reported between the structure of the epiligament of the medial collateral ligament and anterior cruciate ligament of the knee in rat and in human. In line with the ascribed role of the epiligament tissue and the synthesis of these collagens and their role in ligament healing, the aim of this study was to determine their presence in the normal epiligament of the aforementioned ligaments in humans, to compare their differential expression and to present a novel hypothesis about the failure of healing of the anterior cruciate ligament in contrast to the medial collateral ligament. MATERIALS AND METHODS: We used samples from the mid-substance of the medial collateral and the anterior cruciate ligament of the knee joint, acquired from 12 fresh knee joints. Routine histological analysis was performed through hematoxylin and eosin stain, Mallory's trichrome stain and Van Gieson's stain. The immunohistochemical analysis was conducted using monoclonal antibodies against collagen type I and V and procollagen type III. The number of cells in the epiligament, endoligament and the ligament tissue was assessed quantitatively through a computerized system for image analysis NIS-Elements Advanced Research and Statistica software. RESULTS: Our observations revealed certain differences in the morphology of the epiligament, as well as variations in the expression of the investigated molecules. Expression of collagen type I was mostly low-positive (1+) in the epiligament and positive (2+) in the ligament tissue of both ligaments. Expression of procollagen type III was mostly positive (2+) in the epiligament and ligament tissue of the medial collateral ligament, low-positive (1+) in the epiligament and negative (0) in ligament tissue of the anterior cruciate ligament. Expression of collagen type V was predominantly low-positive (1+) in the epiligament and negative (0) in the ligament tissue of both ligaments. The immunoreactivity for all three molecules was always higher in the epiligament of the medial collateral ligament than that of the anterior cruciate ligament. CONCLUSIONS: The results of our study illustrate for the first time that fibroblasts in the human epiligament are indeed responsible for the synthesis of the main types of collagen participating in the early ligament healing, thus corresponding to previous data of the medial collateral ligament healing in animal models. The differences between the epiligament of the investigated ligaments could add a novel explanation for the failed anterior cruciate ligament healing.

Collagen type III content of the long head of the biceps tendon as an indicator of glenohumeral arthritis.

Tendonosis is characterized by an increase in collagen type III relative to collagen type I, but the precise ratio of collagen type I to collagen type III in pathologic shoulder tendons has not been reported. A tendon continuously bathed in an OA synovial environment may exhibit histomorphologic differences as compared to those from shoulders with a preserved articular surface. The purpose of this study was to evaluate the biochemical and histological differences in the proximal portion of the long head of the biceps tendon (LHBT) from a non-arthritic versus an arthritic glenohumeral joint. Sixteen patients undergoing shoulder surgery were prospectively enrolled in the study. Group-1 consisted of patients with glenohumeral OA and Group-2 consisted of patients without OA. The LHBT was tenodesed and excised tendon was fixed, embedded, sectioned (5 µm), deparaffinized, and used for histology (H&E and Masson trichrome staining) and immunofluorescence analysis to determine levels of collagen III, MMP-1, MMP-9, TIMP-1, and TIMP-2. Compared to the patients without arthritis, group-1 exhibited significant inflammation with extracellular matrix disorganization and significantly higher (P < 0.05) collagen III, MMP-2, and MMP-9 levels. No considerable difference in collagen I was observed between the two groups. TIMP-1 and TIMP-2 were completely absent in both the groups. The level of collagen subtypes varied markedly between LHBT tendons from patients with and without OA. Increased collagen III in the LHBT is associated with glenohumeral arthritis. Measuring collagen type in the LHBT may serve as a useful metric in the diagnosis and treatment of musculoskeletal pathology.