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Background: Cartilage grafts are commonly used in nasal surgery for structural and/or esthetic purposes. The viability of cartilage grafts has been investigated in many forms since the use of cartilage grafts in surgical procedures., Objectives: The objective of this study was to investigate the viability of minced cartilage grafts and whether there is a difference between grafts wrapped in Surgicel(®) Original and Surgicel Fibrillar., Methods: A total of ten New Zealand rabbits were used for the study. Cartilage grafts were harvested from one side ear. Four groups were formed. Group 1: minced cartilage graft wrapped in Surgicel Fibrillar; Group 2: minced cartilage graft wrapped in Surgicel Original; Group 3: bare minced cartilage graft; and Group 4: bare diced cartilage graft. Four small subcutaneous pockets were made in the backs of the rabbits, and the grafts were placed in these pockets. All of the rabbits were sacrificed at the end of 3 months, and the samples were collected. The sections were stained with hematoxylin and eosin (H&E), toluidin blue, safranin-O, masson trichrome, and glial fibrillary acidic protein immunohistochemical. All specimens were assessed histopathologically under a light microscope., Results: There was no statistically significant difference between the Surgicel Fibrillar and Surgicel Original groups with respect to any of the parameters. Bone formation, calcification, inflammation, fibrosis, and basophilia were similar in all groups, with no significant difference among them. In the Surgicel Fibrillar and Surgicel Original groups, a heavy chondrocyte nucleus loss accompanied by a minimal peripheral proliferation was observed., Conclusions: The viability of bare minced cartilage grafts was found to be similar to that of bare diced cartilage in this study. Minced cartilage grafts can be used in the correction of minor dorsal defects and irregularities in persons with thin nasal skins, especially in primary and revision rhinoplasty. Although there is no statistically significant difference between the Surgicel Fibrillary and Surgicel Original groups, we think that, if it is necessary to use oxidized regenerated cellulose, it should be in the fibrillar form., No Level Assigned: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .

Background: Recent studies suggest that fluoroquinolone antibiotics predispose tendons to tendinopathy and/or rupture. However, no investigations on the reparative capacity of tendons exposed to fluoroquinolones have been conducted., Hypothesis: Fluoroquinolone-treated animals will have inferior biochemical, histological, and biomechanical properties at the healing tendon-bone enthesis compared with controls., Study Design: Controlled laboratory study., Methods: Ninety-two rats underwent rotator cuff repair and were randomly assigned to 1 of 4 groups: (1) preoperative (Preop), whereby animals received fleroxacin for 1 week preoperatively; (2) pre- and postoperative (Pre/Postop), whereby animals received fleroxacin for 1 week preoperatively and for 2 weeks postoperatively; (3) postoperative (Postop), whereby animals received fleroxacin for 2 weeks postoperatively; and (4) control, whereby animals received vehicle for 1 week preoperatively and for 2 weeks postoperatively. Rats were euthanized at 2 weeks postoperatively for biochemical, histological, and biomechanical analysis. All data were expressed as mean ± standard error of the mean (SEM). Statistical comparisons were performed using either 1-way or 2-way ANOVA, with P < .05 considered significant., Results: Reverse transcriptase quantitative polymerase chain reaction (RTqPCR) analysis revealed a 30-fold increase in expression of matrix metalloproteinase (MMP)-3, a 7-fold increase in MMP-13, and a 4-fold increase in tissue inhibitor of metalloproteinases (TIMP)-1 in the Pre/Postop group compared with the other groups. The appearance of the healing enthesis in all treated animals was qualitatively different than that in controls. The tendons were friable and atrophic. All 3 treated groups showed significantly less fibrocartilage and poorly organized collagen at the healing enthesis compared with control animals. There was a significant difference in the mode of failure, with treated animals demonstrating an intrasubstance failure of the supraspinatus tendon during testing. In contrast, only 1 of 10 control samples failed within the tendon substance. The healing enthesis of the Pre/Postop group displayed significantly reduced ultimate load to failure compared with the Preop, Postop, and control groups. There was no significant difference in load to failure in the Preop group compared with the Postop group. Pre/Postop animals demonstrated significantly reduced cross-sectional area compared with the Postop and control groups. There was also a significant reduction in area between the Preop and control groups., Conclusion: In this preliminary study, fluoroquinolone treatment negatively influenced tendon healing., Clinical Relevance: These findings indicate that there was an active but inadequate repair response that has potential clinical implications for patients who are exposed to fluoroquinolones before tendon repair surgery., (© 2014 The Author(s).)

Background: The repair and restoration of function after chronic rotator cuff tears are often complicated by muscle atrophy, fibrosis, and fatty degeneration of the diseased muscle. The inflammatory response has been implicated in the development of fatty degeneration after cuff injuries. Licofelone is a novel anti-inflammatory drug that inhibits 5-lipoxygenase (5-LOX), as well as cyclooxygenase (COX)-1 and COX-2 enzymes, which play important roles in inducing inflammation after injuries. While previous studies have demonstrated that nonsteroidal anti-inflammatory drugs and selective inhibitors of COX-2 (coxibs) may prevent the proper healing of muscles and tendons, studies about bone and cartilage have demonstrated that drugs that inhibit 5-LOX concurrently with COX-1 and COX-2 may enhance tissue regeneration., Hypothesis: After the repair of a chronic rotator cuff tear in rats, licofelone would increase the load to failure of repaired tendons and increase the force production of muscle fibers., Study Design: Controlled laboratory study., Methods: Rats underwent supraspinatus release followed by repair 28 days later. After repair, rats began a treatment regimen of either licofelone or a vehicle for 14 days, at which time animals were euthanized. Supraspinatus muscles and tendons were then subjected to contractile, mechanical, histological, and biochemical analyses., Results: Compared with controls, licofelone-treated rats had a grossly apparent decrease in inflammation and increased fibrocartilage formation at the enthesis, along with a 62% increase in the maximum load to failure and a 51% increase in peak stress to failure. Licofelone resulted in a marked reduction in fibrosis and lipid content in supraspinatus muscles as well as reduced expression of several genes involved in fatty infiltration. Despite the decline in fibrosis and fat accumulation, muscle fiber specific force production was reduced by 23%., Conclusion: The postoperative treatment of cuff repair with licofelone may reduce fatty degeneration and enhance the development of a stable bone-tendon interface, although decreases in muscle fiber specific force production were observed, and force production in fact declined., Clinical Relevance: This study demonstrates that the inhibition of 5-LOX, COX-1, and COX-2 modulates the healing process of repaired rotator cuff tendons. Although further studies are necessary, the treatment of patients with licofelone after cuff repair may improve the development of a stable enthesis and enhance postoperative outcomes., (© 2014 The Author(s).)

Objective: To analyse the effect of low intensity pulsed ultrasound stimulation (LIPUS) on accelerating the fibrocartilage layer repair of patella-patellar tendon junction., Methods: A total of 60 mature female New Zealand white rabbits undergoing standard partial patellectomy were divided into 2 groups randomly. The control group was given comfort treatment and the treatment group was given LIPUS treatment starting from day 3 to the end of week 6 postoperatively. The scheduled time points of animal euthanization would be at week 6, week 12 and week 18 postoperatively. The patella-patellar tendon (PPT) complex would be harvested and cut into sections after decalcification for H&E staining, Safranine o/fast green staining. The thickness and gray value of fibrocartilage layer were analyzed by SANO Microscope Partner image analyzer., Results: At week 6, week 12 and week 18 postoperatively, the fibrocartilage layer in the treatment group was significantly thicker than that in the control group (P<0.01), and the gray value of fibrocartilage layer was significantly smaller than that in the control group (P<0.01)., Conclusion: LIPUS helps to accelerate the fibrocartilage layer repair of patella-patellar tendon junction in rabbit models.

Purpose: The purpose of this study was to histologically examine the human healing response of arthroscopically repaired acetabular labrum tears., Methods: Biopsy specimens were retrieved from 6 patients during total hip arthroplasty after clinical failure of the index arthroscopic procedure. All patients were diagnosed as having femoroacetabular impingement with a concomitant labral tear. In all cases severe chondral damage was observed during arthroscopy (Beck grades 3 to 4). Despite successful technical repair of the labral tear, chondral damage in these patients was so advanced that the clinical progress after the procedure was unsatisfactory and arthroplasty of the joint was required. Biopsy specimens of the repaired acetabular labra were harvested during the arthroplasty surgery and processed for standard histologic evaluation., Results: Macroscopically and histologically, all repaired labra kept their triangular shape more or less and appeared to have healed. All harvested biopsy specimens displayed a typical fibrocartilaginous appearance with limited vascular supply. Calcifications were present in only 1 biopsy specimen. In 3 cases neovascularization of the labral tissue was noticed in the proximity of the sutures. In the superficial and deep parts of the labral body, small clefts were observed in all cases., Conclusions: In this study the histologic aspects of arthroscopically repaired human labral tears were addressed. It was shown that human labral tears show healing potential after surgical repair. The surfaces of the labral tissues were intact, and neither remnants of the tear nor the presence of fibrovascular scar tissue was observed. However, some small clefts in the superior and deep parts of the repaired structures were noticed in all cases., Level of Evidence: Level IV, therapeutic case series., (Copyright © 2012 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Purpose: To examine the entire repair tissue resulting from marrow-stimulation techniques in patients with early osteoarthritis., Methods: The repair tissue and adjacent articular cartilage after failed marrow-stimulation techniques (microfracture and Pridie drilling) of 5 patients (47-65 years old) with cartilage defects and radiographic early osteoarthritis (Kellgren-Lawrence grading 1 and 2) was removed during total joint arthroplasty (mean time until analysis: 8.8 months), analysed by histology, polarized light microscopy, immunohistochemistry, biochemistry and by histological score systems., Results: Macroscopic cartilage repair assessment revealed ICRS grades of II (nearly normal) and III (abnormal). Cartilage defects were mostly completely filled with a fibrocartilaginous tissue that had small and large fissures. Cartilage-specific stains of the repair tissue were more intense than the surrounding native cartilage but reduced compared with normal articular cartilage. The subchondral bone was incompletely restored. A new tidemark was absent. The repair tissue always showed positive immunoreactivity for types II and X collagen, and was sometimes positive for type I collagen. Proteoglycan contents of the repair tissue were generally higher than of the surrounding cartilage. The repair tissue was always more cellular than the adjacent articular cartilage. Histological scoring of the repair tissue revealed a mean Sellers score of 17.6 ± 3.0 and an ICRS grading of 7-9., Conclusion: Failed marrow stimulation of articular cartilage defects in patients with early osteoarthritis is characterized by fibrocartilaginous repair. The balance of cell number to extracellular matrix is shifted towards an increased cell number in this tissue. Articular cartilage repair did not reach the quality of normal hyaline articular cartilage., Level of Evidence: IV.

Purpose: Ligaments are frequently damaged in sports activities and trauma, and severe ligament injury can lead to joint instability and osteoarthritis. In this study, we aimed to regenerate the medial collateral ligament (MCL) using an absorbable stent-shaped poly-L-lactic acid (PLLA) scaffold in a rabbit model to examine the biocompatibility and mechanical properties., Methods: Twenty-three Japanese white rabbits were used in this study. MCL defects were surgically created in the knee joints and then reconstructed using stent-shaped PLLA scaffolds. As controls, flexor digitorum longus (FDL) tendons were implanted into the contralateral knees. Seven rabbits were sacrificed at three time points, conducted four, eight and 16 weeks after the operation. The regenerated tissues were histologically evaluated using fibre alignment scoring, morphology of fibroblast scoring and immunohistochemical analysis of types I and III collagen. The regenerated tissues were also biomechanically evaluated by measuring the ultimate failure load and stiffness., Results: At four weeks post-operation, spindle-shaped cells were observed on the inside of the scaffolds. At eight weeks, maturation of the regenerated tissues and collagen fibre alignment parallel to the ligaments was observed. At 16 weeks, the fibre alignment had become denser. The fibre alignment and morphology of fibroblast scores significantly increased in a time-dependent manner. Expression of type I collagen was more strongly observed in the scaffold group at eight and 16 weeks post-operation than at four weeks. Type III collagen was also observed at four, eight and 16 weeks post-operation. A thin layer of fibrocartilage was observed at the ligament-bone junction at eight and 16 weeks. The ultimate failure load of the scaffold group was 46.7 ± 20.7 N, 66.5 ± 11.0 N and 74.3 ± 11.5 N at four, eight and 16 weeks post-operation, respectively. There was no statistical difference between the normal MCL and the scaffold group at 16 weeks post-operation., Conclusions: The stent-shaped PLLA scaffold allowed for MCL regeneration with type I collagen expression and fibrocartilage formation and resulted in sufficient mechanical function.

Healing at the osteotendinous junction (OTJ) is challenging in orthopedic surgery. The present study aimed to test extracorporeal shockwave (ESW) in treatment of a delayed OTJ healing. Twenty-eight rabbits were used for establishing a delayed healing (DH) model at patella-patellar-tendon (PPT) complex after partial patellectomy for 4 weeks and then were divided into DH and ESW groups. In the ESW group, a single ESW treatment was given at postoperative week 6 to the PPT healing complex. The samples were harvested at week 8 and 12 for radiographic and histological evaluations with seven samples for each group at each time point. Micro-CT results showed that new bone volume was 1.18 +/- 0.61 mm(3) in the ESW group with no measurable new bone in the DH group at postoperative week 8. Scar tissue formed at the OTJ healing interface of the DH group, whereas ESW triggered high expression of VEGF in hypertrophic chondrocytes at week 8 and regeneration of the fibrocartilage zone at week 12 postoperatively. The accelerated osteogenesis could be explained by acceleration of endochondral ossification. In conclusion, ESW was able to induce osteogenesis at OTJ with delayed healing with enhanced endochondral ossification process and regeneration of fibrocartilage zone. These findings formed a scientific basis to potential clinical application of ESW for treatment of delayed OTJ healing.

The fibrocartilage transition zone in the direct bone-tendon junction reduces stress concentration and protects the junction from failure. Unfortunately, bone-tendon junctions often heal without fibrocartilage transition zone regeneration. We hypothesized articular cartilage grafts could increase fibrocartilage transition zone regeneration. Using a goat partial patellectomy repair model, autologous articular cartilage was harvested from the excised distal third patella and interposed between the residual proximal two-thirds bone fragment and tendon during repair in 36 knees. We evaluated fibrocartilage transition zone regeneration, bone formation, and mechanical strength after repair at 6, 12, and 24 weeks and compared them with direct repair. Autologous articular cartilage interposition resulted in more fibrocartilage transition zone regeneration (69.10% +/- 14.11% [mean +/- standard deviation] versus 8.67% +/- 7.01% at 24 weeks) than direct repair at all times. There was no difference in the amount of bone formation and mechanical strength achieved. Autologous articular cartilage interposition increases fibrocartilage transition zone regeneration in bone-tendon junction healing, but additional research is required to ascertain the mechanism of stimulation and to establish the clinical applicability.

The anatomical structure at bone-tendon and bone-ligament interfaces is called the enthesis. Histologically, the enthesis is characterized by a transitional series of tissue layers from the end of the tendon to bone, including tendon, fibrocartilage, calcified fibrocartilage, and bone. This arrangement yields stronger direct connection of the soft tissues to bone. In surgical repair, the enthesis has proven difficult to reproduce, and the success of ligament-bone bonding has depended on the fibrous attachment that forms after any ligament reconstructions. In this study, we attempted to generate a direct-insertion enthesis in two stages. First, recombinant human bone morphogenetic protein-2 (rhBMP-2) was injected into the flexor digitorum communis tendon in the rabbit hind limb to induce ectopic ossicle formation. In a second step, the resultant tendon/ossicle complex was then surgically transferred onto the surface of the rabbit tibia to generate a stable tendon-bone junction. One month following surgery, histomorphological examination confirmed direct insertion of tendon-bone structures in the proximal tibia of the rabbit. Ultimate failure loads of the BMP-2-generated tendon-bone junction were significantly higher than in the control group (p < 0.01). These findings suggest that it is possible to successfully regenerate a direct tendon-to-bone enthesis. Use of this approach may enable successful reconstruction of joints rendered unstable after ligamentous rupture or laxity after anterior cruciate ligament injury., ((c) 2007 Orthopaedic Research Society.)

The purpose of this study was to find out whether supraspinatus repair delayed by up to12 weeks affects the formation of a new enthesis when compared to an immediate repair. In 67 rabbits, the supraspinatus fibrocartilaginous enthesis of one shoulder was resected. The tendon was attached to the greater tuberosity either immediately, after a 6-week, or after a 12-week delay. Five histologic variables were used to assess enthesis formation: number of non-chondrocytes, number of chondrocytes, alignment of chondrocytes in rows, area of metachromasia on toluidine blue (TB)-stained sections indicating proteoglycan content, and area of diffracted polarized light indicating spatial alignment of collagen fibers. For every variable, progressive enthesis formation was observed. Again, for every variable and at every time point studied, no statistically significant difference was observed between tendons repaired immediately, after 6, or after 12 weeks (all p>0.05). Supraspinatus tendon repairs delayed by 6 and 12 weeks constituted an enthesis which proceeded identically to one immediately repaired. Formation of a fibrocartilaginous enthesis depended on the elapsed time after repair and not on the duration between detachment and repair. Despite stated limitations, these results support both a trial of conservative treatment after a rotator cuff tear and a positive outcome of rotator cuff repair even if delayed by up to 12 weeks., ((c) 2005 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.)