Background:Arthrofibrosis is a frequent complication after total knee arthroplasty (TKA) and remains difficult to diagnose early due to the lack of reliable biomarkers. Excessive extracellular matrix (ECM) remodeling is driven by core signaling cascades, notably the Transforming Growth Factor-beta 1 (TGF-ß1) and Wnt/ß-catenin pathways. Xylosyltransferase-I (XT-I), a key enzyme regulating proteoglycan biosynthesis, has emerged as a critical downstream effector and potential indicator of early fibrotic activity. Methods:This narrative review summarizes clinical and experimental findings on XT-I in joint fibrosis, with emphasis on its role within the molecular network of key pro-fibrotic signaling and its diagnostic and translational potential in knee arthrofibrosis. Results:XT-I is consistently upregulated in fibrotic synovial fibroblasts and synovial fluid of arthrofibrotic knees, correlating with ECM remodeling and myofibroblast activation induced by both TGF-ß1and Wnt/ß-catenin signaling. XT-I demonstrates local rather than systemic diagnostic value and may serve as an early fibrosis indicator. Conclusion:XT-I holds promise as a synovial biomarker and potential therapeutic target in arthrofibrosis. Targeting XT-I, potentially in combination with core pathway inhibitors (e.g., Wnt/ß-catenin inhibitors), may offer a refined strategy for early diagnosis and postoperative management in TKA patients.

Arthrofibrosis of the knee joint is a severe complication following trauma and surgical procedures, which often results in long-term impairment of joint function. Early mobilization techniques and anesthesia are still employed without sufficient clarification of the underlying processes. While the early stages of arthrofibrosis can be successfully treated with conservative measures for pain reduction and wound healing, in the late stage tense collagenous scar tissue is frequently present that permanently limits joint mobility. In this stage an improvement of joint mobility has no chance of success without a surgical intervention. In surgical treatment a differentiation should be made between localized (mostly secondary) arthrofibrosis (e.g. cruciate ligament surgery) and generalized arthrofibrosis (in the majority of cases primarily after total knee arthroplasty) and the treatment planned accordingly. Comorbid pathological alterations (transplant position, instability of the total knee endoprosthesis, implant attrition, low-grade infection, patellofemoral instability or maltracking, patella baja) must be taken into consideration in the treatment. A multimodal accompanying treatment including physiotherapy, pain therapy and psychosomatics is necessary to ensure successful treatment.

Comparable data of functional outcomes of anterior cruciate ligament reconstruction using either hamstring- or quadriceps tendon grafts is controversial. This prospective, randomized controlled trial aims to provide data comparing both grafts regarding the functional outcome. A two centre trial involving symptomatic patients 18 years of age or older with an anterior cruciate ligament tear was conducted. We randomly assigned 27 patients to quadruple hamstring tendon reconstruction and 24 to quadriceps tendon reconstruction. The patients were evaluated preoperatively, at 3, 6, 12 and 24 months post-surgery. The primary outcome parameter was the side-to-side knee laxity measured with an arthrometer. Secondary outcomes included results in the International Knee Documentation Committee (IKDC) and Lysholm Scores and isokinetic testing of strength in knee extension and flexion. Forty-four patients (86%) completed the 2-year follow-up. There was significantly improved knee stability at all time intervals with no difference between the two study groups. The manual side-to-side displacement improved by 4.7 ± 3.0 mm in patients with hamstring tendon reconstruction and 5.5 ± 2.9 mm in patients with quadriceps tendon reconstruction. In addition, muscle strength and outcome scores (IKDC and Lysholm Score) did not show any differences between the hamstring tendon group and the quadriceps tendon group. Patients in the hamstring tendon group returned to their pre-injury activity level after 95.2 ± 45.5 days while patients in the quadriceps tendon group needed 82.1 ± 45.6 days. Quadriceps and hamstring tendon autografts yield comparably good results in primary anterior cruciate ligament reconstruction.

Osteoarthritis and rheumatoid arthritis are the most ubiquitous joint disorders which cause tremendous loss of life quality and impose an economic burden on society. At present, the treatment options for these two diseases comprise non-operative and surgical treatments, amongst those total knee arthroplasties (TKA). Various studies have recognized smoking as a significant risk factor for postoperative complications. Therefore, the purpose of this study was to examine the impact of smoking on the incidence and postoperative complications after a total knee arthroplasty by a systematic review and meta-analysis. The research was performed using PUBMED, Cochrane Library and EMBASE, extracting data from thirteen suitable studies and incorporating 2,109,482 patients. Cohort studies evaluating the impact of smoking on TKA with sufficient data were included for the study, and cohort studies without a proper control group and complete data were excluded. A fixed-effects or random-effects model was used to measure the pooled risk ratio (RR) or hazard ratio (HR) with 95% confidence interval (CI). Compared to non-smokers, smokers had a significantly lower incidence of TKA (p<0.01). However, smokers had a higher incidence of total complications (p=0.01), surgical complications (p<0.01), pneumonia (p<0.01) and revision surgery (p=0.01). No significant difference in the risk of blood transfusion (p=0.42), deep vein thrombosis (p=0.31), pulmonary embolism (p=0.34), urinary tract infection (p=0.46) or mortality (p=0.39) was found between smokers and non-smokers. In conclusion, the study indicated that tobacco has two diametrically opposite effects on TKA patients: 1. Tobacco increases the incidence of surgical complications, pneumonia and revision after TKA; 2. It decreases the overall risk of being a candidate for TKA.

Operative Eingriffe für einen Gelenk- oder Kreuzbandersatz sind heute Routine. Dennoch entwickeln manche Patienten im Nachhinein eine Arthrofibrose. Sind die konservativen Maßnahmen ausgeschöpft, kann ein erneuter operativer Eingriff helfen.

In this current study, a novel multilayer porous composite scaffold was fabricated with chitosan (CS), silk fibrin (SF) and nano-hydroxyapatite (n-HA). Scanning electron microscope was utilized to detect the characteristics of the composed scaffold. Rat bone marrow stromal cells (rBMSC) were loaded onto the CS/SF/n-HA scaffold and cultured in a bioreactor under an on-off dynamic compression (10% compressive strain, 0.5 Hz, [2 h action + 4 h pause]/cycle, 4 cycles/day). Metabolism of the loaded rBMSC was assessed through CCK-8 test. Qualitative polymerase chain reaction and western blot were applied to assess the chondrogenic differentiation of the seeded cells. Compressive modulus of the cell/scaffold constructs was analyzed. Additionally, a pig model was employed to evaluate the effect of the tissue-engineered cartilage on repairing of cartilage defect. Results showed that the four layers within the scaffold were tightly connected without gaps between porous interfaces of the layers. Scaffold porosity was 92.20% ± 1.30%. The cyclic compression upregulated chondrogenesis markers (Aggrecan, Sox-9, and collagen II). Increased compressive modulus of the cell/scaffold complex was detected after dynamic compression. The pig bone marrow stromal cells/scaffold complex exposed to cyclic compression presented most favorable reparative effect on the mini pig femoral condyle cartilage defects. Our study suggested that the on-off dynamic compression might be a promising approach to fabricate tissue-engineered cartilage in vitro. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1294-1302, 2019.

Background: The goal of this study is to investigate the biomechanical and histological properties of in vivo heterotopically prefabricated cruciate ligament replacement grafts with and without mechanical stimulation. The clinical goal is to heterotopically prefabricate a bone-tendon-bone graft for anterior cruciate ligament reconstruction, which allows rapid ingrowth and early full weight bearing. Methods: In a sheep model, eight quadriceps tendon grafts were harvested and introduced into culture chambers at their proximal and distal ends. In group S, four tendon-chamber constructs were mechanically stimulated by direct attachment to the quadriceps tendon and patella. In group NS, the same constructs were cultured without proximal attachment. All sheep were sacrificed six weeks postoperatively and the constructs were examined biomechanically and histologically. The healthy contralateral ACL and quadriceps tendon were used as controls. Results: Macroscopically, no obvious ossification could be observed at the ends of the tendon chamber constructs six weeks postoperatively. Histologically, the tendon tissue from the mechanically stimulated constructs revealed higher counts of cells and capillaries. However, there was less regular cell distribution and collagen fiber orientation compared to the control group. In addition, osteoblasts and osteogenesis were observed in the prefabricated constructs both with and without mechanical stimulation. Biomechanically, there were no significant differences in stiffness, elongation and ultimate failure load between the groups. Conclusion: In vivo heterotopic culture of prefabricated tendon grafts may have the potential to stimulate osteoblasts and induce osteogenesis. Future studies with longer follow-up and modifications of the surgical technique and culture conditions are desirable. (C) 2018 Published by Elsevier B.V.

Objectives The aims of this study were to determine whether the administration of anti-inflammatory and antifibrotic agents affect the proliferation, viability, and expression of markers involved in the fibrotic development of the fibroblasts obtained from arthrofibrotic tissue in vitro, and to evaluate the effect of the agents on arthrofibrosis prevention in vivo. Methods Dexamethasone, diclofenac, and decorin, in different concentrations, were employed to treat fibroblasts from arthrofibrotic tissue (AFib). Cell proliferation was measured by DNA quantitation, and viability was analyzed by Live/Dead staining. The levels of procollagen type I N-terminal propeptide (PINP) and procollagen type III N-terminal propeptide (PIIINP) were evaluated with enzyme-linked immunosorbent assay (ELISA) kits. In addition, the expressions of fibrotic markers were detected by real-time polymerase chain reaction (PCR). Fibroblasts isolated from healthy tissue (Fib) served as control. Further, a rabbit model of joint contracture was used to evaluate the antifibrotic effect of the three different agents. Results Dexamethasone maintained the viability and promoted the proliferation of AFib. Diclofenac decreased the viability and inhibited the cell proliferation during the first week of cultivation. However, decorin inhibited AFib proliferation and downregulated the expressions of fibrotic markers. Additionally, decorin could improve the flexion contracture angle and inhibit the deposition of interstitial matrix components in the rabbit joint model. Conclusion Decorin decreased the expression of myofibroblast markers in AFib, inhibited the proliferation of AFib, and prevented the initial procedure of arthrofibrosis in vivo, suggesting that decorin could be a promising treatment to inhibit the development of arthrofibrosis.

Die Arthrofibrose nach der Implantation einer Knie-Totalendoprothese gehört mit 1–13 % zu den häufigsten Komplikationen nach diesem Eingriff und ist somit für die relativ hohe Unzufriedenheitsrate der mit einer Knie-Endoprothese versorgten Patienten mitverantwortlich. Da bisher keine Differenzierung zwischen Arthrofibrose und Adhäsion („Verklebung“) vorgenommen wird, werden beide Pathologien nach dem „Verklebungsmodell“ mechanisch behandelt. Bei der Arthrofibrose führt dies meist zu einem schlechten Ergebnis. Das hier vorgestellte zelluläre, Zytokin-basierte Pathogenese- und hypothetische Stadienmodell der Arthrofibrose könnte die bisherige Behandlung dieser schwerwiegenden Komplikation verändern.

Traumatic knee dislocation is a rare but potentially limb-threatening injury. Thus proper initial diagnosis and treatment up to final ligament reconstruction are extremely important and a precondition to successful outcomes. Reports suggest that evidence-based systematic approaches lead to better results. Because of the complexity of this injury and the inhomogeneity of related literature, there are still various controversies and knowledge gaps regarding decision-making and step-sequencing in the treatment of acute multi-ligament knee injuries and knee dislocations. The use of ankle-brachial index, routine or selective angiography, braces, joint-spanning or dynamic external fixation, and the necessity of initial ligament re-fixation during acute surgery constitutes current topics of a scholarly debate. The aim of this article was to provide a comprehensive literature review bringing light into some important aspects about the initial treatment of knee dislocation (vascular injury, neural injury, immobilization techniques) and finally develop an accurate data-based universal algorithm, enabling attending physicians to become more acquainted with the management of acute knee dislocation.

Hydraulic pressure has recently been introduced as an effective stimulation in the field of tissue engineering. In this study, a polymer scaffold consisting of polyurethane (PU)-based 1, 4-butanediisocyanate was fabricated. A self-designed bioreactor was employed to produce perfusion and hydrodynamic pressure stimulations. The viability, proliferation and osteogenic differentiation of the rat bone mesenchymal stromal cell (rBMSC) growing in the polymer scaffold were investigated after hydrodynamic pressure stimulation. Additionally, the mechanical properties of the cell-laden constructs were also evaluated. Our findings suggested that the perfusion rate (10 mL/min) and low hydrodynamic pressure stimulation (60 mmHg, 0.5 Hz) maintained the viability of rBMSC during 2 weeks cultivation. The cell proliferation was promoted by 60 mmHg stimulation in the first week. The synthesis of alkaline phosphates and osteocalcin was enhanced after 2 weeks stimulation. Meanwhile, the equilibrium modulus of scaffold was increased by 1.85-fold using 60 mmHg hydrodynamic pressure stimulation. Additionally, type I and III procollagen produced by rBMSC was increased 4.92- and 3.02-fold, respectively. However, no encouraging results were detected in 120 mmHg hydrodynamic pressure group. Our study suggests that the 60 mmHg hydrodynamic pressure is a promising approach to enhance the functional properties of the rBMSC-laden PU-based bone scaffold. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3445-3455, 2017.

Background: Adipose tissue is a promising source of mesenchymal stromal cells (MSCs) for the treatment of tendon disease. The goal of this study was to assess the effect of a single intralesional implantation of adipose tissue-derived mesenchymal stromal cells (AT-MSCs) on artificial lesions in equine superficial digital flexor tendons (SDFTs).Methods: During this randomized, controlled, blinded experimental study, either autologous cultured AT-MSCs suspended in autologous inactivated serum (AT-MSC-serum) or autologous inactivated serum (serum) were injected intralesionally 2 weeks after surgical creation of centrally located SDFT lesions in both forelimbs of nine horses. Healing was assessed clinically and with ultrasound (standard B-mode and ultrasound tissue characterization) at regular intervals over 24 weeks. After euthanasia of the horses the SDFTs were examined histologically, biochemically and by means of biomechanical testing.Results: AT-MSC implantation did not substantially influence clinical and ultrasonographic parameters. Histology, biochemical and biomechanical characteristics of the repair tissue did not differ significantly between treatment modalities after 24 weeks. Compared with macroscopically normal tendon tissue, the content of the mature collagen crosslink hydroxylysylpyridinoline did not differ after AT-MSC-serum treatment (p = 0.074) while it was significantly lower (p = 0.027) in lesions treated with serum alone. Stress at failure (p = 0.048) and the modulus of elasticity (p = 0. 001) were significantly lower after AT-MSC-serum treatment than in normal tendon tissue.Conclusions: The effect of a single intralesional injection of cultured AT-MSCs suspended in autologous inactivated serum was not superior to treatment of surgically created SDFT lesions with autologous inactivated serum alone in a surgical model of tendinopathy over an observation period of 22 weeks. AT-MSC treatment might have a positive influence on collagen crosslinking of remodelling scar tissue. Controlled long-term studies including naturally occurring tendinopathies are necessary to verify the effects of AT-MSCs on tendon disease.

The aim of the present investigation was to compare the effects of cyclic compression, perfusion, dexamethasone (DEX) and bone morphogenetic protein-7 (BMP-7) on the proliferation and differentiation of human bone marrow stromal cells (hBMSCs) in polyurethane scaffolds in a perfusion bioreactor. Polyurethane scaffolds seeded with hBMSCs were cultured under six different conditions, as follows: 10% Cyclic compression at 0.5 and 5 Hz; 10 ml/min perfusion; 100 nM DEX; 100 ng/ml BMP-7; and 1 ml/min perfusion without mechanical and biochemical stimulation (control). On days 7 and 14, samples were tested for the following data: Cell proliferation; mRNA expression of Runx2, COL1A1 and osteocalcin; osteocalcin content; calcium deposition; and the equilibrium modulus of the tissue specimen. The results indicated that BMP-7 and 10 ml/min perfusion promoted cell proliferation, which was inhibited by 5 Hz cyclic compression and DEX. On day 7, the 5 Hz cyclic compression inhibited Runx2 expression, whereas the 0.5 Hz cyclic compression and BMP-7 upregulated the COL1A1 mRNA levels on day 7 and enhanced the osteocalcin expression on day 14. The DEX-treated hBMSCs exhibited downregulated osteocalcin expression. After 14 days, the BMP-7 group exhibited the highest calcium deposition, followed by the 0.5 Hz cyclic compression and the DEX groups. The equilibrium modulus of the engineered constructs significantly increased in the BMP-7, 0.5 Hz cyclic compression and DEX groups. In conclusion, the present results suggest that BMP-7 and perfusion enhance cell proliferation, whereas high frequency cyclic compression inhibits the proliferation and osteogenic differentiation of hBMSCs. Low frequency cyclic compression is more effective than DEX, but less effective compared with BMP-7 on the osteogenic differentiation of hBMSCs seeded on polyurethane scaffolds.

Background Press-fit fixation of patellar tendon–bone anterior cruciate ligament autografts is an interesting technique because no hardware is necessary. For hamstring tendon grafts, no biomechanical data exist of a press-fit procedure. Hypothesis Press-fit femoral fixation of hamstring tendons is mechanically equivalent to press-fit patellar tendon–bone fixation. Study Design Controlled laboratory study. Methods Patellar and hamstring tendons of 30 human cadavers (age, 53.8 ± 18.0 years) were used. An outside-in press-fit fixation with a knot in the semitendinosus and gracilis tendons and an inside-out and outside-in fixation with the tendons wrapped around a bone block were compared with patellar tendon–bone press-fit fixation in 30 ovine femora. Constructs were cyclically strained and then loaded until failure. Maximum load to failure, stiffness, and elongation during failure testing and cyclical loading were investigated. Results The maximum load to failure was 561 ± 309 N for the patellar tendon, 599 ± 234 N for the semitendinosus/gracilis tendons knot construct, 678 ± 231 for the semitendinosus/gracilis tendons bone construct inserted outside in, and 339 ± 236 for the semitendinosus/gracilis tendons bone construct inserted inside out (inferior to the others; analysis of variance, Dunn test, P < .01). Stiffness of the constructs averaged 134 ± 32 N/mm for the patellar tendon, 124 ± 21 N/mm for the knot construct, 118 ± 27 N/mm for the outside-in fixation, and 117 ± 23 N/mm for inside-out fixation. Elongation during initial cyclical loading was 0.7 ± 0.6 mm for the patellar tendon, 1.6 ± 0.5 mm for the knot construct, 1.9 ± 1.2 mm for the outside-in fixation, and 1.9 ± 0.9 mm for the inside-out fixation (significantly larger for all semitendinosus/gracilis tendon techniques, P < .05). Conclusions Failure loads for the semitendinosus/gracilis tendons bone construct inserted outside in and the semitendinosus/gracilis tendons knot construct were within the confidence interval of the patellar tendon press-fit fixation. All semitendinosus/gracilis tendon graft techniques exhibited larger elongation during initial cyclical loading than the patellar tendon graft. There was no difference in stiffness between all techniques. Clinical Relevance Two of the 3 hamstring press-fit fixation techniques showed loads to failure similar to the patellar tendon fixation. Preconditioning of the constructs is critical. These results must be interpreted with care because of high standard deviations.