Objectives. The role of mechanical stress and transforming growth factor beta 1 (TGF-β1) is important in the initiation and progression of osteoarthritis (OA). However, the underlying molecular mechanisms are not clearly known. Methods. In this study, TGF-β1 from osteoclasts and knee joints were analyzed using a co-cultured cell model and an OA rat model, respectively. Five patients with a femoral neck fracture (four female and one male, mean 73.4 years (68 to 79)) were recruited between January 2015 and December 2015. Results showed that TGF-β1 was significantly upregulated in osteoclasts by cyclic loading in a time- and dose-dependent mode. The osteoclasts were subjected to cyclic loading before being co-cultured with chondrocytes for 24 hours. Results. A significant decrease in the survival rate of co-cultured chondrocytes was found. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) assay demonstrated that mechanical stress-induced apoptosis occurred significantly in co-cultured chondrocytes but administration of the TGF-β1 receptor inhibitor, SB-505124, can significantly reverse these effects. Abdominal administration of SB-505124 can attenuate markedly articular cartilage degradation in OA rats. Conclusion. Mechanical stress-induced overexpression of TGF-β1 from osteoclasts is responsible for chondrocyte apoptosis and cartilage degeneration in OA. Administration of a TGF-β1 inhibitor can inhibit articular cartilage degradation. Cite this article: R-K. Zhang, G-W. Li, C. Zeng, C-X. Lin, L-S. Huang, G-X. Huang, C. Zhao, S-Y. Feng, H. Fang. Mechanical stress contributes to osteoarthritis development through the activation of transforming growth factor beta 1 (TGF-β1). Bone Joint Res 2018;7:587–594. DOI: 10.1302/2046-3758.711.BJR-2018-0057.R1

Wear is an important factor in the long term success of total knee arthroplasty. Therefore, wear testing methods and machines become a standard in research and implant development. These methods are based on two simulation concepts which are defined in standards ISO 14243-1 and 14243-3. The difference in both concepts is the control mode. One is force controlled while the other has a displacement controlled concept. The aim of this study was to compare the mechanical stresses within the different ISO concepts. Furthermore the force controlled ISO was updated in the year 2009 and should be compared with the older which was developed in 2001. A finite element model based on the different ISO standards was developed. A validation calculated with kinematic profile data of the same implant (Aesculap, Columbus CR) in an experimental wear test setup (Endolap GmbH) was done. Based on this model all three different ISO standards were calculated and analysed. Validation results showed Pearson correlation for anterior posterior movement of 0.3 and for internal external rotation 0.9. Two main pressure maximums were present in ISO 14243-1:2001 (force controlled) with 17.9 MPa and 13.5 MPa for 13 % and 48 % of the gait cycle. In contrast ISO 14243-1:2009 (force controlled) showed three pressure maximums of 18.5 MPa (13 % of gait cycle), 16.4 MPa (48 % of gait cycle) and 13.2 MPa (75 % of gait cycle). The displacement controlled ISO (14243-3:2014) showed two pressure maximums of 16.0 MPa (13 % of gait cycle) and 17.2 MPa (48 % of gait cycle). The adapted force controlled ISO of the year 2009 showed higher mechanical stress during gait cycle which also might lead to higher wear rates. The displacement controlled ISO leads to higher mechanical stress because of the constraint at the end of the stance phase of the gait cycle. Future studies should analyse different inlay designs within these ISO standards

The meniscus is a fibrocartilaginous tissue that plays an important role in controlling the complex biomechanics of the knee. Many histological and mechanical studies about meniscal attachment have been carried out, and medial meniscus (MM) root repair is recommended to prevent subsequent cartilage degeneration following MM posterior root tear. However, there are only few studies about the differences between meniscus root and horn cells. The goal of this study was to clarify the differences between these two cells. Tissue samples were obtained from the medial knee compartments of 10 patients with osteoarthritis who underwent total knee arthroplasty. Morphology, distribution, and proliferation of MM root and horn cells, as well as gene and protein expression levels of Sry-type HMG box (SOX) 9 and type II collagen (COL2A1) were determined after cyclic tensile strain (CTS) treatment. Horn cells had a triangular morphology, whereas root cells were fibroblast-like. The number of horn cells positive for SOX9 and COL2A1 was considerably higher than that of root cells. Although root and horn cells showed similar levels of proliferation after 48, 72, or 96 h of culture, more horn cells than root cells were lost following 2-h CTS (5% and 10% strain). SOX9 and COL2A1 mRNA expression levels were significantly enhanced in horn cells compared with those in root cells after 2- and 4-h CTS (5%) treatment. This study demonstrates that MM root and horn cells have distinct characteristics and show different cellular phenotypes. Our results suggest that physiological tensile strain is important for activating extracellular matrix production in horn cells. Restoring physiological mechanical stress may be useful for promoting healing of the MM posterior horn

Objectives. In total hip arthroplasty (THA), the cementless, tapered-wedge stem design contributes to achieving initial stability and providing optimal load transfer in the proximal femur. However, loading conditions on the femur following THA are also influenced by femoral structure. Therefore, we determined the effects of tapered-wedge stems on the load distribution of the femur using subject-specific finite element models of femurs with various canal shapes. Patients and Methods. We studied 20 femurs, including seven champagne flute-type femurs, five stovepipe-type femurs, and eight intermediate-type femurs, in patients who had undergone cementless THA using the Accolade TMZF stem at our institution. Subject–specific finite element (FE) models of pre- and post-operative femurs with stems were constructed and used to perform FE analyses (FEAs) to simulate single-leg stance. FEA predictions were compared with changes in bone mineral density (BMD) measured for each patient during the first post-operative year. Results. Stovepipe models implanted with large-size stems had significantly lower equivalent stress on the proximal-medial area of the femur compared with champagne-flute and intermediate models, with a significant loss of BMD in the corresponding area at one year post-operatively. Conclusions. The stovepipe femurs required a large-size stem to obtain an optimal fit of the stem. The FEA result and post-operative BMD change of the femur suggest that the combination of a large-size Accolade TMZF stem and stovepipe femur may be associated with proximal stress shielding. Cite this article: M. Oba, Y. Inaba, N. Kobayashi, H. Ike, T. Tezuka, T. Saito. Effect of femoral canal shape on mechanical stress distribution and adaptive bone remodelling around a cementless tapered-wedge stem. Bone Joint Res 2016;5:362–369. DOI: 10.1302/2046-3758.59.2000525

Objective. Excessive mechanical stress on synovial joints causes osteoarthritis (OA) and results in the production of prostaglandin E2 (PGE2), a key molecule in arthritis, by synovial fibroblasts. However, the relationship between arthritis-related molecules and mechanical stress is still unclear. The purpose of this study was to examine the synovial fibroblast response to cyclic mechanical stress using an in vitro osteoarthritis model. Method. Human synovial fibroblasts were cultured on collagen scaffolds to produce three-dimensional constructs. A cyclic compressive loading of 40 kPa at 0.5 Hz was applied to the constructs, with or without the administration of a cyclooxygenase-2 (COX-2) selective inhibitor or dexamethasone, and then the concentrations of PGE2, interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), IL-6, IL-8 and COX-2 were measured. Results. The concentrations of PGE2, IL-6 and IL-8 in the loaded samples were significantly higher than those of unloaded samples; however, the concentrations of IL-1β and TNF-α were the same as the unloaded samples. After the administration of a COX-2 selective inhibitor, the increased concentration of PGE2 by cyclic compressive loading was impeded, but the concentrations of IL-6 and IL-8 remained high. With dexamethasone, upregulation of PGE2, IL-6 and IL-8 was suppressed. Conclusion. These results could be useful in revealing the molecular mechanism of mechanical stress in vivo for a better understanding of the pathology and therapy of OA. Cite this article: Bone Joint Res 2014;3:280–8

Military personnel operating on high speed marine craft are exposed to Whole-Body Vibration (WBV). Additionally planing craft operate at speeds with minimal contact of the hull with warer making the crew vulnerable to mechanical shock. An association between Low Back Pain (LBP) and exposure to WBV has been extensively reported in civilian literature. LBP is reported by military personnel operating on planing craft leading to downgrades and potential discharge. There is a clear need to understand the impact prolonged exposure has on our population operating these craft. We performed a bibliographical search of the PubMed database for records using a combination of keywords. Abstracts were screened for relevance and references cited in retrieved papers reviewed. There is no consensus in the literature on the potentially pivotal pathological process behind the association. Evidence from professional driving suggests current safe operating exposure levels require review to protect against long-term damage however with little evidence concerning the unique environment in which boats crews operate, the parity of these environments require investigation to allow direct comparison. Due to the prevalence of LBP in this population a need exists to establish the pathological process and add to the evidence base driving safe operating exposure levels.

Aims

This study aimed to demonstrate the promoting effect of elastic fixation on fracture, and further explore its mechanism at the gene and protein expression levels.

A recently developed parametric geometrical finite element model (p-FEM) was adapted to the specific hip geometric measurements of a group of patients with slipped capital femoral epiphysis (SCFE). The objective was to analyze the stress distribution in the growth plate of these patients and to evaluate differences for those patients who developed bilateral disease.

Different geometric parameters were measured in the healthy proximal femur of 18 adolescents (mean age, 12,1 yr) with unilateral SCFE and in 23 adolescents matched in age without hip disease (control group). Five patients developed SCFE in the contralateral side during follow-up. Different geometric measurements were taken from hip conventional X-ray studies. The p-FEM of the proximal femur permits modifications of different geometrical parameters, therefore the X-ray measurements taken from each patient were applied to the model obtaining a subject-specific model for each case. In each model, different mechanical situations such as walking, stairs climbing and sitting were simulated by applying loads on the femoral head corresponding to each own weight. The risk for growth plate failure was estimated by the Tresca, von Misses and Rankine stresses.

In summary, the models shows important differences between the stresses computed at the healthy femurs of patients with unilateral SCFE and femurs that further underwent bilateral SCFE. So, the 95% confidence interval of the percentage of volume of the growth plate subjected to stresses higher than 2MPa was almost similar for the control group and patients with unilateral SCFE. However, those patients who developed bilateral disease had statistically significant large physeal areas with more than 2.0 MPa (p< 0.005). Stresses were also strongly dependent on the geometry of the proximal femur, especially on the posterior sloping angle of the physis and the physeal sloping angle.

In spite of simplifications of the developed p-FEM, this tool has been able to show the influence of femur geometry in growth plate stresses and to predict the sites where growth plate starts to fail.

Aims. The presence of facet tropism has been correlated with an elevated susceptibility to lumbar disc pathology. Our objective was to evaluate the impact of facet tropism on chronic lumbosacral discogenic pain through the analysis of clinical data and finite element modelling (FEM). Methods. Retrospective analysis was conducted on clinical data, with a specific focus on the spinal units displaying facet tropism, utilizing FEM analysis for motion simulation. We studied 318 intervertebral levels in 156 patients who had undergone provocation discography. Significant predictors of clinical findings were identified by univariate and multivariate analyses. Loading conditions were applied in FEM simulations to mimic biomechanical effects on intervertebral discs, focusing on maximal displacement and intradiscal pressures, gauged through alterations in disc morphology and physical stress. Results. A total of 144 discs were categorized as ‘positive’ and 174 discs as ‘negative’ by the results of provocation discography. The presence of defined facet tropism (OR 3.451, 95% CI 1.944 to 6.126) and higher Adams classification (OR 2.172, 95% CI 1.523 to 3.097) were important predictive parameters for discography-‘positive’ discs. FEM simulations showcased uneven stress distribution and significant disc displacement in tropism-affected discs, where loading exacerbated stress on facets with greater angles. During varied positions, notably increased stress and displacement were observed in discs with tropism compared to those with normal facet structure. Conclusion. Our findings indicate that facet tropism can contribute to disc herniation and changes in intradiscal pressure, potentially exacerbating disc degeneration due to altered force distribution and increased mechanical stress. Cite this article: Bone Joint Res 2024;13(9):452–461

Abstract. Source of Study: London, United Kingdom. This intervention study was conducted to assess two developing protocols for quadriceps and hamstring rehabilitation: Blood Flow Restriction (BFR) and Neuromuscular Electrical Stimulation Training (NMES). BFR involves the application of an external compression cuff to the proximal thigh. In NMES training a portable electrical stimulation unit is connected to the limb via 4 electrodes. In both training modalities, following device application, a standardised set of exercises were performed by all participants. BFR and NMES have been developed to assist with rehabilitation following lower limb trauma and surgery. They offer an alternative for individuals who are unable to tolerate the high mechanical stresses associated with traditional rehabilitation programmes. The use of BFR and NMES in this study was compared across a total of 20 participants. Following allocation into one of the training programmes, the individuals completed training programmes across a 4-week period. Post-intervention outcomes were assessed using Surface Electromyography (EMG) which recorded EMG amplitude values for the following muscles: Vastus Medialis, Vastus Lateralis, Rectus Femoris and Semitendinosus. Increased Semitendinosus muscle activation was observed post intervention in both BFR and NMES training groups. Statistically significant differences between the two groups was not identified. Larger scale randomised-controlled trials are recommended to further assess for possible treatment effects in these promising training modalities

Low back pain is the single most common cause for disability in individuals aged 45 years or younger, it carries tremendous weight in socioeconomic considerations. Degenerative aging of the structural components of the spine can be associated with genetic aspects, lifetime of tissue exposure to mechanical stress & loads and environmental factors. Mechanical consequences of the disc degenerative include loss of disc height, segment instability and increase the load on facets joints. All these can lead to degenerative changes and osteophytes that can narrow the spinal canal. Surgery is indicated in patients with spinal stenosis who have intractable pain, altered quality of life, substantially diminished functional capacity, failed non-surgical treatment and are not candidates for non-surgical treatment. The aim was to determine the reasons for refusal of surgery in patients with established degenerative lumber spine pathology eligible for surgery. All patients meeting the study criteria, patients older than 18 years, patients with both clinical and radiological established symptomatic degenerative lumbar spine pathology and patients eligible for surgery but refusing it were recruited. Questionnaire used to investigate reasons why they are refusing surgery. Results 59 were recruited, fifty-one (86.4 %) females and eight (13.6 %) males. Twenty (33.8 %) were between the age of 51 and 60 years, followed by nineteen (32.2 %) between 61 and 70 years, and fourteen (23.7 %) between 71 and 80 years. 43 (72 %) patients had lumber spondylosis complicated by lumber spine stenosis, followed by nine (15.2 %) with lumbar spine spondylolisthesis and four (6.7 %) had adjacent level disease. 28 (47.4 %) were scared of surgery, fifteen (25.4 %) claimed that they are too old for surgery and nine (15.2 %) were not ready. Findings from this study outlined that patients lack information about the spinal surgery. Patients education about spine surgery is needed

Varus malalignment increases the susceptibility of cartilage to mechanical overloading, which stimulates catabolic metabolism to break down the extracellular matrix and lead to osteoarthritis (OA). The altered mechanical axis from the hip, knee to ankle leads to knee joint pain and ensuing cartilage wear and deterioration, which impact millions of the aged population. Stabilization of the remaining damaged cartilage, and prevention of further deterioration, could provide immense clinical utility and prolong joint function. Our previous work showed that high tibial osteotomy (HTO) could shift the mechanical stress from an imbalanced status to a neutral alignment. However, the underlying mechanisms of endogenous cartilage stabilization after HTO remain unclear. We hypothesize that cartilage-resident mesenchymal stem cells (MSCs) dampen damaged cartilage injury and promote endogenous repair in a varus malaligned knee. The goal of this study is to further examine whether HTO-mediated off-loading would affect human cartilage-resident MSCs' anabolic and catabolic metabolism. This study was approved by IACUC at Xi'an Jiaotong University. Patients with medial compartment OA (52.75±6.85 yrs, left knee 18, right knee 20) underwent open-wedge HTO by the same surgeons at one single academic sports medicine center. Clinical data was documented by the Epic HIS between the dates of April 2019 and April 2022 and radiographic images were collected with a minimum of 12 months of follow-up. Medial compartment OA with/without medial meniscus injury patients with unilateral Kellgren /Lawrence grade 3–4 was confirmed by X-ray. All incisions of the lower extremity healed well after the HTO operation without incision infection. Joint space width (JSW) was measured by uploading to ImageJ software. The Knee injury and Osteoarthritis Outcome Score (KOOS) toolkit was applied to assess the pain level. Outerbridge scores were obtained from a second-look arthroscopic examination. RNA was extracted to quantify catabolic targets and pro-inflammatory genes (QiaGen). Student's t test for two group comparisons and ANOVA analysis for differences between more than 2 groups were utilized. To understand the role of mechanical loading-induced cartilage repair, we measured the serial changes of joint space width (JSW) after HTO for assessing the state of the cartilage stabilization. Our data showed that HTO increased the JSW, decreased the VAS score and improved the KOOS score significantly. We further scored cartilage lesion severity using the Outerbridge classification under a second-look arthroscopic examination while removing the HTO plate. It showed the cartilage lesion area decreased significantly, the full thickness of cartilage increased and mechanical strength was better compared to the pre-HTO baseline. HTO dampened medial tibiofemoral cartilage degeneration and accelerate cartilage repair from Outerbridge grade 2 to 3 to Outerbridge 0 to 1 compared to untreated varus OA. It suggested that physical loading was involved in HTO-induced cartilage regeneration. Given that HTO surgery increases joint space width and creates a physical loading environment, we hypothesize that HTO could increase cartilage composition and collagen accumulation. Consistent with our observation, a group of cartilage-resident MSCs was identified. Our data further showed decreased expression of RUNX2, COL10 and increased SOX9 in MSCs at the RNA level, indicating that catabolic activities were halted during mechanical off-loading. To understand the role of cartilage-resident MSCs in cartilage repair in a biophysical environment, we investigated the differentiation potential of MSCs under 3-dimensional mechanical loading conditions. The physical loading inhibited catabolic markers (IL-1 and IL-6) and increased anabolic markers (SOX9, COL2). Knee-preserved HTO intervention alleviates varus malalignment-related knee joint pain, improves daily and recreation function, and repairs degenerated cartilage of medial compartment OA. The off-loading effect of HTO may allow the mechanoregulation of cartilage repair through the differentiation of endogenous cartilage-derived MSCs

Hip instability is one of the most common complications after total hip arthroplasty (THA). Among the possible techniques to treat and prevent hip dislocation, the use of constrained liners is a well-established option. However, there is concern regarding the longevity of these devices due to higher mechanical stress caused by limited hip motion. The primary aim of this paper is to analyze the failure rate of a specific constrained liner in a series of consecutive cases. This study is a retrospective consecutive case series of THA and revision hip arthroplasty (RHA), in which a constrained polyethylene insert was used to treat or prevent hip instability. Patients were divided in 3 different groups (THA for hip fracture, THA for osteoarthrosis, and RHA). Survival analysis was performed for failure, defined as at least one episode of hip dislocation or radiographical signs of acetabular loosening. Logistical regression was used to investigate risk factors for failure. A total of 103 patients were included in the study. Fourteen patients (13,6%) were THA for osteoarthrosis, 60 (58,3%) were THA for hip fracture, and 29(28,2%) were RHA. The median follow-up was 28 months (ranging 12 − 173 months). Failure occurred in 4 cases (3,9%) comprehending 2 dislocations (1,9%) and 2 early acetabular loosening (1,9%). Amongst the groups, there were no cases of failures in the THA due to osteoarthrosis, in the THA for hip fracture there were 3 cases (5%) and in the RHA one case (3,4%). Failure-free survival was not statistically different between groups. There were no risk factors statistically related to failure. The use of constrained acetabular insert to prevent or treat instability achieved an adequate survival time with a low rate of complications. Further studies are necessary to corroborate our findings

Biomechanical analysis is important to evaluate the effect of orthopaedic surgeries. CT-image based finite element method (CT-FEM) is one of the most important techniques in the computational biomechanics field. We have been applied CT-FEM to evaluate resorptive bone remodeling, secondary to stress shielding, after total hip arthroplasty (THA). We compared the equivalent stress and strain energy density to postoperative BMD (bone mineral density) change in the femur after THA, and a significant correlation was observed between the rate of changes in BMD after THA and equivalent stress. For periacetabular osteotomy cases, we investigated mechanical stress in the hip joint before and after surgery. Mechanical stress in the hip joint decreased significantly after osteotomy and correlated with the degree of the acetabular coverage. For arthroscopic osteochondroplasty cases, we examined mechanical strength of the proximal femur after cam resection using CT-FEM. The results suggested that both the depth and area of the resection at the distal part of femoral head-neck junction correlated strongly with fracture risk after osteochondroplasty. This talk consists of our results of clinical application studies using CT-FEM, and importance of application of CT-FEM to biomechanical studies to assess the effect of orthopaedic surgeries

Introduction. The low-contact stress (LCS) knee prosthesis is a mobile-bearing design with modifications to the tibial component that allow for meniscal-bearing (MB) or rotating-platform (RP). The MB design had nonconstrained anteroposterior and rotational movement, and the RP design has only nonconstrained rotational movement. The anterior soft tissues, including patellar tendon (PT), prevent anterior dislocation of the MB. The PT may consistently be exposed to overstressing. Therefore, we hypothesized that the PT thickness and width in MB prosthesis revealed more morphological changes than those of RP prosthesis due to degeneration of the PT induced by much mechanical stress of the MB movement. To confirm this hypothesis, we analyze the PT thickness and width induced by mobile-bearing inserts. Objectives. Sixty LCS prostheses in 30 patients were analyzed. The average follow-up time was 61 months. MB prosthesis was used on one side of the knee and RP prosthesis was used on the contralateral side of the knee. All patients were chosen from group with no clinical complication, and all had achieved passive full extension and at least 90°of flexion. The average Hospital for Special Surgery Score was 94.6 ± 2.7. Methods. We measured the thickness and width of PT at joint line level, which were confirmed by sagittal section using ultrasound in knee extension between MB and RP design prosthesis. Results. The mean thickness of PT was 4.7 mm (1.2) with MB and 4.7 mm (1.0) with RP design prosthesis. The mean width of PT was 30.6 mm (3.2) with MB and 31.3 mm (3.5) with RP design prosthesis. No significant differences were found between both groups. Conclusion. The current results showed that the PT thickness and width in MB prosthesis did not reveal more morphological changes than those of RP prosthesis due to degeneration of the PT induced by much mechanical stress of the MB movement. The possible reasons are the following: (1) We did not remove infra-patellar fat pad, which might play shock absorber of mechanical stress from MB, and prevent from significant degeneration of PT, (2) MB inserts did not stimulate the middle of the PT directly, unlike LCS A/P-Glide inserts, and might come into contact with the both ends of the PT and (3) MB inserts did not move so as to cause degeneration in the PT

Introduction and Objective. Anterior cruciate ligament reconstruction (ACLR) with tendon autografts is the “gold standard” technique for surgical treatment of ACL injuries. Common tendon graft choices include patellar tendon (PT), semitendinosus/gracilis “hamstring” tendon (HT), or quadriceps tendon (QT). Healing of the graft after ACLR may be affected by graft type since the tissue is subjected to mechanical stresses during post-operative rehabilitation that play important roles in graft integration, remodeling and maturation. Abnormal mechanical loading can result in high inflammatory and degradative processes and altered extracellular matrix (ECM) synthesis and remodeling, potentially modifying tissue structure, composition, and function. Because of the importance of load and ligamentization for tendon autografts, this study was designed to compare the differential inflammatory and degradative metabolic responses to loading by three tendon types commonly used for autograft ACL reconstruction. Materials and Methods. With IRB approval (IRB # 2009879) and informed patient consent, portions of 9 QT, 7 PT and 6 HT were recovered at the time of standard of care ACLR surgeries. Tissues were minced and digested in 0.2 mg/ml collagenase solution for two hours and were then cultured in 10% FBS at 5% CO. 2. , 37°C, and 95% humidity. Once confluent, cells were plated in Collagen Type I-coated BioFlex® plates (1 × 10. 5. cells/well) and cultured for 2 days prior to the application of strain. Then, media was changed to supplemented DMEM with 2% FBS for the application of strain. Fibroblasts were subjected to continuous mechanical stimulation (2-s strain and 10-s relaxation at a 0.5 Hz frequency) at three different elongation strains (mechanical stress deprivation-0%, physiologic strain-4%, and supraphysiological strain-10%). 9. for 6 days using the Flexcell FX-4000T strain system. Media was tested for inflammatory biomarkers (PGE2, IL-8, Gro-α, and MCP-1) and degradation biomarkers (GAG content, MMP-1, MMP-2, MMP-3, TIMP-1, and TIMP-2). Significant (p<0.05) difference between graft sources were assessed with Kruskal-Wallis test and post-hoc analysis. Results are reported as median± interquartile range (IQR). Results. Differences in Inflammation-Related Biomarker Production (Figure 1): The production of PGE2 was significantly lower by HT fibroblasts compared to both QT and PT fibroblasts at all timepoints and strain levels. The production of Gro-α was significantly lower by HT fibroblasts compared to QT at all time points and strain levels, and significantly lower than PT on day 3 at 0% strain, and all strain levels on day 6. The production of IL-8 by PT fibroblasts was significantly lower than QT and HT fibroblast on day 3 at 10% strain. Differences in Degradation-Related Biomarker Production (Figure 2): The production of GAG by HT fibroblasts was significantly higher compared to both QT and PT fibroblasts on day 6 at 0% strain. The production of MMP-1 by the QT fibroblasts was significantly higher compared to HT fibroblasts on day 3 of culture at all strain levels, and in the 0% and 10% strain levels on day 6 of culture. The production of MMP-1 by the QT fibroblasts was significantly higher compared to PT fibroblasts at in the 0% and 4% strain groups on day 3 of culture. The production of TIMP-1 by the HT fibroblasts was significantly lower compared to PT fibroblasts on day 3 of culture. Conclusions. The results of this study identify potentially clinically relevant difference in the metabolic responses of tendon graft fibroblasts to strain, suggesting a lower inflammatory response by hamstring tendon fibroblasts and higher degradative response by quadriceps tendon fibroblasts. These responses may influence ACL autograft healing as well as inflammatory mediators of pain in the knee after reconstruction, which may have implications regarding graft choice and design of postoperative rehabilitation protocols for optimizing outcomes for patients undergoing ACL reconstruction. For any figures or tables, please contact the authors directly

Background. Medical applications of nanotechnology are promising because it allows the surface of biomaterial to be tailored to optimise the interfacial interaction between the biomaterial and its biological environment. Such interfaces are of interest in the domain of orthopaedic surgery as they could have anti-bacterial functions or could be used as drug delivery systems. The development of orthopaedics is moving towards better integration of biology in implants and surgical techniques, but the mechanical properties of implanted materials are still important for orthopaedic applications. During clinical implantation, implants are subjected to large mechanical stresses. In order to obtain the best performance during clinical use, mechanical properties of implants need to be investigated and understood. Method. We modified the topography of commercial titanium orthopaedic screws using electrochemical anodization in a 0.4 wt% hydrofluoric acid solution to produce titanium dioxide nanotube layers. The morphology of the nanotube layers were characterised using scanning electron microscopy. The mechanical properties of the nanotube layers were investigated by screwing and unscrewing an anodized screw into several different types of human bone while the torsional force applied to the screwdriver was measured using a torque screwdriver. The range of torsional force applied to the screwdriver was between 5 and 80 cN·m. Independent assessment of the mechanical properties of the same surfaces was performed on simple anodized titanium foils using a triboindenter. Results. The fabricated nanotube layers can resist mechanical stresses close to those found in clinical situations. Conclusion. The mechanical characteristics of this surface treatment appear to be sufficiently robust to withstand realistic clinical operating conditions that our in vitro experiments were designed to simulate. These results show that the nanotube layers remain intact after the implantation process. This may allow for the exciting possibility of nanotubes being loaded with molecules. Level of Evidence. II

Introduction: Two second generation highly crosslinked UHMWPEs have been cleared by the FDA for clinical use in the United States: sequentially crosslinked UHMWPE (X3™ UHMWPE, Stryker Inc., Mahwah, NJ, USA) and α-tocopherol stabilized UHMWPE (E-Poly™ UHMWPE, Biomet, Inc., Warsaw, IN, USA). Both have been shown to be oxidatively stable under standardized aging methods (ASTM F2003); however, these conventional aging methods did not consider the effect of mechanical loading on the oxidative behavior of the materials. By coupling the adverse effects of thermal aging and mechanical stress, we sought to investigate if either material was prone to environmental stress cracking (ESC). We hypothesize that the residual free radicals remaining in sequentially crosslinked PE will lead to oxidative degradation in this adverse test; furthermore, we hypothesized that the α-tocopherol infused in E-Poly™ will continue to protect the highly crosslinked PE even under such unfavorable conditions. Materials and Methods: Three materials were tested:. Conventional: UHMWPE gamma sterilized in inert,. SXL: sequentially irradiated and annealed UHMWPE irradiated to a cumulative dose of 100kGy (33 kGy irradiation + 8 hour annealing in air, repeated 3 times) and gas plasma sterilized, and. E-Poly: UHMWPE irradiated to 100kGy, stabilized with α-tocopherol, and gamma sterilized in inert. Four specimens from each group were subjected to a reciprocating mechanical stress of 10 MPa at a frequency of 0.5 Hz in an environmental chamber maintained at 80°C. Control samples were placed in the chamber but not subjected to cyclic mechanical stress. When a visible crack was observed on a sample’s surface or when a sample fractured, it and its corresponding control sample were analyzed by FTIR to quantify oxidation. Results: All conventional specimens, half (2 of 4) of the SXL specimens, and none of the E-Poly specimens failed prior to the completion of 1,530,000 cycles (5 weeks of testing at 0.5 Hz). Cyclic loading had an adverse effect on the oxidation of the conventional and the SXL groups; the peak oxidation levels were higher in the cyclically loaded samples as compared to the control samples removed at the same time which were not loaded, likely due to an increase in chain scission induced by the mechanical load. The E-Poly specimens did not fail during the 5 weeks of testing, and FTIR did not reveal detectable oxidation in either control or loaded samples. Discusssion and conclusion: Though the sequential processing of SXL creates a material with a lower free radical content compared to once-annealed material, it still yields a material prone to oxidation under extreme conditions, raising questions about its long-term oxidative stability. E-Poly™, protected by α-tocopherol, continues to exhibit high oxidation resistance even under adverse conditions

The structure and extracellular matrix composition of the interface are complex and allow for a gradual mechanical stress transfer between tendons and bone. In this study, biphasic silk fibroin scaffolds designed to mimic the gradient in collagen molecule alignment present at the interface. The scaffolds had two different pore alignments: anisotropic at the tendon side and isotropic at the bone side. Total porosity ranged from 50–80% and the majority of pores were <100–300 µm. Young's modulus varied from 689–1322 kPa. In addition, human adMSC were cultured on the scaffolds to evaluate the effect of pore morphology on cell proliferation and gene expression. Biphasic scaffolds supported cell attachment and influenced cytoskeleton organization depending on pore alignment. In addition, the gene expression of tendon, enthesis and cartilage markers significantly changed in each region of the scaffolds. We functionalized those scaffolds with heparin and explored their ability to deliver TGF-β2 and GDF5. TGF-β2 and pore anisotropy synergistically increased the expression of tendon/ligament markers and collagen I protein content. The combined delivery of TGF-β2 and GDF5 enhanced the expression of cartilage markers and collagen II protein content on substrates with isotropic porosity, whereas enthesis markers were enhanced in areas of mixed anisotropic/isotropic porosity

In recent years, novel therapies for intervertebral disc (IVD) regeneration have been developed that are based on the delivery of cells, biomaterials or bioactive molecules. The efficacy of these biological therapies depends on the type and degree of IVD degeneration. Whole organ culture bioreactors provide an attractive platform for pre-clinical testing of IVD therapeutics, since the cells are maintained within their native extracellular matrix, and the endplate remains intact to fulfil its function. Moreover, defined regimes of mechanical stress are applied to the IVD, representing either physiological or degenerative, detrimental loading. Different degrees of degeneration can be induced by high load, low nutrition, enzyme injection, and/or mechanical damage; while recent organ culture models also implement an inflammatory component. Using whole organ culture models, we found that mesenchymal stem cell injection into nucleotomized IVDs had an anabolic effect on the IVD cells. Furthermore, hyaluronan hydrogels were beneficial for cell delivery and mechanical support. We also found that anti-inflammatory treatment could partially prevent the induction of cytokines in an inflammatory model. However, chemokine delivery did not induce a significant repair response in an annulus fibrosus defect. In line with 3R principles, relevant ex-vivo models are essential to reliably test biological IVD treatments