Between 2016–2019, 4 patients developed hip infections post-hemiarthroplasty. However, between 2020–2021 (Covid-19 pandemic period), 6 patients developed hip infections following hip hemiarthroplasty. The purpose of the investigation is to establish the root causes and key learning from the incident and use the information contained within this report to reduce the likelihood of a similar incident in the future. 65 patients presented with a neck of femur fracture during Covid-19 pandemic period between 2020–2021, 26 had hip hemiarthroplasty of which 6 developed hip infections. Medical records, anaesthetic charts and post-hip infections guidelines from RCS and NICE were utilised. Proteus, Enterococci and Strep. epidermis were identified as the main organisms present causing the hip infection. The average number of ward moves was 4 with 90% of patients developing COVID-19 during their hospital stay. The chance of post-operative wound infection were multifactorial. Having had 5 of 6 patients growing enterococci may suggest contamination of wound either due to potential suboptimal hygiene measures, inadequate wound management /dressing, potential environmental contamination if the organisms (Vancomycin resistant enterococci) are found to be of same types and potential hospital acquired infection due to inadequate infection control measures or suboptimal hand hygiene practices. 3 of the 5 patients grew Proteus, which points towards suboptimal hygiene practices by patients or poor infection control practices by staff. Lack of maintenance of sterility in post op wound dressings alongside inexperience of the handling of post-operative wound in non-surgical wards; multiple ward transfers exceeding the recommended number according to trust guidelines especially due to pandemic isolation measures and COVID-19 infection itself had resulted in an increased rate of hip infections during the COVID-19 pandemic. Multidisciplinary team education and planned categorisation and isolation strategy is essential to minimise the rate of further hip infections during the pandemic period in future

Infections in spine surgery are relatively common and devastating complications, a significant burden to the patient and the healthcare system. Usually, the treatment of SSIs consists of aggressive and prolonged antibiotic therapy, multiple debridements, and in chronic cases, hardware removal. Infections are correlated with worse subjective outcomes and even higher mortality. Depending on the type of spine surgery, the infection rate has been reported to be as higher as 20%. Recently silver-coated implants have been introduced in spine surgery to reduce the incidence of post-operative infections and to improve implant survivorship. The aim of the present study is to evaluate complications and outcomes in patients treated with silver-coated implants because of spine infection. All consecutive patients who had spine stabilization with a silver-coated implant from 2018 to 2021 were screened for inclusion in the study. Inclusion criteria were: (1) six months of minimum follow-up; (2) previous surgical site infection; hematogenous spondylodiscitis requiring surgical stabilization. Demographic and surgical information were obtained via chart review, all the device-related complications and the reoperation rate were also reported. A total of 57 patients were included in the present study. The mean age was 63.4 years, and there were 36 (63%) males and 21 (37%) females. Among the included cases, 57% were SSIs, 33% were spondylodiscitis, and 9% were hardware mobilization. Comorbidities such as diabetes mellitus, obesity, smoke, and oncological history were significant risk factors. In addition, the organisms cultured were Staphylococcus species in most of the cases. At six months of follow-up, 40% of patients were considered free from infection, while 20% needed multiple surgeries. The present research showed satisfactory results of silver-coated implants for the treatment of spine infection

To determine risk factors of infection in total knee arthroplasty. This descriptive study was conducted in the Department of Orthopedics for a duration of three years from January 2016 to January 2019. All patients undergoing primary total knee replacement were included in the study. Exclusion criteria were all patients operated in another hospital and revision total knee replacement. All patients were followed up at 2, 4, 8, 12 and 24 weeks post-operatively. Signs of inflammation and inflammatory markers such as total leukocyte count (TLC), C-reactive protein (CRP) and ESR were measured. Risk factors like age, body mass index (BMI), ASA, co-morbid conditions were also noted. A total of 78 patients underwent primary unilateral Total Knee Replacement (TKR) during the study period. Of these, 30 (34.09%) were male and 48 (61.54%) female patients. Mean age of patients was 68.32 ± 8.54 years. Average BMI 25.89 Kg/m2 .Osteoarthritis was the pre-dominant cause of total knee replacement (94.87%). Among co-morbid factors 33.33% were diabetic, 28.20% having ischemic heart disease and 12.82% with chronic lung disease. Upon anaesthesia fitness pre-operatively, 91.02% patients had an American society of anaesthesiologist score (ASA) between 0–2 while 07 (8.97%) between 3- 5. Average duration of surgery was 85.62± 4.11 minutes. 6.41% cases got infected. In majority of the infected cases (60%), Staphylococcus aureus was the infective organism. Diabetes Mellitus (p=0.01) and Obesity (p=0.02) had a significant relation to post-operative infection. Pre-operative risk evaluation and prevention strategies along with early recognition of infection and control can greatly reduce the risk of joint infection post-TKR which will not only improve the mobility of patient but also its morbidity and mortality as well. Key Words:. C-reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR), Staphylococcus aureus, Total Knee Arthroplasty (TKA)

Platelet Rich Plasma (PRP), either rich (L-PRP) or poor (P-PRP) of leukocytes, is frequently used as an anti-inflammatory and regenerative tool in osteoarthritis (OA). PRP contains proteins but not genes as it is derived from megakaryocytes. Proteomics but not metabolomics of PRP was recently studied. Metabolomics is a field of ‘omics’ research involved in comprehensive portrayal of the small molecules, metabolites, in the metabolome. These small molecules can be endogenous metabolites or exogenous compounds found in an organism (1). Our aim was to determine the difference between L-PRP and P-PRP. A cross-sectional clinical study was designed in six recreational male athletes between the ages of 18 and 35 years. 3 mL P-PRP and 3 mL -LPRP was prepared from 60 mL of venous blood after treating with 9 mL of sodium citrate and centrifugation at 2.700 rpm for 10 min. Half of the prepared PRP's were frozen at −20°C for a week. Fresh and frozen samples were analyzed at the Q-TOF LC/MS device after thawing to room temperature. Untargeted metabolomic results revealed that the metabolomic profile of the L-PRP and P-PRP were significantly different from each other. A total of 33.438 peaks were found. Statistically significant (p<0.05) peaks were uploaded to the MetaboAnalyst 5.0 platform. Exogenous out of 2.308 metabolites were eliminated and metabolites found significant for our study were subjected to pathway analysis. Steroid biosynthesis, sphingolipid metabolism and metabolism of lipid pathways were affected. In the L-PRP samples, Nicotinamide riboside (FC: 2.2), MHPG (FC: 3.0), estrone sulfate (FC: 7.5), thiamine diphosphate (FC: 2.0), leukotriene E4 (FC: 7.5), PC(18:1 (9Z)e/2:0) (FC: 9.8) and Ap4A (FC: 2.1) were higher compared to P-PRP. C24 sulfatide (FC: −11.8), 3-hexaprenyl-4,5-dihydroxybenzoic acid (FC: −2.8) metabolites were furthermore lower in P-PRP. Clinical outcomes of PRP application should consider these metabolic pathways in future studies (2)

Current strategies for bone repair have accepted limitations and the search for synthetic graft materials or for scaffolds that will support ex vivo bone tissue engineering continues. Bioprospecting has led to increased interest in potential applications for marine organisms and their by-products and biomimetic strategies have led to the investigation of naturally occurring porous structures as templates for bone growth. As a rich source of mineralising porous organisms, our seas and oceans could provide new directions for bone tissue engineering that may enhance in vivo and ex vivo bone formation

Femoral impaction bone grafting (IBG) may be used to restore bone stock in revision total hip arthroplasty (THA) and allow use of a shorter, than otherwise, length prosthesis. This is most beneficial in young patients who are more likely to require further revision surgery. This study aimed to assess the results of femoral IBG for staged revision THA for infection. A prospective cohort of 29 patients who underwent staged revision THA for infection with femoral IBG and a cemented polished double-tapered (CPDT) stem at the final reconstruction was investigated. The minimum follow-up was two years (2 – 10 years, median 6 years). Stem subsidence was measured with radiostereometric analysis. Clinical outcomes were assessed with the Harris Hip, Harris Pain, and and Société Internationale de Chirurgie Orthopédique et de Traumatologie Activity (SICOT) Scores. The original infection was eradicated in 28 patients. One patient required a repeat staged revision due to re-infection with the same organism. At two-year follow-up, the median subsidence at the stem-bone interface was −1.70 mm (−0.31 to −4.98mm). The median Harris Hip Score improved from 51 pre-operatively to 80 at two years (p=0.000), the Harris Pain Score from 20 to 44 (p=0.000) and the SICOT Score from 2.5 to 3 (p=0.003). As successful eradication of infection was achieved in the majority of patients and the stem migration was similar to that of a primary CPDT stem, this study supports the use of femoral IBG during the final reconstruction of the femur after staged revision THA for infection

Background. We herein report a case of isolated hip pain in a four year old boy. The unique aspect of this case study is the unusual history, presentation, ultrasonography, MRI and blood culture results, which lead to the diagnosis and treatment of adductor pyomyositis with a rare organism (Streptococcus Mitis) in a temperate country. The objectives of this case study is to discuss the key learning outcomes with respect to assessment and management of this case. Methods. The patient presented with a one day history of malaise, fever, left groin pain and inability to weight bear on the left leg. There was no history of any trauma, predisposing infections or recent travel. A working diagnosis of transient synovitis / septic arthritis of the hip was made on clinical examination. Results. Plain radiograph and ultrasound of the hip was normal with no effusion. Two consecutive blood cultures suggested Streptococcus Mitis bacteriaemia and MRI scan confirmed pyomyositis of the left hip adductors that was too small to drain. Streptococcus Mitis is a normal commensal organism of the oral cavity however it can lead to opportunistic infections particularly endocarditis. Echocardiogram revealed no cardiac complications, in particular no endocarditic vegetation. Patient was treated with intravenous benzylpenicillin for a week followed by oral phenoxymethylpenicillin for a week. Conclusion. Adductor pyomyositis must be considered as a differential diagnosis in a child with unusual presentation of hip pain. When an ultrasound is normal, MRI scan is warranted to confirm diagnosis. Septic screen should include blood cultures. The commonest causative organisms are the Staphylococcus family. However if Streptococcus Mitis is isolated, cardiac sources of infection resulting in septic emboli must be investigated. Repeated MRI scans are required particularly if the patient does not respond to medical management. Level of Evidence. IV

Intro. Calcium sulphate (CS) is a recent alternative for antibiotic elution in infected bones and joints. The purpose of this study is to evaluate the use of antibiotic impregnated calcium sulphate (AICS) beads in the management of infected tibia and femur, with regards to patient outcomes and complication rates (including reinfection rate, remission rate and union rate). Methods. Searches of AMED, CINAHL, EMBASE, EMCARE, Medline, PubMed and Google Scholar were conducted in June 2020, with the mesh terms: “Calcium sulphate beads” or “Calcium sulfate beads” or “antibiotic beads” or “Stimulan” AND “Bone infection” or “Osteomyelitis” or “Debridement” AND “Tibia” or “Femur”. Risk of bias was assessed using the Risk of Bias in Non-randomised Studies of interventions (ROBINS-i) tool, and quality assessed via the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria. Results. Out of 105 relevant papers, 11 met the inclusion criteria for data extraction. Total infection recurrence rate was 6.8% (range 3.2 – 11.9%, n = 295), which was significantly lower (p < 0.001) than that of polymethylmethacrylate (PMMA; 19.6%, n = 163). Complication rates varied. The main issue regarding AICS use was wound drainage (7.9 – 33.3%), which was considerably higher in studies involving treatment of the tibia only. Studies using PMMA did not experience this issue, but there were a few incidences of superficial pin tract infection following surgery. Conclusions. AICS was consistently effective at infection eradication, despite variation in causative organism and location of bead placement. Additionally, PMMA has many inconvenient properties. AICS is therefore an attractive alternative as an adjunct in treatment of infected tibia and femur. Wound drainage rate varied and was higher in studies regarding tibial cases alone

Two major challenges in arthroplasty are obesity and antibiotic resistance. This study was performed to characterise the organisms responsible for deep infection following total hip arthroplasty and to determine if obesity affected the microbiology profile. A retrospective analysis of the national surgical site infection register was made to obtain data regarding deep infection following 10948 primary total hip arthroplasty (THA) from 1998–2013, with a minimum of 2 year follow-up. Of all the primary THAs performed, there were 108 deep infections (56 patients had a BMI >30 (obese) and 52 patients <30). There were no significant differences between cardio-respiratory disease, smoking and alcohol status, and diabetes between the 2 groups. Over the last 15 years, staphylococcus aureus continues to be the most frequently isolated organism. Infection with multiple organisms was found exclusively in obese patients. Furthermore, in obese patients, there was a linear increase with methicillin resistant staphylococcus aureus (MRSA) infections and streptococcus viridans. On this basis, we recommend careful selection of antibiotic therapy in obese patients, rather than empirical therapy, which can be especially important if there is no growth in an infected THA. In addition, a preoperative discussion regarding dental prophylaxis against streptococcus viridans may be warranted

Late infection is the most frequent complications after hemiarthroplasty. Urinary tract infections are the only distant septic focus considered to be a risk factor in the literature. We retrospectively reviewed 460 patients with hip fracture treated by hemiarthroplasy over a period of one year. Preoperative positive urine dipsticks and urine analysis have been looked at as causes for delay of surgery in absence of clinical manifestations of urinary tract infection. 367 patients were operated within 24 hours. 78 patients were delayed more than 78 hours. Urinary tract infection had the least contribution as a cause of delay. 99 patients had preoperative urinary tract infection and 57 patients had postoperative wound infection. Of these with postoperative surgical site infection, 31 patients did not show any evidence of preoperative urinary tract infection, 23 patients had preoperative urinary tract infection, two had leg ulcer and one had chest infection. 13 patients had chronic urinary tract infection and five patients had the same causative organism in urine & wound. The most common organisms of urinary infection are E. Coli, mixed growth, Enteroccocus Faecalis, Pseudomonas and others. The most causative organism of the postoperative surgical site infection are Staph aureus including MRSA, mixed growth including Staph. Epidermidis, Enteroccocus Faecalis and others There is no direct significant correlation between preoperative urinary tract infection and surgical site infection. We recommend that preoperative urinary tract infection should be treated as a matter of urgency but it should not delay hip fracture surgery unless it is causing symptoms

Aims

This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation.

Device-associated infection remains a serious clinical problem in orthopaedic and trauma surgery. The emergence of resistant organisms such as methicillin resistant Staphylococcus aureus (MRSA) has further exacerbated this problem by limiting the range of treatment options. Currently, systemic antibiotic therapy is the cornerstone of treatment, alongside surgical resection of infected tissues and implant removal. The potential for antibiotic loaded biomaterials to support the prevention and treatment of infection is significant, although the currently available options are limited in number and often re-purposed from other applications e.g. antibiotic loading of bone cement. The first part of the talk will cover the basic concepts involved in antibiotic treatment, with an emphasis on the ideal antibiotic release kinetics from biomaterials, and how bacterial biofilms and antibiotic resistance influence antimicrobial efficacy. The next generation of biomaterials for antibiotic delivery should be specifically designed with this knowledge in mind. Regulatory approval of antimicrobial combination devices, however, is an evolving process as regulatory bodies seek more robust and clinically relevant efficacy data. Approval will require preclinical efficacy using standardized animal models that recapitulate the key features of the clinical disease. The second part of this talk will cover best practice in this important stage of development

Current cell-based tissue engineering strategies have limited clinical applicability due to the need for large cell numbers and prolonged culture periods that lead to phenotypic drift. In vitro microenvironmental modulators have been proposed to mimic the native tendon. Standard in vitro culture conditions result in delayed extracellular matrix (ECM) deposition, impairing the development of scaffold-free approaches. ECM deposition can be enhanced by macromolecular crowding (MMC), a biophysical phenomenon that governs the milieu of multicellular organisms. We assessed a multifactorial biophysical approach, using MMC and mechanical loading, on different cell sources to determine their suitability for in vitro fabrication of tendon-like tissue. Human dermal fibroblasts (DFs), tenocytes (TCs) and bone marrow mesenchymal stem cells (BMSCs) were cultured with MMC under static and uniaxial strain culture conditions. TCs and DFs exhibited alignment perpendicular to the load, whilst BMSCs did not show preferential alignment. When MMC was used, DFs and BMSCs showed increased deposition of collagen I, the main component in tendon ECM. DFs presented ECM composition similar to TCs with collagen types III, V and VI present. Gene expression analysis revealed upregulation of tenogenic markers by TCs and DFs, such as scleraxis and thrombospondin-4, under both loading and MMC. The combined use of MMC and mechanical stimulation is suitable for TCs phenotype maintenance and can modulate the phenotype of DFs and BMSCs differentially. This study provides insight into response of different cell sources to biophysical cues and contributes to further development of cell therapies for tendon repair and regeneration

Prosthetic Joint Infections (PJIs) are increasing with the use of orthopedic devices on an ageing population. Cutibacterium acnes is a commensal organism that plays an important role in the ecosystem healthy human skin, yet this species is also recognized as a pathogen in foreign body infection: endocarditis, prostatitis and specifically in PJIs. C. acnes is able to escape the immune system. This phenomenon could reflect two bacterial behaviour: the bacterial internalization by host cells and the biofilm formation. In this study, we studied different clinical strains of C. acnes. We noticed that C. acnes isolated from PJIs form 2 fold-more biofilm than the strains isolated from a normal skin in two models (Crystal violet staining and fluorescent microscopy (p=0.04 and p=0.02, respectively, Mann-Whitney test). We did not observe any difference in the internalization rate of those strains by osteoblasts. However, the quantity of biofilm formed by C. acnes before and after the internalization was compared. A significant increase in biofilm formation was observed for the strains isolated from the skin (x2.3±0.07; p=0.008, Mann-Whitney test). However, the hydrophobicity of the skin strains is significantly less important than for the PJIs strains (24.8±13% vs 56.6±12% respectively; p=0.003, Mann-Whitney test) but this did not change after internalization suggesting that there is no cell wall evolution. In conclusion, we studied for the first time the impact of bacterial internalization by osteoblasts on the virulent behaviour of C. acnes, which could explain the hided pathogenicity of this commensal bacterium

A substantial body of evidence supports the use of extracorporeal shock wave therapy (ESWT) for fracture non-unions in human medicine. However, the success rate (i.e., radiographic union at six months after ESWT) is only approximately 75%. Detailed knowledge regarding the underlying mechanisms that induce bio-calcification after ESWT is limited. The aim of the present study was to analyse the biological response within mineralized tissue of a new invertebrate model organism, the zebra mussel Dreissena polymorpha, after exposure with extracorporeal shock waves (ESWs). Mussels were exposed to ESWs with positive energy density of 0.4 mJ/mm. 2. or were sham exposed. Detection of newly calcified tissue was performed by concomitantly exposing the mussels to fluorescent markers. Two weeks later, the fluorescence signal intensity of the valves was measured. Mussels exposed to ESWs showed a statistically significantly higher mean fluorescence signal intensity within the shell zone than mussels that were sham exposed. Additional acoustic measurements revealed that the increased mean fluorescence signal intensity within the shell of those mussels that were exposed to ESWs was independent of the size and position of the focal point of the ESWs. These data demonstrate that induction of bio-calcification after ESWT may not be restricted to the region of direct energy transfer of ESWs into calcified tissue. The results of the present study are of relevance for better understanding of the molecular and cellular mechanisms that induce formation of new mineralized tissue after ESWT. Specifically, bio-calcification following ESWT may extend beyond the direct area of treatment

Patients with knee prosthetic joint infection (PJI) frequently receive one- or two-stage revision. To explore the feasibility of a randomised controlled trial (RCT) comparing methods, we analysed a UK registry, interviewed patients and surgeons, systematically reviewed literature, held a consensus meeting, and assessed progress of an RCT in hip PJI. In 2014, in England and Wales, knee PJI was treated with one- or two-stage procedures in 19% and 71% of patients respectively. Between 2007 and 2014, use of one-stage procedures doubled and, in major centres, up to 42% of treatments were one-stage. We conducted in-depth interviews with 16 patients with knee PJI and 11 surgeons performing one- or two-stage revision. Patients considered randomisation acceptable with appropriate counselling and, depending on infecting organisms and health status, surgeons would randomise treatments. In meta-analysis, two-year re-infection rates in 10 one-stage series (423 patients) and 108 two-stage series (5,129 patients) were 7.6% (95%CI 3.4,13.1) and 8.8% (7.2,10.6) respectively. In a series of patients with knee PJI, surgeons from 2 major centres considered 6/15 patients eligible for either treatment, with 4 more potentially eligible after treatment of soft tissue infection. In an ongoing RCT of surgical treatment of hip PJI, 116 patients have been randomised at 14 centres in 3 years. Randomising patients with PJI is feasible but, as knee PJI is uncommon, a multicentre RCT would be required. Based on WOMAC score outcome and appropriate assumptions on eligibility and acceptability, 170 patients would need to be randomised over 4 years at 14 major centres

Infection rates following arthroplasty surgery are between 1–4%, with higher rates in revision surgery. The associated costs of treating infected arthroplasty cases are considerable, with significantly worse functional outcomes reported. New methods of infection prevention are required. HINS-light is a novel blue light inactivation technology which kills bacteria through a photodynamic process. The aim of this study was to investigate the efficacy of HINS-light for the inactivation of bacteria isolated from infected arthoplasty cases. Specimens from hip and knee arthroplasty infections are routinely collected to identify causative organisms. This study tested a range of these isolates for sensitivity to HINS-light. During testing, bacterial suspensions were exposed to increasing doses of HINS-light of (123mW/cm. 2. irradiance). Non-light exposed control samples were also set-up. Bacterial samples were then plated onto agar plates and incubated at 37°C for 24 hours before enumeration. Complete inactivation was achieved for all Gram positive and negative microorganisms. More than a 4-log reduction in Staphylococcus epidermidis and Staphylococcus aureus populations were achieved after exposure to HINS-light for doses of 48 and 55 J/cm. 2. , respectively. Current investigations using Escherichia coli and Klebsiella pneumoniae show that gram-negative organisms are also susceptible, though higher doses are required. This study has demonstrated that HINS-light successfully inactivated all clinical isolates from infected arthroplasty cases. As HINS-light utilises visible-light wavelengths it can be safely used in the presence of patients and staff. This unique feature could lead to possible applications such as use as an infection prevention tool during surgery and post-operative dressing changes

Deep infection represents one of the most devastating complications of total knee arthroplasty. Commonly implicated organisms are gram positive bacteria such as staphylococcus aureus, staphylococcus epidermidis and group B streptococcus. Occasionally, infection may be caused by rare organisms, particularly in the immunocompromised host. We present a case of infected total knee arthroplasty in a penicillin allergic patient, caused by Pasteurella multocida, 13 weeks after the initial surgery. This was treated by open debridement and change of insert as well as aggressive antibiotic therapy. The patient admitted contact with a cat and three dogs at home. Pasteurella multocida is a facultatively anaerobic gram negative coccobacillus. It is a commensal in the nasopharygeal tract of domestic pets such as cats and dogs. Human infection can often be attributed to a bite or scratch. Prosthetic joint infection caused by Pasteurella is uncommon. Only a few cases have been reported in the literature. Our case has several learning points: (1) It is very important to definitively identify Pasteurella because standard therapy for prosthetic joint infection (e.g. flucloxacillin or vancomycin) is not optimal for this species.(2) Pasteurella are susceptible to penicillin, but the optimal antibiotic therapy for infections in patients allergic to beta lactam antibiotics is uncertain. A combination of ciprofloxacin and linezolid is recommended. (3) There is no consensus regarding appropriate management. There are reports of washout and antibiotic therapy alone, single and two stage revision procedures. In our case, at five months follow up, open debridement and change of insert along with antibiotic treatment appears to have been effective, although more long term follow up is required. (4)Post arthroplasty, all patients with pets at home should be advised to seek medical attention following any bite or scratch so that timely prophylaxis can be administered before sepsis becomes deep-seated

We studied the effects of coating titanium implants with teicoplanin and clindamycin in 30 New Zealand White rabbits which were randomly assigned to three groups. The intramedullary canal of the left tibia of each rabbit was inoculated with 500 colony forming units of Staphylococcus aureus. Teicoplanin-coated implants were implanted into rabbits in group 1, clindamycin-coated implants into rabbits in group 2, and uncoated implants into those in group 3. All the rabbits were killed one week later. The implants were removed and cultured together with pieces of tibial bone and wound swabs. The rate of colonisation of the organisms in the three groups was compared. Organisms were cultured from no rabbits in group 1, one in group 2 but from all in group 3. There was no significant difference between groups 1 and 2 (p = 1.000). There were significant differences between groups 1 and 3 and groups 2 and 3 (p < 0.001). Significant protection against bacterial colonisation and infection was found with teicoplanin- and clindamycin-coated implants in this experimental model

Cell-based tissue engineering strategies for tendon repair have limited clinical applicability due to delayed extracellular matrix (ECM) deposition and subsequent prolonged culture periods, which lead to tenogenic phenotypic drift. Deposition of ECM in vitro can be enhanced by macromolecular crowding (MMC), a biophysical phenomenon that governs the intra- and extra-cellular milieu of multicellular organisms, which has been described to accelerate ECM deposition in human tenocytes. A variety of cell sources have been studied for tendon repair including tenocytes, dermal fibroblasts (DFs) and mesenchymal stem cells (MSCs) and various biophysical, biochemical and biological tools have been used to mimic tendon microenvironment. Therefore, we propose to assess the combined effect of MMC and mechanical loading on different cell sources to determine their suitability for the in vitro fabrication of tendon-like tissue. The uniaxial strain induced differential cell orientation based on the differentiation state of the cells: tenocytes and DFs, both permanently differentiated cells exhibited alignment perpendicular to the direction of the load, similarly to what is seen in native tendon environment. Immunocytochemistry showed that, when MMC is used, the DFs and MSCs showed increased deposition of collagen type I, one of the main components in tendon ECM. It is also seen that the ECM deposited follows the alignment of the cell cytoskeleton. However, for tenocytes, deposition of collagen type I is only seen when MMC is used in combination with mechanical loading, indicating that mechanical loading led to increased synthesis of collagen I, suggesting maintenance of the tenogenic phenotype. Other collagen types relevant to native tendon composition were also analysed, including types III, V and VI, and their deposition was also shown to be modulated by the use of MMC and mechanical loading. This appears to recreate the events of tendon tissue formation during development, where these collagen types are involved in regulation of collagen I fibrillogenesis and fibril diameter. Preliminary data also indicates that, under mechanical loading and MMC, expression of tenogenic genes is upregulated whilst chondrogenic and osteogenic markers are downregulated. This indicates the suitability of the combination of MMC and mechanical stimulation for modulating tenogenic phenotype of various cell sources and fabricating tendon-like tissue