Osteoarthritis (OA) is the most common type of arthritis and causes a significant deterioration in patients’ quality of life. The high prevalence of OA as well as the current lack of disease-modifying drugs led to a rise in regenerative medicine efforts. The hope is that this will provide a treatment modality with the ability to alter the course of OA via structural modifications of damaged articular cartilage (AC). Regenerative therapy in OA starts with the concept that administered cells may engraft to a lesion site and differentiate into chondrocytes. However, recent studies show that cells, particularly when injected in suspension, rapidly undergo apoptosis after exerting a transient paracrine effect. If the injected stem cells do not lead to structural improvements of a diseased joint, the high cost of cell therapy for OA cannot be justified, particularly when compared with other injection therapeutics such as corticosteroids and hyaluronic acid. Long-term survival of implanted cells that offer prolonged paracrine effects or possible engraftment is essential for a successful cell therapy that will offer durable structural improvements. In this talk, the history and current status of regenerative therapy in OA are summarized along with the conceptual strategy and future directionsfor a successful regenerative therapy that can provide structural modifications in OA

Introduction and Objective. TKA have shown both excellent long-term survival rate and symptoms and knee function improvement. Despite the good results, the literature reports dissatisfaction rates around 20%. This rate of dissatisfaction could be due to the overstuff that mechanically aligned prostheses could produce during the range of motion. Either size discrepancy between bone resection and prosthetic component and constitutional mechanical tibiofemoral alignment (MTFA) alteration might increase soft tissue tension within the joint, inducing pain and functional limitation. Materials and Methods. Total knee arthroplasties performed between July 2019 and September 2020 were examined and then divided into two groups based on the presence (Group A) or absence (Group B) of patellofemoral overstuff, defined as a thickness difference of more than 2 mm between chosen component and bone resection performed, taking into account at least one of the following: femoral medial and lateral condyle, medial or lateral trochlea and patella. Based on pre and post-operative MTFA measurements, Group A was further divided into two subgroups whether the considered alignment was modified or not. Patients were assessed pre-operatively and at 6 months post-op using the Knee Society Score (KSS), Oxford Knee Score (OKS), Forgotten Joint Score (FJS), Visual Analogue Scale (VAS) and Range of Motion (ROM). Results. One hundred total knee arthroplasties were included in the present study, 69 in Group A and 31 in group B. Mean age and BMI of patients was respectively 71 and 29.2. The greatest percentage of Patellofemoral Overstuff was found at the distal lateral femoral condyle. OKS, KSS functional score, and FJS were statistically significant higher in patients without Patellofemoral Overstuff. Therefore, Group A patients with a non-modified MTFA demonstrated statistically significant better KSS, ROM and FJS. Conclusions. Patellofemoral Overstuff decrease post-operative clinical scores in patients treated with TKA. The conventional mechanically aligned positioning of TKA components might be the primary cause of prosthetic overstuffing leading to worsened clinical results. Level of evidence: III; Prospective Cohort Observational study;

Long-term survival and favourable outcome of implant use are determined by bone-implant osseointegration and absence of infection near the implants. As with most diseases, prevention is the preferred approach. Silver ion doped calcium phosphate based ceramic coating (Silveron®) for implant coating has been shown previously to be a potent antimicrobial agent as indicated by in vitro testing. The present study reports on clinical experience using silver ion doped calcium phosphate based ceramic coated external fixator pins as surgical treatment in the management of chronic osteomyelitis and open fractures. Ten patients had external fixators: six for open fractures of ankle, three for chronic osteomyelitis of the femur, one for tibia pseudoarthrosis. The electrospray method was used for coating the external fixator pins with silver ion doped calcium phosphate-based ceramics. A radiofrequency energy source was used to sinter the coated pins. Microbiological, roentgenographic, toxic and biochemical analyzes of patients were carried out. Wound debridement, and subsequent wound care resulted in control of the infection in three chronic osteomyelitis and in healing of seven fractures after follow-up ranging from three to six months. In total 67 pins were used in 10 patients but only one pin was positive microbiologically in one patient. Collectively, these data clearly illustrate that the toxic effects of silver were not observed at the doses used. Silver ion doped calcium phosphate based ceramic coating (Silveron®) can be used to prevent infection associated with the implant

Long-term survival of massive prostheses used to treat bone cancers is associated with extra-cortical bone growth and osteointegration into a grooved hydroxyapatite coated collar positioned adjacent to the transection site on the implant shaft [1]. The survivorship at 10 years reduces from 98% to 75% where osteointegration of the shaft does not occur. Although current finite element (FE) methods successfully model bone adaption, optimisation of adventitious new bone growth and osteointegration is difficult to predict. There is thus a need to improve existing FE models by including biological processes of osteoconduction and osteoinduction. The principal bone adaptation criteria is based on the standard strain-energy remodeling algorithm, where the rate of remodeling is controlled by the difference in the stimulus against the reference value [3]. The additional concept of bone connectivity was introduced, to limit bone growth to neighbouring elements (cells) adjoining existing bone elements. The algorithm was developed on a cylindrical model before it was used on an ovine model. The geometry and material properties from two ovine tibiae were obtained from computed tomography (CT) scans and used to develop FE models of the tibiae implanted with a grooved collar. The bones were assigned inhomogeneous material properties based on the CT grey values and typical ovine walking load conditions were applied. The FE results show a region of bone tissue growth below the implanted collar and a small amount of osteointegration with the implant, which is in good agreement to clinical results. Some histological results suggest that further bone growth is possible and potential improvements to the model will be discussed. In summary, by including an algorithm that describes osteoconduction, adventitious bone growth can be predicted

Osteoarthritis (OA) is an inflammatory degenerative disease that affects every fourth person with irreversible damage to the articular. Mesenchymal stem cells (MSCs) have been shown to affect host cells by paracrine stimulation in regenerative environments. Here we apply hyaluronic acid (HA), an essential part of the extracellular matrix in cartilage, for MSC immobilization. The aim was to investigate long-term MSC survival and paracrine effect on chondrocytes in an inflammatory co-culture environment. We hypothesized that MSCs immobilized in a HA hydrogel could provide a long-term immunomodulatory effect on chondrocytes in vitro. Human MSCs were seeded in a HA hydrogel and co-cultured with non-osteoarthritic human chondrocytes in biphasic wells inhibiting cellular contact. An inflammatory environment was induced by IL1-beta and compared with standard culture medium. Relative gene expressions of collagen types I, II and X, aggrecan, SOX9, MMP-13 and ADAMTS-5) were examined at day 3,7,14 and 28. Significant up-regulation of SOX9 at day 7, 14 and 28 and a significant down-regulation of ADAMTS-5 (day 14 and 28) was observed with co-culture of HA-immobilized MSCs and MSCs compared with controls with or without HA (without MSCs)No changes in expression was observed for aggrecan and collagen type 1. We showed that MSC affect the expression of SOX9 and ADAMTS-5 in a paracrine manner when co-cultured with chondrocytes in an inflammatory environment. MSCs immobilized in HA hydrogels survived and were contained in the hydrogel for up to 28 days. This suggests that HA-immobilized MSCs could potentially be used as adjuvant treatment of OA

Background. Implant stability and is an important factor for adequate bone remodelling and both are crucial in the long-term clinical survival of total hip arthroplasty (THA). Assessment of early bone remodelling on X-rays during the first 2 years post-operatively is mandatory when stepwise introduction of a new implant is performed. Regardless of fixation type (cemented or cementless), early acetabular component migration is usually the weakest link in THA, eventually leading to loosening. Over the past years, a shift towards uncemented cup designs has occurred. Besides the established hydroxyapatite (HA) coated uncemented cups which provide ongrowth of bone, new uncemented implant designs stimulating ingrowth of bone have increased in popularity. These cups initiate ingrowth of bone into the implant by their open metallic structure with peripheral pores, to obtain a mechanical interlock with the surrounding bone, thereby stabilising the prosthesis in an early stage after implantation. This retrospective study assessed bone remodelling, osseointegration and occurrence of radiolucency around a new ingrowth philosophy acetabular implant. Methods. In a retrospectively, single centre cohort study all patients whom underwent primary THA with a Tritanium acetabular component in 2011 were included. Bone remodelling, osseointegration and occurrence of radiolucency were determined by two reviewers from X-ray images that were made at 6 weeks, 3–6-12 and 24 months post-operatively. Bone contact % was calculated based on the original Charnley and DeLee zones. According to Charnley and DeLee the outer surface of an acetabular cup is divided into 3 zones (1-2-3). For our analysis the original 3 zones were further divided into 2 producing 6 zones 1A to 3B. Each of these 6 zones were then further divided into 4 equal sections. We attributed 25 points per section in which complete bone contact without lucency was observed. If lucency was observed no points were attributed to the section. A fully osteointegrated cup in all 24 sections could therefore attain 600 points. The total of each section and zone was subsequently tallied and recalculated to produce the percentage of bone contact on a 1–100% score. Results. In 2011 131 patients; 54 male and 76 female with average age of 60.83 (SD 12.42) and 60.57 (SD 12.11) year respectively underwent primary THA at our institution and all where included in our study cohort. Majority of this cohort underwent primary THA due to osteoarthrosis and most patients were classified ASO I (18%) or ASA II (65%). At two year clinical follow-up two revision were performed. One constituted a femur and acetabulum revision due to leg length difference and a snapping hip phenomenon. Complications included 3 dislocations (all treated policlinic), 4 deep infections (all treated with Genta PMMA beads with prosthesis in situ and healed) and 1 removal of hematoma. In another patient the femoral component was revised due to a peri-prosthetic fracture. Mean bone contact % values for all Charnley and DeLee zones combined were calculated and improved from 68,18% (SD 22,36) at 6 weeks to 73,61% SD (16,26) at 3 months to 84,21% (SD 19,02) at 6 months to 86,90% (SD 16,0) at 1 year to 92,19% (SD 12,74) at two year follow-up. When analysing the bone contact % per individual zone a remarkable difference was found for zones 2A-B. In contrast to zone 1A-B and 3A-B the initial bone contact % was clearly although not significantly lower until two year follow-up. Conclusions. In this study, the bone apposition around Tritanium actebular component was retrospectively assessed until two year clinical. Our results show excellent bone apposition that continues to improve over time (at least until two year clinical follow-up) suggesting that the open trabecular Ti structure of the Tritanium has a positive effect on cup osseointegration. However, some recent reports have shown the development of reactive lines around cups with porous/trabecular metal surfaces, of which the meaning is still unclear. Our analysis indicated that especially acetabular zone 2A-B according to Charnley&DeLee needs time to establish a direct contact of the implant surface and the surrounding bone tissues. Perhaps this might be explained by reaming technique (underreaming vs line to line reaming) resulting in suboptimal seating of the cup. Therefore, careful follow-up of this new implant technology will remain necessary and continued in this study. We aim to improve cohort size and establish results at longer follow-up times. Furthermore we aim to correlate these results to RSA component migration analysis

Currently, there are no generally accepted treatments for the prevention of osteonecrosis. To compound this further, despite considerable research efforts, the natural history of this disease remains poorly understood. The disease process appears to be initially asymptomatic, but after symptoms appear, the course becomes rapidly progressive. Clinical studies have shown that, if left untreated, collapse of the femoral head will occur in 80 per cent of the cases or greater within four years. As our knowledge of the etiology and pathogenesis of osteonecrosis improves, new treatments to halt, or at least impede, the progression of the disease may be possible. Achieving the best outcomes in the treatment of osteonecrosis depends on early, accurate diagnosis, and prompt treatment appropriate for the stage of the disease. In many cases, if treated early, long-term preservation of the native joint is possible. Magnetic resonance imaging allows accurate diagnosis in even the earliest asymptomatic stages of the disease. Non-surgical treatments such as pharmacological agents have shown promise in experimental studies, although further work remains before they are appropriate for widespread use. Various hip salvaging procedures such as core decompression, percutaneous drilling, non-vascularized and vascularized bone grafting, and various osteotomies have been successful in the majority of properly selected patients over follow-up times of a decade or more. Advances in arthroplasty technologies and techniques, including hip resurfacing and modern cementless total hip arthroplasty have allowed patients to return to pain-free, active lifestyles with excellent long-term prosthesis survival. Current treatments for osteonecrosis, while generally successful, focus on halting or delaying the progression of symptomatic disease. Recent discoveries concerning the relationship between genetic factors and the development of osteonecrosis, as well as the pathophysiologic effects of various indirect and direct risk factors such as corticosteroid use and sickle cell disease, continue to improve our understanding of the underlying disease process. While these discoveries are promising, we must continue to work towards the goal of being able to identify and treat the precursors of osteonecrosis before it progresses to symptomatic disease and threatens the survival of native joints

Impaction allograft is an established method of securing initial stability of an implant in arthroplasty. Subsequent bone integration can be prolonged, and the volume of allograft may not be maintained. Intermittent administration of parathyroid hormone has an anabolic effect on bone and may therefore improve integration of an implant.

Using a canine implant model we tested the hypothesis that administration of parathyroid hormone may improve osseointegration of implants surrounded by bone graft. In 20 dogs a cylindrical porous-coated titanium alloy implant was inserted into normal cancellous bone in the proximal humerus and surrounded by a circumferential gap of 2.5 mm. Morsellised allograft was impacted around the implant. Half of the animals were given daily injections of human parathyroid hormone (1–34) 5 μg/kg for four weeks and half received control injections. The two groups were compared by mechanical testing and histomorphometry. We observed a significant increase in new bone formation within the bone graft in the parathyroid hormone group. There were no significant differences in the volume of allograft, bone-implant contact or in the mechanical parameters.

These findings suggest that parathyroid hormone improves new bone formation in impacted morsellised allograft around an implant and retains the graft volume without significant resorption. Fixation of the implant was neither improved nor compromised at the final follow-up of four weeks.

Malrotation of the femoral component is a cause of patellofemoral maltracking after total knee arthroplasty. Its precise effect on the patellofemoral mechanics has not been well quantified. We have developed an in vitro method to measure the influence of patellar maltracking on contact. Maltracking was induced by progressively rotating the femoral component either internally or externally. The contact mechanics were analysed using Tekscan. The results showed that excessive malrotation of the femoral component, both internally and externally, had a significant influence on the mechanics of contact. The contact area decreased with progressive maltracking, with a concomitant increase in contact pressure. The amount of contact area that carries more than the yield stress of ultra-high molecular weight polyethylene significantly increases with progressive maltracking. It is likely that the elevated pressures noted in malrotation could cause accelerated and excessive wear of the patellar button.

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.

We investigated the effect of pre-heating a femoral component on the porosity and strength of bone cement, with or without vacuum mixing used for total hip replacement.

Cement mantles were moulded in a manner simulating clinical practice for cemented hip replacement. During polymerisation, the temperature was monitored. Specimens of cement extracted from the mantles underwent bending or fatigue tests, and were examined for porosity.

Pre-heating the stem alone significantly increased the mean temperature values measured within the mantle (+14.2°C) (p < 0.001) and reduced the mean curing time (−1.5 min) (p < 0.001). The addition of vacuum mixing modulated the mean rise in the temperature of polymerisation to 11°C and reduced the mean duration of the process by one minute and 50 seconds (p = 0.01 and p < 0.001, respectively). In all cases, the maximum temperature values measured in the mould simulating the femur were < 50°C. The mixing technique and pre-heating the stem slightly increased the static mechanical strength of bone cement. However, the fatigue life of the cement was improved by both vacuum mixing and pre-heating the stem, but was most marked (+ 280°C) when these methods were combined.

Pre-heating the stem appears to be an effective way of improving the quality of the cement mantle, which might enhance the long-term performance of bone cement, especially when combined with vacuum mixing.

In order to investigate the osteoinductive properties of allograft used in impaction grafting and the effect of strain during impaction on these properties, we designed an in vitro experiment to measure strain-related release of bone morphogenetic protein-7 (BMP-7) from fresh-frozen femoral head allograft. A total of 40 10 mm cubes of cancellous bone were cut from ten samples of fresh-frozen femoral head. The marrow was removed from the cubes and the baseline concentrations of BMP-7 were measured. Specimens from each femoral head were allocated to four groups and subjected to different compressive strains with a material testing machine, after which BMP-7 activity was reassessed. It was present in all groups. There was a linear increase of 102.1 pg/g (95% confidence interval 68.6 to 135.6) BMP-7 for each 10% increase in strain. At 80% strain the mean concentration of BMP-7 released (830.3 pg/g bone) was approximately four times that released at 20% strain. Activity of BMP-7 in fresh-frozen allograft has not previously been demonstrated. This study shows that the freezing and storage of femoral heads allows some maintenance of biological activity, and that impaction grafting provides a source of osteoinductive bone for remodelling.

We have shown that BMP-7 is released from fresh-frozen femoral head cancellous bone in proportion to the strain applied to the bone. This suggests that the impaction process itself may contribute to the biological process of remodelling and bony incorporation.

The aim of our study was to investigate whether placing of the femoral component of a hip resurfacing in valgus protected against spontaneous fracture of the femoral neck.

We performed a hip resurfacing in 20 pairs of embalmed femora. The femoral component was implanted at the natural neck-shaft angle in the left femur and with a 10° valgus angle on the right. The bone mineral density of each femur was measured and CT was performed. Each femur was evaluated in a materials testing machine using increasing cyclical loads.

In specimens with good bone quality, the 10° valgus placement of the femoral component had a protective effect against fractures of the femoral neck. An adverse effect was detected in osteoporotic specimens.

When resurfacing the hip a valgus position of the femoral component should be achieved in order to prevent fracture of the femoral neck. Patient selection remains absolutely imperative. In borderline cases, measurement of bone mineral density may be indicated.

Dislocation remains a major concern after total hip replacement, and is often attributed to malposition of the components. The optimum position for placement of the components remains uncertain. We have attempted to identify a relatively safe zone in which movement of the hip will occur without impingement, even if one component is positioned incorrectly. A three-dimensional computer model was designed to simulate impingement and used to examine 125 combinations of positioning of the components in order to allow maximum movement without impingement. Increase in acetabular and/or femoral anteversion allowed greater internal rotation before impingement occurred, but decreases the amount of external rotation. A decrease in abduction of the acetabular components increased internal rotation while decreasing external rotation. Although some correction for malposition was allowable on the opposite side of the joint, extreme degrees could not be corrected because of bony impingement.

We introduce the concept of combined component position, in which anteversion and abduction of the acetabular component, along with femoral anteversion, are all defined as critical elements for stability.

Studies on the migration of an implant may be the only way of monitoring the early performance of metal-on-metal prostheses. The Ein Bild Roentgen Analyse - femoral component analysis (EBRA-FCA) method was adapted to measure migration of the femoral component in a metal-on-metal surface arthroplasty of the hip using standard antero-posterior radiographs. In order to determine the accuracy and precision of this method a prosthesis was implanted into cadaver bones. Eleven series of radiographs were used to perform a zero-migration study. After adjustment of the femoral component to simulate migration of 3 mm the radiographs were repeated. All were measured independently by three different observers.

The accuracy of the method was found to be ± 1.6 mm for the x-direction and ± 2 mm for the y-direction (95% percentile). The method was validated using 28 hips with a minimum follow-up of 3.5 years after arthroplasty. Seventeen were sound, but 11 had failed because of loosening of the femoral component. The normal (control) group had a different pattern of migration compared with that of the loose group. At 29.2 months, the control group showed a mean migration of 1.62 mm and 1.05 mm compared with 4.39 mm and 4.05 mm in the failed group, for the centre of the head and the tip of the stem, respectively (p = 0.001). In the failed group, the mean time to migration greater than 2 mm was earlier than the onset of clinical symptoms or radiological evidence of failure, 19.1 versus 32.2 months (p = 0.001) and 24.8 months (p = 0.012), respectively.

EBRA-FCA is a reliable and valid tool for measuring migration of the femoral component after surface arthroplasty and can be used to predict early failure of the implant. It may be of value in determining the long-term performance of surface arthroplasty.