Introduction. As new innovations are developed to improve the longevity of joint replacement components, preclinical testing is necessary in the early stages of research into areas such as osseointegration, metal-cartilage wear and periprosthetic joint infection (PJI). Large-animal studies that test load-bearing components are expensive, however, requiring that animals be housed in special facilities that are not available at all institutions. Comparably, small animal models, such as the rat, offer several advantages including lower cost. Load-bearing implants remain difficult to manufacture via traditional methods in the sizes required for small-animal testing. Recent advances in additive manufacturing (3D metal-printing) have allowed for the creation of miniature joint replacement components in a variety of medical-grade metal alloys. The objective of this work is to create and optimize an image-based 3D-printed rat hip implant system that will allow in vivo testing of functional implant properties in a rat model. Methods. A database of n=25 previously-acquired, 154μm micro-CT volumes (eXplore Locus Ultra, GE Medical) of male Sprague-Dawley rats (390–610g) were analyzed to obtain spatial and angular relationships between several anatomical features of the proximal rat femora. Mean measurements were used to guide the creation of a femoral implant template in computer-aided design software (Solidworks, Dassault Systemes). Several different variations were created, including collarless and collared designs, in a range of sizes to accommodate rats of various weights. Initial prototypes were 3D-printed 316L stainless steel with subsequent iterations printed in Ti6Al4V titanium and F75 cobalt-chrome. Implants were post-processed via sandblasting, hand-polishing, ultrasonic bath, and sterilization in an autoclave. Innate surface texturing was left on manufactured stems to promote osseointegration. Surgical implantation was performed in three live Sprague-Dawley rats (900g, 500g, 750g) with preservation of muscle attachments to the greater trochanter. Micro-CT imaging and X-ray fluoroscopy were performed post-operatively on each animal at 1 day, and 1, 3, 9 and 12 weeks to evaluate gait and component positioning. Results. Implantation of components was successful and each animal was observed to ambulate on its affected limb immediately following recovery from surgery. The 900g rat, given a collarless 316L stainless steel component, was kept for 11 months post-implantation before succumbing to old age. Micro-CT and fluoroscopic findings revealed no evidence of implant subsidence. The 500g animal, given a collarless 316L stainless steel implant, showed evidence of implant subsidence at 3 weeks, with full subsidence and hip dislocation at 12 weeks. The 750g rat, given a collared F75 cobalt-chrome implant, was observed ambulating on its affected limb, but experienced implant rotation and failure at 9 weeks. Conclusions. We report the first hip hemi-arthroplasty in a rat using a 3D-printed metal implant. This model aims to provide a low-cost platform for studying osseointegration, metal-cartilage interactions, and PJI using a functional, loaded implant. Efforts to further optimize the surgical approach will be made to reduce early implant loosening. A study with larger sample sizes is needed to determine if implants can be installed repeatedly, without complications, before the utility of this approach can be validated. Future work will include surface preparations on implant stems, with micro-CT to longitudinally track changes at the bone-metal interface, and gait analysis on a radiolucent treadmill to quantify post-operative kinematics

We created TiO. 2. nanotubes (TNTs) on the surface of titanium (Ti) implants with subsequential loading with gentamicin and chitosan, acting as a control release agent, by electrophoretic deposition (EPD). We hypothesized femoral implants with TNTs loaded with gentamicin and chitosan would localize antibiotic to the implant and surgical site and prevent PJI in a mouse model. Ti-6Al-4V ELI wires underwent TNT surface modification by two-step anodization. EPD was then used to load gentamicin and chitosan onto the Ti wire with surface TNTs. Control Ti wires contained TNTs with EPD of chitosan only. 12-week-old male C57BL/6J mice underwent received a right femoral intramedullary implant followed by inoculation at the surgical site with 1×10. 3. CFUs of bioluminescent Xen36 Staphylococcus aureus (S. aureus). Mice were randomly divided into two implant groups: 1) Gentamicin + Chitosan Group (n=7; experimental group); 2) Chitosan Group (n=7; control group). Outcomes included: 1) Relative S. aureus abundance by bioluminescence imaging; 2) Quantification of S. aureus at the implant and surrounding tissue by colony forming unit (CFU) analysis; 3) Scanning electron microscopy (SEM) for implant bacterial biofilm; 4) Radiographic signs of PJI. Over 14 days assessment following wire implantation and inoculation with S. aureus, the experimental group had no evidence of infection based on i) no increased Xen36 S. aureus bioluminescence signal and ii) no CFUs present. All control had increased bioluminescence signal, above baseline, at all time-points and presence of CFUs. Ti femoral implants modified with surface TNTs and coated with gentamicin and chitosan through EPD prevented PJI in all mice through 14 days. In comparison, all control mice demonstrated evidence of PJI over 14 days. Implants with TNTs and EPD of gentamicin were highly effective in this mouse PJI model

Aims

The aims of this study were to determine the incidence and factors for developing periprosthetic joint infection (PJI) following hemiarthroplasty (HA) for hip fracture, and to evaluate treatment outcome and identify factors associated with treatment outcome.

Introduction. We studied free (= local powder) tobramycin and doxycycline, and controlled release (= local lipid bilayer) doxycycline formulations in a rat model representing a generic joint infection. We . hypothesized. that evidence of infection (quantitative colony forming units (CFU), qualitative SEM, histopathology) (1a) would be reduced with local vs. systemic antibiotic, (1b) any antibiotic would be superior to control (2) there would be a difference among antibiotics, and (3) antibiotic would not be detectable in serum at 4-week euthanasia. Methods. Study groups. included infected and non-infected (1) control, (2) systemic ceftriaxone (daily), (3) local tobramycin, (4) local doxycycline and (5) controlled release doxycycline. With IACUC approval, (10 rats/group; power =0.8), 50-μl, 10×4 CFU Staphylococcus aureus, slowly injecting into distal femoral medullary canal, reliably created joint infection. Antibiotic formulation was introduced locally into cavity and joint, pin was inserted, and tissues closed. After 4-weeks, serum, pin, bone and synovium were obtained. CFU/ml of bone and synovium were quantified using macrotiter method. SEM imaged biofilm on surface of pin, histopathology identified tissue response, liquid chromatography/mass spectrometry measured plasma antibiotic. Kruskal-Wallis one-way ANOVA compared groups. Results. Groups receiving antibiotic reported lower CFU/ml in synovium compared with control (no treatment) group (1b), but there was no difference between systemic, free or controlled antibiotics (1a). Different results with different antibiotics were shown, with free tobramycin reducing CFU/ml to a greater extent than free doxycycline in the synovium (2) (p<0.05). Antibiotic in plasma was nondetectable all groups (3). SEM revealed some biofilm on pin in all groups. . Limitations. include inoculation method, single observation period, administration of only one bacterial and antibiotic dose, and not including pairing local and systemic antibiotic. Conclusion. There was no difference in infection reduction nor detectable antibiotic in serum for any antibiotic formulation, but CFU's in synovium differed based on antibiotic formulation. For any tables or figures, please contact the authors directly

Aims

Aseptic loosening is a leading cause of uncemented arthroplasty failure, often accompanied by fibrotic tissue at the bone-implant interface. A biological target, neutrophil extracellular traps (NETs), was investigated as a crucial connection between the innate immune system’s response to injury, fibrotic tissue development, and proper bone healing. Prevalence of NETs in peri-implant fibrotic tissue from aseptic loosening patients was assessed. A murine model of osseointegration failure was used to test the hypothesis that inhibition (through Pad4^-/- mice that display defects in peptidyl arginine deiminase 4 (PAD4), an essential protein required for NETs) or resolution (via DNase 1 treatment, an enzyme that degrades the cytotoxic DNA matrix) of NETs can prevent osseointegration failure and formation of peri-implant fibrotic tissue.

Aims

Interleukin (IL)-1β is one of the major pathogenic regulators during the pathological development of intervertebral disc degeneration (IDD). However, effective treatment options for IDD are limited. Suramin is used to treat African sleeping sickness. This study aimed to investigate the pharmacological effects of suramin on mitigating IDD and to characterize the underlying mechanism.

Bone ingrowth is desired with uncemented hip implants. Infection is clearly undesirable. We have worked on developing a nanofiber coating for implants that would enhance bone formation while inhibiting infection. Few studies have focused on developing an implant surface nanofiber (NF) coating to prevent infection and enhance osseointegration by local drug release. In this study, coaxial doxycycline (Doxy)-doped polycaprolactone/polyvinyl alcohol (PCL/PVA) Nanofibers were directly deposited on the titanium (Ti) implant surface during electrospinning. The interaction of loaded Doxy with both PVA and PCL NFs was characterized by Raman spectroscopy. The bonding strength of Doxy-doped NF coating on Ti implants was confirmed by a stand single-pass scratch test. The improved implant osseointegration by PCL/PVA NF coatings in vivo was confirmed by scanning electron microscopy, histomorphometry and micro computed tomography at 2, 4 and 8 weeks after implantation. The bone contact surface (%) changes of NF coating group (80%) is significantly higher than that of no NF group (< 5%, p<0.05). Finally, we demonstrated that Doxy-doped NF coating effectively inhibited bacterial infection and enhanced osseointegration in an infected (Staphylococcus aureus) tibia implantation rat model. Doxy released from NF coating inhibited bacterial growth up to 8 weeks in vivo. The maximal push-in force of Doxy-NF coating (38 N) is much higher than that of NF coating group (6.5 N) 8 weeks after implantation (p<0.05), which was further confirmed by quantitative histological analysis and micro computed tomography. These findings indicate that coaxial PCL/PVA NF coating doped with Doxy and/or other drugs have great potential in enhancing implant osseointegration and preventing infection

Aims

The aims of this study were to develop an in vivo model of periprosthetic joint infection (PJI) in cemented hip hemiarthroplasty, and to monitor infection and biofilm formation in real-time.

Aims

To evaluate the effect of ultrasound-targeted simvastatin-loaded microbubble destruction (UTMD_SV) for alleviation of the progression of osteoarthritis (OA) in rabbits through modulation of the peroxisome proliferator-activated receptor (PPARγ).

Aims

The processes linking long-term bisphosphonate treatment to atypical fracture remain elusive. To establish a means of exploring this link, we have examined how long-term bisphosphonate treatment with prior ovariectomy modifies femur fracture behaviour and tibia mass and shape in murine bones.

Objectives

The primary purpose of this meta-analysis was to determine whether statin usage could reduce the risk of glucocorticoid-related osteonecrosis in animal models.

We measured the plasma 25-hydroxyvitamin D₃ (25(OH)D₃) levels in 62 consecutive Caucasian patients undergoing total hip replacement for osteoarthritis. The patients were divided into two groups based on whether they were vitamin D sufficient or deficient. The groups were matched for age, gender and the American Society of Anaesthesiologists (ASA) grade. The prevalence of vitamin D deficiency in our patients was comparable with recent population-based studies performed in the United Kingdom. Patients with vitamin D deficiency had lower pre-operative Harris hip scores (Mann-Whitney test, p = 0.018) and were significantly less likely to attain an excellent outcome from total hip replacement (chi-squared test, p = 0.038). Vitamin D levels were found to positively correlate with both pre- and post-operative Harris hip scores.

These results warrant further study of vitamin D deficiency in patients undergoing joint replacement as it is a risk factor for a suboptimal outcome which is relatively simple and cheap to correct.

We examined whether a selective cyclooxygenase-2 (COX-2) inhibitor (celecoxib) was as effective as a non-selective inhibitor (ibuprofen) for the prevention of heterotopic ossification following total hip replacement. A total of 250 patients were randomised to receive celecoxib (200 mg b/d) or ibuprofen (400 mg t.d.s) for ten days after surgery. Anteroposterior radiographs of the pelvis were examined for heterotopic ossification three months after surgery. Of the 250 patients, 240 were available for assessment. Heterotopic ossification was more common in the ibuprofen group (none 40.7% (50), Brooker class I 46.3% (57), classes II and III 13.0% (16)) than in the celecoxib group (none 59.0% (69), Brooker class I 35.9% (42), classes II and III 5.1% (6), p = 0.002). Celecoxib was more effective than ibuprofen in preventing heterotopic bone formation after total hip replacement.

Bisphosphonates reduce peri-prosthetic bone loss in the short term after total hip replacement but the mid- and longer term effects are not known. The aims of this randomised trial were to examine the effect of a single dose of 90 mg of pamidronate on the clinical and radiological outcome and peri-prosthetic bone mineral density in 50 patients (56 hips) over a five-year period, following total hip replacement.

At five years, 37 patients (42 hips) returned for assessment. The Harris hip scores were similar in the pamidronate and placebo groups throughout the study. Also at five years, four patients, two from each group had osteolytic lesions on plain radiography. These were located around the acetabular component in three patients and in the femoral calcar in one. The femoral and acetabular peri-prosthetic bone mineral density in the pamidronate group and the control group was similar at five years.

Pamidronate given as a single post-operative dose does not appear to influence the clinical outcome or prevent the development of osteolytic lesions at five years after total hip replacement.