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. Methods. Sprague-Dawley rats underwent cemented hip hemiarthroplasty via the posterior approach with pre- and postoperative gait assessments. Infection with Staphylococcus aureus Xen36 was monitored with in vivo photoluminescent imaging in real-time. Pre- and postoperative gait analyses were performed and compared. Postmortem micro (m) CT was used to assess implant integration; field emission scanning electron microscopy (FE-SEM) was used to assess biofilm formation on prosthetic surfaces. Results. All animals tolerated surgery well, with preservation of gait mechanics and weightbearing in control individuals. Postoperative in vivo imaging demonstrated predictable evolution of infection with logarithmic signal decay coinciding with abscess formation. Postmortem mCT qualitative volumetric analysis showed high contact area and both cement-bone and cement-implant interdigitation. FE-SEM revealed biofilm formation on the prosthetic head. Conclusion. This study demonstrates the utility of a new, high-fidelity model of in vivo PJI using cemented hip hemiarthroplasty in rats. Inoculation with bioluminescent bacteria allows for non-invasive, real-time monitoring of infection. Cite this article: Bone Joint J 2021;103-B(7 Supple B):9–16

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

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

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Aims

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Aims

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Objectives

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