An understanding of the remodelling of tendon is crucial for the development of scientific methods of treatment and rehabilitation. This study tested the hypothesis that tendon adapts structurally in response to changes in functional loading. A novel model allowed manipulation of the mechanical environment of the patellar tendon in the presence of normal joint movement via the application of an adjustable external fixator mechanism between the patella and the tibia in sheep, while avoiding exposure of the patellar tendon itself. Stress shielding caused a significant reduction in the structural and material properties of stiffness (79%), ultimate load (69%), energy absorbed (61%), elastic modulus (76%) and ultimate stress (72%) of the tendon compared with controls. Compared with the material properties the structural properties exhibited better recovery after re-stressing with stiffness 97%, ultimate load 92%, energy absorbed 96%, elastic modulus 79% and ultimate stress 80%. The cross-sectional area of the re-stressed tendons was significantly greater than that of stress-shielded tendons. The remodelling phenomena exhibited in this study are consistent with a putative feedback mechanism under strain control. This study provides a basis from which to explore the interactions of tendon remodelling and mechanical environment

Aims

Arthroplasty has been shown to generate the most waste among all orthopaedic subspecialties, and it is estimated that hip and knee arthroplasty generate in excess of three million kg of waste annually in the UK. Infectious waste generates up to ten times more CO2 compared with recycled waste, and previous studies have shown that over 90% of waste in the infectious stream is misallocated. We assessed the effect of real-time waste segregation by an unscrubbed team member on waste generation in knee and hip arthroplasty cases, and compared this with a simple educational intervention during the ‘team brief’ at the start of the operating list across two sites.

Little is known about the tissue reactions to various implant materials which coincide with an inflammatory reaction. We used the avridine arthritis rat model to evaluate the tissue response in the synovial, interstitial and subcutaneous tissues after implant insertion.

Quantitative immunohistochemistry showed that normal joint synovial tissue is dominated by ED2-positive resident macrophages. Polyethylene implants induced a much stronger foreign-body reaction than titanium implants, as measured by the number of interfacial ED1-positive macrophages. The tissue response to titanium and polyethylene was also vastly different in arthritic synovial tissue compared with control tissue.

It is likely that these biomaterials interact differently with inflammatory cells or intermediary compounds. It may be that arthritic synovial tissue produces reactive oxygen intermediates (free radicals) with which titanium has a unique anti-inflammatory interaction in vitro.

Rotator cuff tears are common in middle-aged and elderly patients. Despite advances in the surgical repair of rotator cuff tears, the rates of recurrent tear remain high. This may be due to the complexity of the tendons of the rotator cuff, which contributes to an inherently hostile healing environment. During the past 20 years, there has been an increased interest in the use of biologics to complement the healing environment in the shoulder, in order to improve rotator cuff healing and reduce the rate of recurrent tears. The aim of this review is to provide a summary of the current evidence for the use of forms of biological augmentation when repairing rotator cuff tears. Cite this article: Bone Joint J 2024;106-B(9):978–985

Aims. As an increasing number of female surgeons are choosing orthopaedics, it is important to recognize the impact of pregnancy within this cohort. The aim of this review was to examine common themes and data surrounding pregnancy, parenthood, and fertility within orthopaedics. Methods. A systematic review was conducted by searching Medline, Emcare, Embase, PsycINFO, OrthoSearch, and the Cochrane Library in November 2022. The Preferred Reporting Items for Systematic Reviews and Meta Analysis were adhered to. Original research papers that focused on pregnancy and/or parenthood within orthopaedic surgery were included for review. Results. Of 1,205 papers, 19 met the inclusion criteria. Our results found that orthopaedic surgeons have higher reported rates of obstetric complications, congenital abnormalities, and infertility compared to the general population. They were noted to have children at a later age and voluntarily delayed childbearing. Negative perceptions of pregnancy from fellow trainees and programme directors were identified. Conclusion. Female orthopaedic surgeons have high rates of obstetric complications and infertility. Negative perceptions surrounding pregnancy can lead to orthopaedic surgeons voluntarily delaying childbearing. There is a need for a pregnancy-positive culture shift combined with formalized guidelines and female mentorship to create a more supportive environment for pregnancy within orthopaedic surgery. Cite this article: Bone Joint J 2023;105-B(8):857–863

Aims. Several artificial bone grafts have been developed but fail to achieve anticipated osteogenesis due to their insufficient neovascularization capacity and periosteum support. This study aimed to develop a vascularized bone-periosteum construct (VBPC) to provide better angiogenesis and osteogenesis for bone regeneration. Methods. A total of 24 male New Zealand white rabbits were divided into four groups according to the experimental materials. Allogenic adipose-derived mesenchymal stem cells (AMSCs) were cultured and seeded evenly in the collagen/chitosan sheet to form cell sheet as periosteum. Simultaneously, allogenic AMSCs were seeded onto alginate beads and were cultured to differentiate to endothelial-like cells to form vascularized bone construct (VBC). The cell sheet was wrapped onto VBC to create a vascularized bone-periosteum construct (VBPC). Four different experimental materials – acellular construct, VBC, non-vascularized bone-periosteum construct, and VBPC – were then implanted in bilateral L4-L5 intertransverse space. At 12 weeks post-surgery, the bone-forming capacities were determined by CT, biomechanical testing, histology, and immunohistochemistry staining analyses. Results. At 12 weeks, the VBPC group significantly increased new bone formation volume compared with the other groups. Biomechanical testing demonstrated higher torque strength in the VBPC group. Notably, the haematoxylin and eosin, Masson’s trichrome, and immunohistochemistry-stained histological results revealed that VBPC promoted neovascularization and new bone formation in the spine fusion areas. Conclusion. The tissue-engineered VBPC showed great capability in promoting angiogenesis and osteogenesis in vivo. It may provide a novel approach to create a superior blood supply and nutritional environment to overcome the deficits of current artificial bone graft substitutes. Cite this article: Bone Joint Res 2023;12(12):722–733

Aims. Lower limb fractures are common in low- and middle-income countries (LMICs) and represent a significant burden to the existing orthopaedic surgical infrastructure. In high income country (HIC) settings, internal fixation is the standard of care due to its superior outcomes. In LMICs, external fixation is often the surgical treatment of choice due to limited supplies, cost considerations, and its perceived lower complication rate. The aim of this systematic review protocol is identifying differences in rates of infection, nonunion, and malunion of extra-articular femoral and tibial shaft fractures in LMICs treated with either internal or external fixation. Methods. This systematic review protocol describes a broad search of multiple databases to identify eligible papers. Studies must be published after 2000, include at least five patients, patients must be aged > 16 years or treated as skeletally mature, and the paper must describe a fracture of interest and at least one of our primary outcomes of interest. We did not place restrictions on language or journal. All abstracts and full texts will be screened and extracted by two independent reviewers. Risk of bias and quality of evidence will be analyzed using standardized appraisal tools. A random-effects meta-analysis followed by a subgroup analysis will be performed, given the anticipated heterogeneity among studies, if sufficient data are available. Conclusion. The lack of easily accessible LMIC outcome data, combined with international clinical guidelines that are often developed by HIC surgeons for use in HIC environments, makes the clinical decision-making process infinitely more difficult for surgeons in LMICs. This protocol will guide research on surgical management, outcomes, and complications of lower limb shaft fractures in LMICs, and can help guide policy development for better surgical intervention delivery and improve global surgical care. Cite this article: Bone Jt Open 2024;5(11):1020–1026

Aims. Given the possible radiation damage and inaccuracy of radiological investigations, particularly in children, ultrasound and superb microvascular imaging (SMI) may offer alternative methods of evaluating new bone formation when limb lengthening is undertaken in paediatric patients. The aim of this study was to assess the use of ultrasound combined with SMI in monitoring new bone formation during limb lengthening in children. Methods. In this retrospective cohort study, ultrasound and radiograph examinations were performed every two weeks in 30 paediatric patients undergoing limb lengthening. Ultrasound was used to monitor new bone formation. The number of vertical vessels and the blood flow resistance index were compared with those from plain radiographs. Results. We categorized the new bone formation into three stages: stage I (early lengthening), in which there was no obvious callus formation on radiographs and ultrasound; stage II (lengthening), in which radiographs showed low-density callus formation with uneven distribution and three sub-stages could be identified on ultrasound: in Ia punctate callus was visible; in IIb there was linear callus formation which was not yet connected and in IIc there was continuous linear callus. In stage III (healing), the bone ends had united, the periosteum was intact, and the callus had disappeared, as confirmed on radiographs, indicating healed bone. A progressive increase in the number of vertical vessels was noted in the early stages, peaking during stages IIb and IIc, followed by a gradual decline (p < 0.001). Delayed healing involved patients with a prolonged stage IIa or those who regressed to stage IIa from stages IIb or IIc during lengthening. Conclusion. We found that the formation of new bone in paediatric patients undergoing limb lengthening could be reliably evaluated using ultrasound when combined with the radiological findings. This combination enabled an improved assessment of the prognosis, and adjustments to the lengthening protocol. While SMI offered additional insights into angiogenesis within the new bone, its role primarily contributed to the understanding of the microvascular environment rather than directly informing adjustments of treatment. Cite this article: Bone Joint J 2024;106-B(7):751–758

Aims. To examine whether natural language processing (NLP) using a clinically based large language model (LLM) could be used to predict patient selection for total hip or total knee arthroplasty (THA/TKA) from routinely available free-text radiology reports. Methods. Data pre-processing and analyses were conducted according to the Artificial intelligence to Revolutionize the patient Care pathway in Hip and knEe aRthroplastY (ARCHERY) project protocol. This included use of de-identified Scottish regional clinical data of patients referred for consideration of THA/TKA, held in a secure data environment designed for artificial intelligence (AI) inference. Only preoperative radiology reports were included. NLP algorithms were based on the freely available GatorTron model, a LLM trained on over 82 billion words of de-identified clinical text. Two inference tasks were performed: assessment after model-fine tuning (50 Epochs and three cycles of k-fold cross validation), and external validation. Results. For THA, there were 5,558 patient radiology reports included, of which 4,137 were used for model training and testing, and 1,421 for external validation. Following training, model performance demonstrated average (mean across three folds) accuracy, F1 score, and area under the receiver operating curve (AUROC) values of 0.850 (95% confidence interval (CI) 0.833 to 0.867), 0.813 (95% CI 0.785 to 0.841), and 0.847 (95% CI 0.822 to 0.872), respectively. For TKA, 7,457 patient radiology reports were included, with 3,478 used for model training and testing, and 3,152 for external validation. Performance metrics included accuracy, F1 score, and AUROC values of 0.757 (95% CI 0.702 to 0.811), 0.543 (95% CI 0.479 to 0.607), and 0.717 (95% CI 0.657 to 0.778) respectively. There was a notable deterioration in performance on external validation in both cohorts. Conclusion. The use of routinely available preoperative radiology reports provides promising potential to help screen suitable candidates for THA, but not for TKA. The external validation results demonstrate the importance of further model testing and training when confronted with new clinical cohorts. Cite this article: Bone Joint J 2024;106-B(7):688–695

Osteoarthritis (OA) is a degenerative disease resulting from progressive joint destruction caused by many factors. Its pathogenesis is complex and has not been elucidated to date. Advanced glycation end products (AGEs) are a series of irreversible and stable macromolecular complexes formed by reducing sugar with protein, lipid, and nucleic acid through a non-enzymatic glycosylation reaction (Maillard reaction). They are an important indicator of the degree of ageing. Currently, it is considered that AGEs accumulation in vivo is a molecular basis of age-induced OA, and AGEs production and accumulation in vivo is one of the important reasons for the induction and acceleration of the pathological changes of OA. In recent years, it has been found that AGEs are involved in a variety of pathological processes of OA, including extracellular matrix degradation, chondrocyte apoptosis, and autophagy. Clearly, AGEs play an important role in regulating the expression of OA-related genes and maintaining the chondrocyte phenotype and the stability of the intra-articular environment. This article reviews the latest research results of AGEs in a variety of pathological processes of OA, to provide a new direction for the study of OA pathogenesis and a new target for prevention and treatment. Cite this article: Bone Joint Res 2022;11(5):292–300

Aims. Unicompartmental and total knee arthroplasty (UKA and TKA) are successful treatments for osteoarthritis, but the solid metal implants disrupt the natural distribution of stress and strain which can lead to bone loss over time. This generates problems if the implant needs to be revised. This study investigates whether titanium lattice UKA and TKA implants can maintain natural load transfer in the proximal tibia. Methods. In a cadaveric model, UKA and TKA procedures were performed on eight fresh-frozen knee specimens, using conventional (solid) and titanium lattice tibial implants. Stress at the bone-implant interfaces were measured and compared to the native knee. Results. Titanium lattice implants were able to restore the mechanical environment of the native tibia for both UKA and TKA designs. Maximum stress at the bone-implant interface ranged from 1.2 MPa to 3.3 MPa compared with 1.3 MPa to 2.7 MPa for the native tibia. The conventional solid UKA and TKA implants reduced the maximum stress in the bone by a factor of 10 and caused > 70% of bone surface area to be underloaded compared to the native tibia. Conclusion. Titanium lattice implants maintained the natural mechanical loading in the proximal tibia after UKA and TKA, but conventional solid implants did not. This is an exciting first step towards implants that maintain bone health, but such implants also have to meet fatigue and micromotion criteria to be clinically viable. Cite this article: Bone Joint Res 2022;11(2):91–101

Aim. The coronavirus disease 2019 (COVID-19) pandemic presents significant challenges to healthcare systems globally. Orthopaedic surgeons are at risk of contracting COVID-19 due to their close contact with patients in both outpatient and theatre environments. The aim of this review was to perform a literature review, including articles of other coronaviruses, to formulate guidelines for orthopaedic healthcare staff. Methods. A search of Medline, EMBASE, the Cochrane Library, World Health Organization (WHO), and Centers for Disease Control and Prevention (CDC) databases was performed encompassing a variety of terms including ‘coronavirus’, ‘covid-19’, ‘orthopaedic’, ‘personal protective environment’ and ‘PPE’. Online database searches identified 354 articles. Articles were included if they studied any of the other coronaviruses or if the basic science could potentially applied to COVID-19 (i.e. use of an inactivated virus with a similar diameter to COVID-19). Two reviewers independently identified and screened articles based on the titles and abstracts. 274 were subsequently excluded, with 80 full-text articles retrieved and assessed for eligibility. Of these, 66 were excluded as they compared personal protection equipment to no personal protection equipment or referred to prevention measures in the context of bacterial infections. Results. There is a paucity of high quality evidence surrounding COVID-19. This review collates evidence from previous coronavirus outbreaks to put forward recommendations for orthopaedic surgeons during the COVID-19 pandemic. The key findings have been summarized and interpreted for application to the orthopaedic operative setting. Conclusion. For COVID-19 positive patients, minimum suggested PPE includes N95 respirator, goggles, face shield, gown, double gloves, and surgical balaclava. Space suits not advised. Be trained in the correct technique of donning and doffing PPE. Use negative pressure theatres if available. Minimize aerosolization and its effects (smoke evacuation and no pulse lavage). Minimize further unnecessary patient-staff contact (dissolvable sutures, clear dressings, split casts)

Aims. As the peak of the COVID-19 pandemic passes, the challenge shifts to safe resumption of routine medical services, including elective orthopaedic surgery. Protocols including pre-operative self-isolation, COVID-19 testing, and surgery at a non-COVID-19 site have been developed to minimize risk of transmission. Despite this, it is likely that many patients will want to delay surgery for fear of contracting COVID-19. The aim of this study is to identify the number of patients who still want to proceed with planned elective orthopaedic surgery in this current environment. Methods. This is a prospective, single surgeon study of 102 patients who were on the waiting list for an elective hip or knee procedure during the COVID-19 pandemic. Baseline characteristics including age, ASA grade, COVID-19 risk, procedure type, surgical priority, and admission type were recorded. The primary outcome was patient consent to continue with planned surgical care after resumption of elective orthopaedic services. Subgroup analysis was also performed to determine if any specific patient factors influenced the decision to proceed with surgery. Results. Overall, 58 patients (56.8%) wanted to continue with planned surgical care at the earliest possibility. Patients classified as ASA I and ASA II were more likely to agree to surgery (60.5% and 60.0%, respectively) compared to ASA III and ASA IV patients (44.4% and 0.0%, respectively) (p = 0.01). In addition, patients undergoing soft tissue knee surgery were more likely to consent to surgery (90.0%) compared to patients undergoing primary hip arthroplasty (68.6%), primary knee arthroplasty (48.7%), revision hip or knee arthroplasty (0.0%), or hip and knee injections (43.8%) (p = 0.03). Conclusion. Restarting elective orthopaedic services during the COVID-19 pandemic remains a significant challenge. Given the uncertain environment, it is unsurprising that only 56% of patients were prepared to continue with their planned surgical care upon resumption of elective services. Cite this article: Bone Joint Open 2020;1-6:267–271

Aims. The use of 3D-printed titanium implant (DT) can effectively guide bone regeneration. DT triggers a continuous host immune reaction, including macrophage type 1 polarization, that resists osseointegration. Interleukin 4 (IL4) is a specific cytokine modulating osteogenic capability that switches macrophage polarization type 1 to type 2, and this switch favours bone regeneration. Methods. IL4 at concentrations of 0, 30, and 100 ng/ml was used at day 3 to create a biomimetic environment for bone marrow mesenchymal stromal cell (BMMSC) osteogenesis and macrophage polarization on the DT. The osteogenic and immune responses of BMMSCs and macrophages were evaluated respectively. Results. DT plus 30 ng/ml of IL4 (DT + 30 IL4) from day 3 to day 7 significantly (p < 0.01) enhanced macrophage type 2 polarization and BMMSC osteogenesis compared with the other groups. Local injection of IL4 enhanced new bone formation surrounding the DT. Conclusion. DT + 30 IL4 may switch macrophage polarization at the appropriate timepoints to promote bone regeneration. Cite this article: Bone Joint Res 2021;10(7):411–424

Objectives. Up to 10% of fractures result in undesirable outcomes, for which female sex is a risk factor. Cellular sex differences have been implicated in these different healing processes. Better understanding of the mechanisms underlying bone healing and sex differences in this process is key to improved clinical outcomes. This study utilized a macrophage–mesenchymal stem cell (MSC) coculture system to determine: 1) the precise timing of proinflammatory (M1) to anti-inflammatory (M2) macrophage transition for optimal bone formation; and 2) how such immunomodulation was affected by male versus female cocultures. Methods. A primary murine macrophage-MSC coculture system was used to demonstrate the optimal transition time from M1 to M2 (polarized from M1 with interleukin (IL)-4) macrophages to maximize matrix mineralization in male and female MSCs. Outcome variables included Alizarin Red staining, alkaline phosphatase (ALP) activity, and osteocalcin protein secretion. Results. We found that 96 hours of M1 phenotype in male cocultures allowed for maximum matrix mineralization versus 72 hours in female cocultures. ALP activity and osteocalcin secretion were also enhanced with the addition of IL-4 later in male versus female groups. The sex of the cells had a statistically significant effect on the optimal IL-4 addition time to maximize osteogenesis. Conclusion. These results suggest that: 1) a 72- to 96-hour proinflammatory environment is critical for optimal matrix mineralization; and 2) there are immunological differences in this coculture environment due to sex. Optimizing immunomodulation during fracture healing may enhance and expedite the bone regeneration response. These findings provide insight into precise immunomodulation for enhanced bone healing that is sex-specific. Cite this article: K. Nathan, L. Y. Lu, T. Lin, J. Pajarinen, E. Jämsen, J-F. Huang, M. Romero-Lopez, M. Maruyama, Y. Kohno, Z. Yao, S. B. Goodman. Precise immunomodulation of the M1 to M2 macrophage transition enhances mesenchymal stem cell osteogenesis and differs by sex. Bone Joint Res 2019;8:481–488. DOI: 10.1302/2046-3758.810.BJR-2018-0231.R2

This article presents a unified clinical theory that links established facts about the physiology of bone and homeostasis, with those involved in the healing of fractures and the development of nonunion. The key to this theory is the concept that the tissue that forms in and around a fracture should be considered a specific functional entity. This ‘bone-healing unit’ produces a physiological response to its biological and mechanical environment, which leads to the normal healing of bone. This tissue responds to mechanical forces and functions according to Wolff’s law, Perren’s strain theory and Frost’s concept of the “mechanostat”. In response to the local mechanical environment, the bone-healing unit normally changes with time, producing different tissues that can tolerate various levels of strain. The normal result is the formation of bone that bridges the fracture – healing by callus. Nonunion occurs when the bone-healing unit fails either due to mechanical or biological problems or a combination of both. In clinical practice, the majority of nonunions are due to mechanical problems with instability, resulting in too much strain at the fracture site. In most nonunions, there is an intact bone-healing unit. We suggest that this maintains its biological potential to heal, but fails to function due to the mechanical conditions. The theory predicts the healing pattern of multifragmentary fractures and the observed morphological characteristics of different nonunions. It suggests that the majority of nonunions will heal if the correct mechanical environment is produced by surgery, without the need for biological adjuncts such as autologous bone graft. Cite this article: Bone Joint J 2016;98-B:884–91

Aims. Spinal deformity surgery carries the risk of neurological injury. Neurophysiological monitoring allows early identification of intraoperative cord injury which enables early intervention resulting in a better prognosis. Although multimodal monitoring is the ideal, resource constraints make surgeon-directed intraoperative transcranial motor evoked potential (TcMEP) monitoring a useful compromise. Our experience using surgeon-directed TcMEP is presented in terms of viability, safety, and efficacy. Methods. We carried out a retrospective review of a single surgeon’s prospectively maintained database of cases in which TcMEP monitoring had been used between 2010 and 2017. The upper limbs were used as the control. A true alert was recorded when there was a 50% or more loss of amplitude from the lower limbs with maintained upper limb signals. Patients with true alerts were identified and their case history analyzed. Results. Of the 299 cases reviewed, 279 (93.3%) had acceptable traces throughout and awoke with normal clinical neurological function. No patient with normal traces had a postoperative clinical neurological deficit. True alerts occurred in 20 cases (6.7%). The diagnoses of the alert group included nine cases of adolescent idiopathic scoliosis (AIS) (45%) and six of congenital scoliosis (30%). The incidence of deterioration based on diagnosis was 9/153 (6%) for AIS, 6/30 (20%) for congenital scoliosis, and 2/16 (12.5%) for spinal tuberculosis. Deterioration was much more common in congenital scoliosis than in AIS (p = 0.020). Overall, 65% of alerts occurred during rod instrumentation: 15% occurred during decompression of the internal apex in vertebral column resection surgery. Four alert cases (20%) awoke with clinically detectable neurological compromise. Conclusion. Surgeon-directed TcMEP monitoring has a 100% negative predictive value and allows early identification of physiological cord distress, thereby enabling immediate intervention. In resource constrained environments, surgeon-directed TcMEP is a viable and effective method of intraoperative spinal cord monitoring. Level of evidence: III. Cite this article: Bone Joint J 2021;103-B(3):547–552

Bone is a dynamic tissue with a quarter of the trabecular and a fifth of the cortical bone being replaced continuously each year in a complex process that continues throughout an individual’s lifetime. Bone has an important role in homeostasis of minerals with non-stoichiometric hydroxyapatite bone mineral forming the inorganic phase of bone. Due to its crystal structure and chemistry, hydroxyapatite (HA) and related apatites have a remarkable ability to bind molecules. This review article describes the accretion of trace elements in bone mineral giving a historical perspective. Implanted HA particles of synthetic origin have proved to be an efficient recruiting moiety for systemically circulating drugs which can locally biomodulate the material and lead to a therapeutic effect. Bone mineral and apatite however also act as a waste dump for trace elements and drugs, which significantly affects the environment and human health. Cite this article: Bone Joint Res 2020;9(10):709–718

Bone is one of the most highly adaptive tissues in the body, possessing the capability to alter its morphology and function in response to stimuli in its surrounding environment. The ability of bone to sense and convert external mechanical stimuli into a biochemical response, which ultimately alters the phenotype and function of the cell, is described as mechanotransduction. This review aims to describe the fundamental physiology and biomechanisms that occur to induce osteogenic adaptation of a cell following application of a physical stimulus. Considerable developments have been made in recent years in our understanding of how cells orchestrate this complex interplay of processes, and have become the focus of research in osteogenesis. We will discuss current areas of preclinical and clinical research exploring the harnessing of mechanotransductive properties of cells and applying them therapeutically, both in the context of fracture healing and de novo bone formation in situations such as nonunion. Cite this article: Bone Joint Res 2019;9(1):1–14

Aims. Current treatments of prosthetic joint infection (PJI) are minimally effective against Staphylococcus aureus biofilm. A murine PJI model of debridement, antibiotics, and implant retention (DAIR) was used to test the hypothesis that PlySs2, a bacteriophage-derived lysin, can target S. aureus biofilm and address the unique challenges presented in this periprosthetic environment. Methods. The ability of PlySs2 and vancomycin to kill biofilm and colony-forming units (CFUs) on orthopaedic implants were compared using in vitro models. An in vivo murine PJI model of DAIR was used to assess the efficacy of a combination of PlySs2 and vancomycin on periprosthetic bacterial load. Results. PlySs2 treatment reduced 99% more CFUs and 75% more biofilm compared with vancomycin in vitro. A combination of PlySs2 and vancomycin in vivo reduced the number of CFUs on the surface of implants by 92% and in the periprosthetic tissue by 88%. Conclusion. PlySs2 lysin was able to reduce biofilm, target planktonic bacteria, and work synergistically with vancomycin in our in vitro models. A combination of PlySs2 and vancomycin also reduced bacterial load in periprosthetic tissue and on the surface of implants in a murine model of DAIR treatment for established PJI. Cite this article: Bone Joint J 2020;102-B(7 Supple B):3–10