bluuebunny/crossref_metadata_2025 huggingface dataset:
HIP ARTHROSCOPY FOR THE PRIMARY MANAGEMENT OF FEMOROACETABULAR IMPINGEMENT WITH CONCOMITANT CHONDRAL LESIONS ACCORDING TO THE OUTERBRIDGE CLASSIFICATION: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Lu V. , Andronic O. , Zhang J. , Khanduja V.
Published: July 2023

Arthroscopic management of femoroacetabular impingement (FAI) has become the mainstay of treatment. However, chondral lesions are frequently encountered and have become a determinant of less favourable outcomes following arthroscopic intervention.

The aim of this systematic review and meta-analysis was to assess the outcomes of hip arthroscopy (HA) in patients with FAI and concomitant chondral lesions classified as per Outerbridge.

A systematic search was performed using the PRISMA guidelines on four databases including MEDLINE, EMBASE, Cochrane Library and Web of Science. Studies which included HA as the primary intervention for management of FAI and classified chondral lesions according to the Outerbridge classification were included. Patients treated with open procedures, for osteonecrosis, Legg-Calve-Perthes disease, and previous ipsilateral hip fractures were excluded. From a total of 863 articles, twenty-four were included for final analysis. Demographic data, PROMs, and radiological outcomes and rates of conversion to total hip arthroplasty (THA) were collected. Risk of bias was assessed using ROBINS-I.

Improved post-operative PROMs included mHHS (mean difference:-2.42; 95%CI:-2.99 to −1.85; p<0.001), NAHS (mean difference:-1.73; 95%CI: −2.23 to −1.23; p<0.001), VAS (mean difference: 2.03; 95%CI: 0.93-3.13; p<0.001). Pooled rate of revision surgery was 10% (95%CI: 7%-14%). Most of this included conversion to THA, with a 7% pooled rate (95%CI: 4%-11%).

Patients had worse PROMs if they underwent HA with labral debridement (p=0.015), had Outerbridge 3 and 4 lesions (p=0.012), concomitant lesions of the femoral head and acetabulum lesions (p=0.029). Reconstructive cartilage techniques were superior to microfracture (p=0.042). Even in concomitant lesions of the femoral head and acetabulum, employing either microfracture or cartilage repair/reconstruction provided a benefit in PROMs (p=0.027).

Acceptable post-operative outcomes following HA with labral repair/reconstruction and cartilage repair in patients with FAI and concomitant moderate-to-severe chondral lesions, can be achieved. Patients suffering from Outerbridge 3 and 4 lesions, concomitant acetabular rim and femoral head chondral lesions that underwent HA with labral debridement, had worse PROMs. Reconstructive cartilage techniques were superior to microfracture. Even in concomitant acetabular and femoral head chondral lesions, employing either microfracture or cartilage repair/reconstruction was deemed to provide a benefit in PROMs.
LIVER DISEASE IS A RISK FACTOR FOR ACUTE SEPTIC ARTHRITIS: RESULTS FROM A MAJOR TRAUMA CENTRE
Authors: Lu V. , Zhou A. , Hussain H. , Thahir A. , Krkovic M.
Published: July 2023

A hot swollen joint is a commonly encountered condition in clinical practice. With a broad range of differentials, septic arthritis (SA) is perhaps one of the most concerning. Treated by culture-specific antibiotics and arthroscopic lavage, some patients require multiple washouts. We aimed to determine:

(1) What are the risk factors for development of SA?

(2) What are the risk factors for repeat washout in SA patients?

(3) What are the important clinical differences between a periprosthetic joint infection (PJI) and SA cohort?

All patients presenting to the emergency department, orthopaedic, and rheumatology clinics between January 2020 to January 2021 with a hot, swollen joint were retrospectively evaluated. Patients with previous trauma on the ipsilateral joint, with data missing from their medical records in any of the variables required for analysis, <24 months follow-up were excluded.

Variables of interest in the three-month period preceding the diagnosis of SA were compared between SA and non-SA patients. Factors with a p-value of p<0.100 in univariate analysis were included in a stepwise multivariate logistic regression model. Similar analyses were performed to compare SA patients with multiple washouts with those needing one washout. Demographical and clinical data for PJI patients were collected to delineate important differences with SA cohort.

211 patients were included (SA:28;PJI:24;pseudogout:32;gout:26;others:101). Multivariate analysis showed rheumatoid arthritis (RA), skin infection, and liver disease were risk factors for SA. Amongst patients with septic arthritis, multivariate analysis showed that WBC levels above normal limits (3.6-10.5×109 cells/L) and RA were risk factors for multiple washouts.

Between the SA and PJI cohorts, BMI (p=0.002) was significantly lower in the former, whilst WBC level (p=0.023) and CRP (p<0.0001) was significantly higher in the former.

Early diagnosis of septic arthritis requires understanding the risk factors, namely RA, skin infection, and liver disease. Considering PJI and septic arthritis as the same entity can lead to wrong clinical judgement, and clinicians should be aware of important differences. We believe that the models in this study are of prognostic value to clinicians who are presented with the common presenting compliant of a hot swollen joint.
INTRAMUSCULAR INTERPOSITION OF NERVE ENDINGS TO MINIMIZE NEUROPATHIC AND RESIDUAL PAIN IN LOWER LIMB AMPUTEES
Authors: Lu V. , Zhou A. , Krkovic M.
Published: July 2023

A major cause of morbidity in lower limb amputees is phantom limb pain (PLP) and residual limb pain (RLP). This study aimed to determine if surgical interposition of nerve endings into adjacent muscle bellies at the time of major lower limb amputation can decrease the incidence and severity of PLP and RLP.

Data was retrospectively collected from January 2015 to January 2021, including eight patients that underwent nerve interposition (NI) and 36 that received standard treatment. Primary outcomes included the 11-point Numerical Rating Scale (NRS) for pain severity, and Patient-Reported Outcomes Measurement Information System (PROMIS) pain intensity, behaviour, and interference. Secondary outcome included Neuro-QoL Lower Extremity Function assessing mobility. Cumulative scores were transformed to standardised t scores.

Across all primary and secondary outcomes, NI patients had lower PLP and RLP. Mean ‘worst pain’ score was 3.5 out of 10 for PLP in the NI cohort, compared to 4.89 in the control cohort (p=0.298), and 2.6 out of 10 for RLP in the NI cohort, compared to 4.44 in the control cohort (p=0.035). Mean ‘best pain’ and ‘current pain’ scores were also superior in the NI cohort for PLP (p=0.003, p=0.022), and RLP (p=0.018, p=0.134).

Mean PROMIS t scores were lower for the NI cohort for RLP (40.1 vs 49.4 for pain intensity; p=0.014, 44.4 vs 48.2 for pain interference; p=0.085, 42.5 vs 49.9 for pain behaviour; p=0.025). Mean PROMIS t scores were also lower for the NI cohort for PLP (42.5 vs 52.7 for pain intensity; p=0.018); 45.0 vs 51.5 for pain interference; p=0.015, 46.3 vs 51.1 for pain behaviour; p=0.569). Mean Neuro-QoL t score was lower in NI cohort (45.4 vs 41.9;p=0.03).

Surgical interposition of nerve endings during lower limb amputation is a simple yet effective way of minimising PLP and RLP, improving patients’ subsequent quality of life. Additional comparisons with targeted muscle reinnervation should be performed to determine the optimal treatment option.
INVESTIGATING THE OPTIMAL VIRTUAL REALITY TRAINING STRATEGY: A RANDOMIZED CONTROLLED TRIAL COMPARING SPACED VERSUS MASSED TRAINING IN THE DIRECT ANTERIOR APPROACH FOR TOTAL HIP ARTHROPLASTY
Authors: Edwards T. , Khan S. , Patel A. , Gupta S. , Soussi D. , Liddle A. , Cobb J. , Logishetty K.
Published: July 2023

Evidence supporting the use of virtual reality (VR) training in orthopaedic procedures is rapidly growing. However, the impact of the timing of delivery of this training is yet to be tested. We aimed to investigate whether spaced VR training is more effective than massed VR training.

24 medical students with no hip arthroplasty experience were randomised to learning the direct anterior approach total hip arthroplasty using the same VR simulation, training either once-weekly or once-daily for four sessions. Participants underwent a baseline physical world assessment on a saw bone pelvis. The VR program recorded procedural errors, time, assistive prompts required and hand path length across four sessions. The VR and physical world assessments were repeated at one-week, one-month, and 3 months after the last training session.

Baseline characteristics between the groups were comparable (p > 0.05). The daily group demonstrated faster skills acquisition, reducing the median ± IQR number of procedural errors from 68 ± 67.05 (session one) to 7 ± 9.75 (session four), compared to the weekly group's improvement from 63 ± 27 (session one) to 13 ± 15.75 (session four), p < 0.001. The weekly group error count plateaued remaining at 14 ± 6.75 at one-week, 16.50 ± 16.25 at one-month and 26.45 ± 22 at 3-months, p < 0.05. However, the daily group showed poorer retention with error counts rising to 16 ± 12.25 at one-week, 17.50 ± 23 at one-month and 41.45 ± 26 at 3-months, p<0.01. A similar effect was noted for the number of assistive prompts required, procedural time and hand path length. In the real-world assessment, both groups significantly improved their acetabular component positioning accuracy, and these improvements were equally maintained (p<0.01).

Daily VR training facilitates faster skills acquisition; however weekly practice has superior skills retention.
HUCMSCS-DERIVED EXOSOMES SUPPRESS OSTEOARTHRITIS IN RABBITS THROUGH INHIBITING CCL2
Authors: Ding Y. , Wu C. , Li S. , Sun Y. , Lin S. , Wen Z. , Ouyang Z.
Published: July 2023

Osteoarthritis (OA), the most prevalent chronic joint disease, represents a relevant social and economic burden worldwide. Human umbilical cord mesenchymal stem cells (HUCMSCs) have been used for injection into the joint cavity to treat OA. The aim of this article is to clarify whether Huc-MSCs derived exosomes could inhibit the progression of OA and the mechanism in this process.

A rabbit OA model was established by the transection of the anterior cruciate ligament. The effects of HUCMSCs or exosomes derived from HUCMSCs on repairing articular cartilage of knee osteoarthritis was examined by micro-CT. Immunohistochemical experiments were used to confirm the expression of relevant inflammatory molecules in OA. In vitro experiments, Transwell assay was used to assess the migration of macrophages induced by TNF-a.

Results showed that a large number of macrophages migrated in arthcular cavity in OA model in vivo, while local injection of HUCMSCs and exosomes did repair the articular cartilage. Immunohistochemical results suggested that the expression of CCL2 and CD68 in the OA rabbit model increased significantly, but was significantly reduced by HUCMSCs or exosomes. Transwell assay showed that both HUCMSCs and exosomes can effectively inhibit the migration of macrophage.

In conclusion, the exosomes derived by HUCMSCs might might rescue cartilage defects in rabbit through its anti-inflammatory effects through inhibiting CCL2.
DMP1 POSITIVE ASTROCYTES MAINTAIN BLOOD-BRAIN BARRIER VIA TRANSFERRING MITOCHONDRIA TO VASCULAR ENDOTHELIAL CELLS
Authors: Liu D. , Gao J. , Zheng M. , Liao P. , Li H. , Zhang C.
Published: July 2023

Though dentin matrix protein 1 (Dmp1) is known to play critical role in mediating bone mineralization, it has also been validated to be expressed in brain and helps maintain blood brain barrier (BBB). Our study aims to clarify the expression pattern of Dmp1 in mouse brain and explore whether intercellular mitochondrial transfer occurs between Dmp1 positive astrocytes (DPAs) and endothelial cells, and thus acting as a mechanism in maintaining BBB during aging.

Single cell RNA sequencing (scRNAseq) of 1 month, 6 month, and 20 month old mice brain (n=1, respectively) was employed to identify Dmp1 positive cell types. Dmp1Cre-mGmT and Dmp1Cre-COX8a fluorescent mice were generated to visualize DPAs and investigate their mitochondrial activities. A 3D noncontact coculture system and mitochondrial transplantation were applied to study the role of mitochondrial transfer between astrocytes and bEnd.3 endothelial cells. Dmp1Cre-Mfn2f/f mice were generated by depleting the ER-mitochondria tethering protein Mfn2 in DPAs.

Dmp1 was mainly expressed in astrocytes at different ages. GO analysis revealed that cell projection and adhesion of DPAs were upregulated. Confocal imaging on Dmp1Cre-mGmT mice indicated that DPAs are a cluster of astrocytes that closely adhere to blood vessels (n=3). Bioinformatics analysis revealed that mitochondrial activity of DPAs were compromised during aging. Enriched scRNAseq of fluorescent cells from Dmp1Cre-COX8a mice (n=2) and immunofluorescent imaging (n=3) validated the acquisition of extrinsic mitochondria in endothelial cells. 3D coculture of astrocytes and bEnd.3 and direct mitochondrial transplantation revealed the rescue effect of mitochondrial transfer on damaged bEnd.3. BBB was impaired after depleting Mfn2 in DPAs, expressing a similar phenotype with aging brain.

Astrocytes that express Dmp1 play a significant role in maintaining BBB via transferring mitochondria to vascular endothelial cells. Compromised mitochondrial transfer between DPAs and endothelial cells might be the potential mechanism of impaired BBB during aging.
A RELIABLE PREDICTOR OF SECONDARY LATERAL WALL FRACTURE FOLLOWING TROCHANTERIC FRACTURES: AN UPDATE
Authors: van Knegsel K.P. , Hsu C-E , Huang K-C , Benca E. , Ganse B. , Pastor T. , Gueorguiev B. , Varga P. , Knobe M.
Published: July 2023

The lateral wall thickness (LWT) in trochanteric femoral fractures is a known predictive factor for postoperative fracture stability. Currently, the AO/OTA classification uses a patient non-specific measure to assess the absolute LWT (aLWT) and distinguish stable A1.3 from unstable A2.1 fractures based on a threshold of 20.5 mm. This approach potentially results in interpatient deviations due to different bone morphologies and consequently variations in fracture stability. Therefore, the aim of this study was to explore whether a patient-specific measure for assessment of the relative LWT (rLWT) results in a more precise threshold for prediction of unstable fractures.

Part 1 of the study evaluated 146 pelvic radiographs to assess left-right symmetry with regard to caput-collum-angle (CCD) and total trochanteric thickness (TTT), and used the results to establish the rLWT measurement technique. Part 2 reevaluated 202 patients from a previous study cohort to analyze their rLWT versus aLWT for optimization purposes.

Findings in Part 1 demonstrated a bilateral symmetry of the femur regarding both CCD and TTT (p ≥ 0.827) allowing to mirror bone's morphology and geometry from the contralateral intact to the fractured femur. Outcomes in Part 2 resulted in an increased accuracy for the new determined rLWT threshold (50.5%) versus the standard 20.5 mm aLWT threshold, with sensitivity of 83.7% versus 82.7% and specificity 81.3% versus 77.8%, respectively.

The novel patient-specific rLWT measure can be based on the contralateral femur anatomy and is a more accurate predictor of a secondary lateral wall fracture in comparison to the conventional aLWT. This study established the threshold of 50.5% rLWT as a reference value for prediction of fracture stability and selection of an appropriate implant for fixation of trochanteric femoral fractures.
IMPROVEMENT IN OSTEOCONDUCTIVITY OF MINISCREW IMPLANTS BY THE BIOMIMETIC CALCIUM PHOSPHATE COATINGS IN THE PRESENCE AND ABSENCE OF BOVINE SERUM ALBUMIN
Authors: Li M. , Wu G. , Liu Y.
Published: July 2023

Miniscrew implants (MSIs) are widely used to provide absolute anchorage for the orthodontic treatment. However, the application of MSIs is limited by the relatively high failure rate (22.86%). In this study, we wished to investigate the effects of amorphous and crystalline biomimetic calcium phosphate coating on the surfaces of MSIs with or without the incorporated BSA for the osteointegration process with an aim to facilitate the early loading of MSIs.

Amorphous and crystalline coatings were prepared on titanium mini-pin implants. Characterizations of coatings were examined by Scanning electron microscopy (SEM), Confocal laser-scanning dual-channel-fluorescence microscopy (CLSM) and Fourier-transform infrared spectroscopy (FTIR). The loading and release kinetics of bovine serum albumin (BSA) were evaluated by Enzyme linked immunosorbent assay (ELISA). Activity of alkaline phosphate (ALP) was measured by using the primary osteoblasts. In vivo, a model of metaphyseal tibial implantation in rats was used (n=6 rats per group). We had 6 different groups: no coating no BSA, no coating but with surface adsorption of BSA and incorporation of BSA in the biomimetic coating in the amorphous and crystalline coatings. Time points were 3 days, 1, 2 and 4 weeks. Histological and histomorphometric analysis were performed and the bone to implant contact (BIC) of each group was compared.

In vitro, the incorporation of BSA changed the crystalline coating from sharp plates into curly plates, and the crystalline coating showed slow-release profile. The incorporation of BSA in crystalline coating significantly decreased the activity of ALP in vitro. In vivo study, the earliest significant increase of BIC appeared in crystalline coating group at one week.

The crystalline coating can serve as a carrier and slow release system for the bioactive agent and accelerate osteoconductivity at early stage in vivo. The presence of BSA is not favorable for the early establishment of osteointegration.
THE IMPORTANCE OF PRESS-FIT AND THREE-POINT FIXATION IN TREATING LARGE ACETABULAR DEFECTS WITH POROUS TANTALUM COMPONENTS
Authors: Callary S. , Abrahams J. , Zeng Y. , Clothier R. , Costi K. , Campbell D. , Howie D. , Solomon L.B.
Published: July 2023

First-time revision acetabular components have a 36% re-revision rate at 10 years in Australia, with subsequent revisions known to have even worse results. Acetabular component migration >1mm at two years following revision THA is a surrogate for long term loosening. This study aimed to measure the migration of porous tantalum components used at revision surgery and investigate the effect of achieving press-fit and/or three-point fixation within acetabular bone.

Between May 2011 and March 2018, 55 patients (56 hips; 30 female, 25 male) underwent acetabular revision THR with a porous tantalum component, with a post-operative CT scan to assess implant to host bone contact achieved and Radiostereometric Analysis (RSA) examinations on day 2, 3 months, 1 and 2 years. A porous tantalum component was used because the defects treated (Paprosky IIa:IIb:IIc:IIIa:IIIb; 2:6:8:22:18; 13 with pelvic discontinuity) were either deemed too large or in a position preventing screw fixation of an implant with low coefficient of friction. Press-fit and three-point fixation of the implant was assessed intra-operatively and on postoperative imaging.

Three-point acetabular fixation was achieved in 51 hips (92%), 34 (62%) of which were press-fit. The mean implant to host bone contact achieved was 36% (range 9-71%). The majority (52/56, 93%) of components demonstrated acceptable early stability. Four components migrated >1mm proximally at two years (1.1, 3.2, 3.6 and 16.4mm). Three of these were in hips with Paprosky IIIB defects, including 2 with pelvic discontinuity. Neither press-fit nor three-point fixation was achieved for these three components and the cup to host bone contact achieved was low (30, 32 and 59%).

The majority of porous tantalum components had acceptable stability at two years following revision surgery despite treating large acetabular defects and poor bone quality. Components without press-fit or three-point fixation were associated with unacceptable amounts of early migration.
COVID-19 INFECTION RATE IN THE PERIOPERATIVE PERIOD FOR PATIENTS UNDERGOING ELECTIVE ORTHOPAEDIC SURGERY
Authors: Sankar S. , Kadakia A. , Szanto E.
Published: July 2023

COVID-19 was declared a pandemic by the World Health Organization (WHO) on 11 March 2020. The initial response to the pandemic included the cessation of routine services including elective orthopaedic surgery. There was apprehension among both surgeons and patients about restarting elective surgical services. The high mortality rate in perioperative patients who contract COVID-19 was of particular concern. The aim of this study was to identify the perioperative viral transmission rate in orthopaedic patients at our institution following the restart of elective surgery between August 2020 and November 2020 after the first wave of Covid in the UK.

All patients who had their elective Orthopaedic surgeries at our institution from 1st August 2020 to 30th November 2020 were checked whether they were Covid positive or experienced COVID symptoms within 2 weeks after the operation. All patients were advised a 14-day period of comprehensive social distancing, 3 days of self-isolation and had a negative COVID-19 test within 72 hours of surgery and underwent surgery at a COVID free site. The patients were contacted and the hospital database was searched to identify those patients who were Covid positive or had Covid symptoms after the surgery. Baseline patient characteristics were recorded including age, gender, procedure, the subspeciality and admission type. Patients who underwent emergency procedures and trauma operations were excluded.

Out of the 499 patients, 315 were contacted over telephone and hospital database was searched for the rest of the patients. We found that none of the patients were positive for COVID or had symptoms of COVID within two weeks of surgery. 5 patients were COVID positive with symptoms few months after the procedure and all of them recovered. There were 144 inpatient admissions and 353 day cases.

The development of a COVID-free pathway for elective orthopaedic patients results in very low viral transmission rates. Findings of our study confirms that COVID-free elective pathway is an efficient process, and this could be implemented in future elective Orthopaedic surgeries during COVID times. Elective surgery can be safely resumed using dedicated pathways and procedures -Surgeons, hospital staff and patients should remain vigilant.
AN EXPERIMENTAL INVESTIGATION OF THE MICROARCHITECTURE AND FRACTURE MECHANICS OF FEMURS OF ZUCKER DIABETIC FATTY (ZDF) RATS USING A SIDEWAYS FALL TEST
Authors: Monahan G.E. , Schiavi-Tritz J. , Vaughan T.J.
Published: July 2023

This study aims to assess the fracture mechanics of type-2 diabetic (T2D) femoral bone using innovative site-specific tests, whilst also examining the cortical and trabecular bone microarchitecture from various regions using micro-computed tomography (CT) of the femur as the disease progresses.

Male [Zucker Diabetic Fatty (ZDF: fa/fa) (T2D) and Zucker Lean (ZL: fa/+) (Control)] rats were euthanized at 12-weeks of age, thereafter, right and left femora were dissected (Right femora: n = 6, per age, per condition; Left femora: n=8-9, per age, per condition). Right femurs were notched in the posterior of the midshaft. Micro-CT was used to scan the proximal femur, notched and unnotched femoral midshaft (cortical) of the right femur and the distal metaphysis (trabecular) of the left femur to investigate microarchitecture and composition. Right femurs were fracture toughness tested to measure the stress intensity factor (Kic) followed by a sideways fall test using a custom-made rig to investigate femoral neck mechanical properties.

There was no difference in trabecular and cortical tissue material density (TMD) between T2D and control rats. Cortical thickness was unchanged, but trabeculae were thinner (p<0.01) in T2D rats versus controls. However, T2D rats had a greater number of trabeculae (p<0.05) although trabecular spacing was not different to controls. T2D rats had a higher connectivity distribution (p<0.05) and degree of anisotropy (p<0.05) in comparison to controls. There was no difference in the mechanical properties between strains.

At 12-weeks of age, rats are experiencing early-stage T2Ds and the disease impact is currently not very clear. Structural and material properties are unchanged between strains, but the trabecular morphology shows that T2D rats have more trabecular struts present in order to account for the thinner trabeculae.
EFFICACY OF SALINE WASH PLUS VANCOMYCIN/TOBRAMYCIN-DOPED PVA COMPOSITE (PVA-VAN/TOB-P) IN A MOUSE POUCH INFECTION MODEL IMPLANTED WITH 3D-PRINTED POROUS TITANIUM CYLINDERS
Authors: Markel D. , Dietz P. , Wu B. , Bou-Akl T. , Ren W.
Published: July 2023

The efficacy of saline irrigation for the treatment of periprosthetic infection (PJI) is limited in the presence of infected implants. This study evaluated the efficacy of vancomycin/tobramycin-doped polyvinyl alcohol (PVA)/ceramic composites (PVA-VAN/TOB-P) after saline irrigation in a mouse pouch infection model.

3D printed porous titanium (Ti) cylinders (400, 700 and 100 µm in pore size) were implanted into mice pouches, then inoculated with S. aureus at the amounts of 1X103 CFU and 1X106 CFU per pouch, respectively. Mice were randomized into 4 groups (n=6 for each group): (1) no bacteria; (2) bacteria without saline wash; 3) saline wash only, and (4) saline wash+PVA-VAN/TOB-P. After seven days, pouches were washed out alone or with additional injection of 0.2 ml of PVA-VAN/TOB-P. Mice were sacrificed 14 days after pouch wash. Bacteria cultures of collected Ti cylinders and washout fluid and histology of pouch tissues were performed.

The low-grade infection (1X103 CFU) was more significant in 400 µm Ti cylinders than that in Ti cylinders with larger pore sizes (700 and 1000 µm (p<0.05). A similar pattern of high-grade infection (1X106 CFU) was observed (p<0.05). For the end wash, the bacteria burden (0.49±0.02) in saline wash group was completely eradicated by the addition of PVA-VAN/TOB-P (0.005±0.001, p<0.05).

We noticed that 400 µm Ti cylinders have the highest risk of implant infection. Our data supported that the effect of saline irrigation was very limited in the presence of contaminated porous Ti cylinders. PVA-VAN/TOB-P was biodegradable, biocompatible, and was effective in eradicating bacteria retention after saline irrigation in a mouse model of low grade and high-grade infection. We believe that PVA-VAN/TOB-P represents an alternative to reduce the risk of PJI by providing a sustained local delivery of antibiotics.
TENSILE PROPERTIES OF TENDON AFTER REPAIR USING TITANIUM IMPLANTS WITH DIFFERENT POROSITIES IN A RAT MODEL
Authors: Fry M. , Ren W. , Bou-Akl T. , Wu B. , Cizmic Z. , Markel D.
Published: July 2023

Extensor mechanism and abductor reconstructions in total joint arthroplasty are problematic. Growing tendon into a metallic implant would have great reconstructive advantages. With the introduction of porous metal implants, it was hoped that tendons could be directly attached to implants. However, the effects of the porous metal structure on tissue growth and pore penetration is unknown. In this rat model, we investigated the effect of pore size on tendon repair fixation using printed titanium implants with differing pore sizes.

There were four groups of six Sprague Dawley rats (n = 28) plus control (n=4). Implants had pore sizes of 400µm (n=8), 700µm (n=8), and 1000µm (n=8). An Achilles tendon defect was created, and the implant positioned and sutured between the cut ends. Harvest occurred at 12-weeks. Half the specimens underwent tensile load to failure testing, the other half fixed and processed for hard tissue analysis.

Average load to failure was 72.6N for controls (SD 10.04), 29.95N for 400µm (SD 17.95), 55.08N for 700µm (SD 13.47), and 63.08N for 1000µm (SD 1.87). The load to failure was generally better in the larger pore sizes. Histological evaluation showed that there was fibrous tendon tissue within and around the implant material, with collagen fibers organized in bundles. This increases as the pore diameter increases.

Printing titanium implants allows for precise determination of pore size and structure. Our results showed that tendon repair utilizing implants with 700µm and 1000µm pores exhibited similar load to failure as controls. Using a defined pore structure at the attachment points of tendons to implants may allow predictable tendon to implant reconstruction at the time of revision arthroplasty.
MUSSEL ADHESIVE PROTEIN-BASED ADHESIVE TO RETAIN STEM CELLS FOR CARTILAGE REGENERATION
Authors: Ko J-Y. , Lee E. , Cha H.J. , Im G-I.
Published: July 2023

In this study, we developed biocompatible adhesive which enables implanted chondrogenic-enhanced hASCs being strongly fixed to the lesion site of defected cartilage.

The bioengineered mussel adhesive protein (MAP) was produced and purified using a bacterial expression system as previously reported. The cell encapsulated coacervate was formulated with two polyelectrolyte, the MAP and 723kDa hyaluronic acid (HA). MAP formed liquid microdroplets with HA and subsequently gelated into microparticles, which is highly viscous and strongly adhesive.

The MAP with chondro-induced hASCs were implanted on the osteochondral defect created in the patellar groove/condyle of OA-induced rabbits. Rabbits were allocated to three different groups as follows: Group1 – Fibrin only; Group2 – Fibrin with hASCs (1.5×106 chondro-induced hASCs); Group3; MAP with hASCs.

The implanted cells were labeled with a fluorescent dye for in vivo visualization. After 35 days, fluorescent signals were more potently detected for MAP with hASCs group than Fibrin with hASCs group in osteochondral defect model. Moreover, histological assessment showed that MAP with hASCs group had the best healing and covered with hyaline cartilage-like tissue. The staining image shows that MAP with hASCs group were filled with perfectly differentiated chondrocytes. Although Fibrin with hASCs group had better healing than fibrin only group, it was filled with fibrous cartilage which owes its flexibility and toughness. As MAP with hASCs group has higher possibility of differentiating to complete cartilage, Fibrin only group and Fibrin with hASCs group have failed to treat OA by rehabilitating cartilage. In order to clarify the evidence of remaining human cell proving efficacy of newly developed bioadhesive, human nuclear staining was proceeded with sectioned rabbit cartilage tissue. The results explicitly showed MAP with hASCs group have retained more human cells than Fibrin only and Fibrin with hASCs groups.

We investigated the waterproof bioadhesive supporting transplanted cells to attach to defect lengthily in harsh environment, which prevents cells from leaked to other region of cartilage. Collectively, the newly developed bio-adhesive, MAP, could be successfully applied in OA treatment as a waterproof bioadhesive with the capability of the strong adhesion to target defect sites.
EFFECTS OF WOUND IRRIGATION SOLUTIONS ON HOST TISSUE: MURINE AIR POUCH INFECTION MODEL
Authors: Markel D. , Chatterji R. , Bou-Akl T. , Wu B. , Dietz P. , Ren W.
Published: July 2023

Irrigation with antiseptic agents, antibiotics, and surfactants are used for treatment and prevention of infections. Despite desirable microbicidal actions, studies have demonstrated cytotoxic effects on host tissue that may impair healing. This study investigated the extent of tissue damage caused by commonly used irrigation solutions in the presence or absence of infection.

Air pouches created in 60 balb/c mice were divided into two groups (n=30): infected with Staphylococcus aureus and control. One week later the infected group was subdivided into 5 subgroups (n=6) based on irrigation solutions and by day 0 (immediately) and day7 after irrigation (n=3). Solutions included Saline, Bacitracin, Clorpactin, Irrisept and Bactisure. In infected group wash fluid was collected for quantitative analysis of bacterial growth. At the specified times mice were sacrificed, pouch tissue sent for histology, and sections analyzed for inflammation, necrosis, and edema.

Inflammation decreased in infected vs sterile pouches for all solutions except Bacitracin day 0 and for all solutions day 7 with significance in all except Bacitracin (p<0.05). On day 0, necrosis increased in infected vs sterile pouches in Bacitracin (p=0.006), Irrisept (p=0.18), or Bactisure (p=0.07); however, on day 7, necrosis significantly decreased in infected pouches for all solutions (p<0.05) except for Clorpactin (p=0.18). Edema decreased in infected vs sterile pouches on day 0 for all solutions with significance in saline, Irrisept, and Bacitracin (p<0.05). On day 7, infected pouches had decreased edema in saline, Bacitracin, and Bactisure (p<0.05) and increased in Irrisept (p<0.05) and Clorpactin (p=0.069) compared to sterile pouches. Bacterial culture of washouts demonstrated that Clorpactin, Irrisept and Bactisure controlled the infection, whereas saline and Bacitracin showed bacterial multiplication 3.9 × 10^7 CFU/ml and 6.7 × 10^7 CFU/ml respectively. Bacitracin wash showed significantly more bacteria growth compared to Clorpactin (p=0.024), Irrisept (p=0.025) and Bactisure (p=0.025).

Tissue damage varied with irrigation solutions and the presence or absence of infection. Presence of bacteria appeared to lead to less tissue inflammation and edema. Tissue necrosis varied over time with different solutions. Surgeons must weigh risks and benefits when selecting solutions and determining when to irrigate.
EXPERIMENTALLY VALIDATED COMPUTER SIMULATIONS OF LOCKING PLATE FIXATIONS FOR SURGICAL EDUCATION
Authors: Mischler D. , Knecht M. , Varga P.
Published: July 2023

Surgical education of fracture fixation biomechanics relies mainly on simplified illustrations to distill the essence of the underlying principles. These mostly consist of textbook drawings or hands-on exercises during courses, both with unique advantages such as broad availability and haptics, respectively. Computer simulations are suited to bridge these two approaches; however, the validity of such simulations must be guaranteed to teach the correct aspects. Therefore, the aim of this study was to validate finite element (FE) simulations of bone-plate constructs to be used in surgical education in terms of fracture gap movement and implant surface strain.

The validation procedure was conducted in a systematic and hierarchical manner with increasing complexity. First, the material properties of the isolated implant components were determined via four-point bending of the plate and three-point bending of the screw. Second, stiffness of the screw-plate interface was evaluated by means of cantilever bending to determine the properties of the locking mechanism. Third, implant surface strain and fracture gap motion were measured by testing various configurations of entire fixation constructs on artificial bone (Canevasit) in axial compression. The determined properties of the materials and interfaces assessed in these experiments were then implemented into FE models of entire fixation constructs with different fracture width and screw configurations. The FE-predicted implant surface strains and fracture gap motions were compared with the experimental results.

The simulated results of the different construct configurations correlated strongly with the experimentally measured fracture gap motions (R2>0.99) and plate surface strains (R2>0.95).

In a systematic approach, FE model validation was achieved successfully in terms of fracture gap motion and implant deformation, confirming trustworthiness for surgical education. These validated models are used in a novel online education tool OSapp (https://osapp.ch/) to illustrate and explain the biomechanical principles of fracture fixations in an interactive manner.
IMPACT OF BMP-1 MODULATION IN EARLY FRACTURE REPAIR
Authors: Kronenberg D. , Everding J. , Moali C. , Legoff S. , Stange R.
Published: July 2023

BMP-1 is the major procollagen-C-peptidase activating, besides fibrillar collagen types I-III, several enzymes and growth factors involved in the generation of extracellular matrix. This study investigated the effect of adding and inhibiting BMP-1 directly post fracture.

Standardised femoral fractures were stabilized by an intramedullary nail in 12 week-old female C57Bl/6J mice. We injected either 20 µL recombinant active BMP-1, activity buffer or the BMP-1 specific inhibitor “sizzled”. After 7, 14 and 28 days, mice were sacrificed. Femurs were dissected and paraffin slides were prepared. Callus composition was divided into soft tissue, mineralized and cartilaginous callus. Murine MC3T3 pre-osteoblastic cells were kept in culture adding BMP-1 and sizzled during osteoblastic differentiation. Putative cytotoxicity was determined using MTT-vitality assay. Cell calcification, collagen deposition, and BMP-2 and myostatin protein quantity were characterized.

Adding BMP-1 displayed a weak positive effect on the outcome. After 7 days, more mineralised callus was present, meanwhile the cartilaginous callus was apparently remodelled at higher rate. In the case of BMP-1 inhibition, we observed more cartilaginous callus, which may indicate reduced stability. In cell culture, we could observe a high interference with mineralisation capabilities depending on the stage of osteoblastic development when adding BMP-1 or inhibiting it. Addition and inhibition impaired myostatin (anti-osteogen) and BMP-2 (pro-osteogen) expression.

Interfering with BMP-1 homeostasis in this early stage of fracture repair seems to have rather negative effects. Inhibition apparently yields lower callus quality while the addition of BMP-1 does not significantly accelerate the healing outcome. Cell culture experiments show that BMP-1 application after 7 days of healing leads to higher collagen output but has no effect on mineralisation. This may suggest that BMP-1 application at a later time-point may lead to more pronounced beneficial effects on fracture repair.
NO KNEE OVERLOADING IN RATS WITH DESTABILIZATION OF THE MEDIAL MENISCUS: A STUDY BASED ON INTEGRATED MOTION CAPTURE DATA AND HIGH-THROUGHPUT MUSCULOSKELETAL WORKFLOW
Authors: Piet J. , Vancleef S. , Mielke F. , Van Nuffel M. , Orozco G. , Korhonen R.K. , Lories R. , Aerts P. , Van Wassenbergh S. , Jonkers I.
Published: July 2023

Altered mechanical loading is a widely suggested, but poorly understood potential cause of cartilage degeneration in osteoarthritis. In rodents, osteoarthritis is induced following destabilization of the medial meniscus (DMM). This study estimates knee kinematics and contact forces in rats with DMM to gain better insight into the specific mechanisms underlying disease development in this widely-used model.

Unilateral knee surgery was performed in adult male Sprague-Dawley rats (n=5 with DMM, n=5 with sham surgery). Radio-opaque beads were implanted on their femur and tibia. 8 weeks following knee surgery, rat gait was recorded using the 3D²YMOX setup (Sanctorum et al. 2019, simultaneous acquisition of biplanar XRay videos and ground reaction forces).

10 trials (1 per rat) were calibrated and processed in XMALab (Knörlein et al. 2016). Hindlimb bony landmarks were labeled on the XRay videos using transfer learning (Deeplabcut, Mathis et al. 2019; Laurence-Chasen et al. 2020).

A generic OpenSim musculoskeletal model of the rat hindlimb (Johnson et al. 2008) was adapted to include a 3-degree-of-freedom knee. Inverse kinematics, inverse dynamics, static optimization of muscle forces, and joint reaction analysis were performed.

In rats with DMM, knee adduction was lower compared to sham surgery. Ground reaction forces were less variable with DMM, resulting in less variability in joint external moments. The mediolateral ground reaction force was lower, resulting in lower hip adduction moment, thus less force was produced by the rectus femoris. Rats with DMM tended to break rather than propel, resulting in lower hip flexion moment, thus less force was produced by the semimembranosus. These results are consistent with lower knee contact forces in the anteroposterior and axial directions.

These preliminary data indicate no overloading of the knee joint in rats with DMM, compared with sham surgery. We are currently expanding our workflow to finite element analysis, to examine mechanical cues in the cartilage of these rats (Fig1G).
SMALL MAGNESIUM CYLINDERS SIGNIFICANTLY INCREASE BONE VOLUME AND TRABECULAR THICKNESS WITH CONSTANT DENSITY AFTER IMPLANTATION IN THE SUBCHONDRAL BONE PLATE IN OSTEOARTHRITIC RABBITS: A PILOT STUDY
Authors: Angrisani N. , Willumeit-Römer R. , Windhagen H. , Scheper V. , Wiese B. , Mavila B. , Helmholz H. , Reifenrath J.
Published: July 2023

There is no optimal therapy to stop or cure chondral degeneration in osteoarthritis (OA). Beside cartilage, subchondral bone is involved. The often sclerotic bone is mechanically less solid which in turn influences negatively chondral quality. Microfracturing as therapeutic technique aims to enhance bone quality but is applied only in smaller cartilage lesions. The osteoproliferative properties of Magnesium (Mg) have been shown repeatedly1-3. The present study examined the influence of micro-scaled Mg cylinders compared to sole drilling in an OA model.

Ten New Zealand White rabbits underwent anterior crucial ligament transection. During 12 weeks after surgery, the animals developed OA as previously described4. In a second surgery, half of the animals received 20 drill holes (ø 0.5mm) and the other half received 20 drill holes, which were additionally filled with one Mg cylinder each. Extracapsular plication was performed in all animals. During the follow-up of 8 weeks three µ-computed tomographic (µCT) scans were performed: immediately after surgery and after four and eight weeks. Changes of bone volume, trabecular thickness and bone density were calculated and compared.

µCT evaluation showed an increase in bone volume and trabecular thickness in both groups. This increase was significantly higher in rabbits which received Mg cylinders showing thrice as high values for both parameters (bone volume: Mg group +44.5%, drilling group +15.1%, p≤0.025; trabecular thickness: Mg group +53.2%, drilling group +16.9%, p≤0.025). Also bone density increased in both groups, but on a distinctly lower level and with no significant difference.

Although profound higher bone volume was found after implantation of Mg cylinders, µCT showed similar levels of bone density indicating adequate bone quality in this OA model. Macroscopic and histological evaluation of cartilage condition have to reveal possible impact on OA progression. Additionally, current examination implement different alloys and influence on lameness.
THE DIFFERENCE IN BONE MINERAL DENSITY BETWEEN EXTRACTION SITE PRESERVATION AND AUTOLOGOUS HEALING WAS ANALYZED BY GRAY VALUE
Authors: Sun Y.
Published: July 2023

To analyze the effect of tooth extraction site preservation on bone mineral density 6 months after surgery.

From 2020 to 2021, two adjacent teeth (37, 38) of the same patient were extracted at the same time, and then 37 were selected for site preservation, implanted with Bio-oss bone powder, covered with double Bio-gide membrane, reduce tension and sutured. After 6 months of self-healing, 38 was taken CBCT, and the gray value measurement tool in the software was used to measure the bone mineral density of 37 bone graft areas and 38 extraction sockets.

Bone density was high in the center of the bone graft area after the extraction site, and the density decreased in the adjacent alveolar socket, but the gray value was still higher than 38 for natural healing.

Extraction site surgery can improve bone mass and quality at the extraction site. It is good for implanting.
CHARACTERIZATION OF NATIVE AND DECELLULARIZED PORCINE TENDON UNDER TENSION AND COMPRESSION: A CLOSER LOOK AT GLYCOSAMINOGLYCAN CONTRIBUTION TO TENDON MECHANICS
Authors: Solis J. , Edwards J.H. , Fermor H. , Riches P. , Brockett C. , Herbert A.
Published: July 2023

Decellularised porcine superflexor tendon (pSFT) has been demonstrated to be a suitable scaffold for anterior cruciate ligament reconstruction[1]. While the role of collagen in tendons is well known, the mechanical role of glycosaminoglycans (GAGs) is less clear and may be altered by the decellularisation process.

To determine the effects of decellularisation on pSFT GAG content and mechanical function and to investigate the consequences of GAG loss in tensile and compressive loading.

pSFTs were decellularised following previous techniques [2]. For GAG removal, native pSFTs were treated with chondroitinase ABC (ChABC; 0.1U/mL, 72h). Cell and GAG removal was validated using histology and quantitative assays. Native, decellularised and ChABC treated groups (n=6) were biomechanically characterised. In tension, specimens underwent stress relaxation and strength testing using previous protocols [1]. Stress relaxation data was fitted to a modified Maxwell-Weichert model to determine time-dependent (E1 & E2) and time-independent moduli (E0). The toe and linear region moduli (Etoe, Elinear), in addition to tensile strength (UTS) and failure strain were determined from strength testing. In compression, specimens underwent confined loading conditions (ramp at 10 s-1 to 10% strain and hold). The aggregate modulus (HA) and zero-strain permeability (k0) were determined using previous techniques [3]. Data was analysed by one-way ANOVA with Tukey post-hoc test to determine significant differences between test groups (p<0.05).

Quantitative assays showed no GAG reduction post-decellularisation, but a significant reduction after ChABC treatment. HA was only significantly reduced in the ChABC group. k0 was significantly higher for the ChABC group compared to decellularised. E0 was significantly reduced in the decellularised group compared to native and ChABC groups, while E1 and E2 were not different between groups. Etoe, Elinear, UTS and failure strain were not different between groups.

Decellularisation does not affect GAG content or impair mechanical function in pSFT. GAG loss adversely affects pSFT compressive properties, revealing major mechanical contribution under compression, but no significant role under tension.
MECHANICAL PROPERTIES AND WEAR RESISTANCE OF A VITAMIN E-BLENDED AND MODERATELY CROSSLINKED POLYETHYLENE FOR TOTAL KNEE ARTHROPLASTY
Authors: Puente Reyna A.L. , Schwiesau Jens , Altermann B. , Grupp T.M.
Published: July 2023

The purpose of the study was to compare the mechanical properties, oxidation and wear resistance of a vitamin E blended and moderately crosslinked polyethylene for total knee arthroplasty (MXE) in comparison with clinically established polyethylene materials.

The following polyethylene materials were tested: CPE (30 kGy e-beam sterilized), XLPE (75 kGy gamma crosslinked @ 100°C), ViXLPE (0.1 % vitamin E blended, 80 kGy e-beam crosslinked @ 100°C), and MXE (0.1 % vitamin E blended polyethylene, 30 kGy gamma sterilized). For the different tests, the polyethylene materials were either unaged or artificially aged for two or six weeks according to ASTM F2003-02.

The oxidation index was measured based on ASTM F2102 at a 1 mm depth. Small punch testing was performed based on ASTM F2977. Mechanical properties were measured on unaged materials according to ASTM D638.

Wear simulation was performed on a load controlled 3 + 1 station knee wear simulator (EndoLab GmbH, Thansau, Germany) capable of reproducing loads and movement of highly demanding activities (HDA) as well as ISO 14243-1 load profiles. The load profiles were applied for 5 million cycles (mc) or delamination of the polyethylene components. Medium size AS e.motion® PS Pro (Aesculap AG, Tuttlingen, Germany) femoral and tibial components with a ZrN-multilayer surface, as well as Columbus® CR cobalt-chrome alloy femoral and tibial components were tested. Particle analysis was performed on the serum samples of the ISO 14243-1 wear simulations based on ISO 17853:2011 and ASTM F1877.

The analysis of the mechanical properties show that moderately crosslinked polyethylene (MXE) might be a superior material for total knee arthroplasty applications [Schwiesau et al. 2021]. The addition of vitamin E in a moderately crosslinked polyethylene prevented its oxidation, kept its mechanical characteristics, and maintained a low wear, even under a HDA knee wear simulation.