bluuebunny/crossref_metadata_2025 huggingface dataset:
CLINICAL EFFECTIVENESS OF TENOTOMY VERSUS TENODESIS FOR LONG HEAD OF BICEPS TENDON PATHOLOGY: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Hartland A. , Islam R. , Teoh K.H. , Rashid M.
Published: July 2023

There remains much debate regarding the optimal method for surgical management of patients with long head of biceps pathology. The aim of this study was to compare the outcomes of tenotomy versus tenodesis.

This systematic review and meta-analysis was registered on PROSPERO (ref: CRD42020198658). Electronic databases searched included EMBASE, Medline, PsycINFO, and Cochrane Library. Randomized controlled trials (RCTs) comparing tenotomy versus tenodesis were included. Risk of bias within studies was assessed using the Cochrane risk of bias v2.0 tool and the Jadad score. The primary outcome included patient reported functional outcome measures pooled using standardized mean difference (SMD) and a random effects model. Secondary outcome measures included pain (visual analogue scale VAS), rate of Popeye deformity, and operative time.

860 patients from 11 RCTs (426 tenotomy vs 434 tenodesis) were included in the meta-analysis. Pooled analysis of all PROMs data demonstrated comparable outcomes between tenotomy vs tenodesis (SMD 0.14, 95% CI −0.04 to 0.32; p=0.13). Sensitivity analysis comparing RCTs involving patients with and without an intact rotator cuff did not change the primary outcome. There was no significant difference for pain (VAS). Tenodesis resulted in a lower rate of Popeye deformity (OR 0.29, 95% CI 0.19 to 0.45, p < 0.00001). Tenotomy demonstrated a shorter operative time (MD 15.21, 95% CI 1.06 to 29.36, p < 0.00001).

Aside from a lower rate of cosmetic deformity, tenodesis yielded no measurable significant benefit to tenotomy for addressing pathology in the long head of biceps. A large multi-centre clinical effectiveness randomised controlled trial is needed to provide clarity in this area.
THE ROLE OF DENTIN MATRIX PROTEIN 1 (DMP1) IN LIPUS-ACCELERATED OSTEOPOROTIC FRACTURE HEALING
Authors: Li M.C.M. , Chow S.K.H. , Wong R.M.Y. , Cheung W.H.
Published: July 2023

Osteoporotic fracture has become a major problem in ageing population and often requires prolonged healing time. Low Intensity Pulsed Ultrasound (LIPUS) can significantly enhance fracture healing through alteration of osteocyte lacuno-canalicular network (LCN). DMP1 in osteocytes is responsible for maintaining LCN and mineralisation. This study aims to investigate osteocyte-specific DMP1's role in enhanced osteoporotic fracture healing in response to mechanical stimulation.

Bilateral ovariectomy was performed in 6-month-old female SD rats to induce osteoporosis. Metaphyseal fracture was created at left distal femur using oscillating micro-saw. Rats were randomised to groups: (1) DMP1 KD, (2) DMP1 KD + LIPUS, (3) Control, or (4) Control + LIPUS, where KD stands for knockdown by injection of shRNA into marrow cavity 2 weeks before surgery. Assessments included weekly radiography, microCT and immunohistochemistry on DMP1, E11, FGF23 and sclerostin.

DMP1 KD significantly impaired LIPUS-accelerated fracture healing when comparing KD + LIPUS group to Control + LIPUS group. The X-ray relative opacity showed less tissue growth at all timepoints (Week 1, 3 & 6; p=0.000, 0.001 and 0.003 respectively) and the bone volume fraction was decreased after DMP1 KD at Week 3 (p=0.006). DMP1 KD also significantly altered the expression levels of osteocyte-specific DMP1, E11, FGF23 and sclerostin during healing process.

The lower relative opacity and bone volume fraction in DMP1 KD groups indicated that knockdown of DMP1 was associated with poorer fracture healing process compared to non-knockdown groups. The similar results between knockdown group with and without LIPUS showed that blockage of DMP1 would negate LIPUS-induced enhancement on fracture healing.

Acknowledgment: General Research Fund (Ref: 14113018)
THE OUTCOMES OF A LEARNED CLASSIFICATION MODEL CAN BE USED TO DETERMINE FUNCTIONAL STATUS POST TOTAL KNEE ARTHROPLASTY (TKA) BASED ON WEARABLE SENSOR DATA
Authors: Emmerzaal J. , De Brabandere A. , van der Straaten R. , Bellemans J. , De Baets L. , Davis J. , Jonkers I. , Timmermans A. , Vanwanseele B.
Published: July 2023

In a clinical setting, there is a need for simple gait kinematic measurements to facilitate objective unobtrusive patient monitoring. The objective of this study is to determine if a learned classification model's output can be used to monitor a person's recovery status post-TKA.

The gait kinematics of 20 asymptomatic and 17 people with TKA were measured using a full-body Xsens model1. The experimental group was measured at 6 weeks, 3, 6, and 12 months post-surgery. Joint angles of the ankle, knee, hip, and spine per stride (10 strides) were extracted from the Xsens software (MVN Awinda studio 4.4)1.

Statistical features for each subject at each evaluation moment were derived from the kinematic time-series data. We normalised the features using standard scaling2. We trained a logistic regression (LR) model using L1-regularisation on the 6 weeks post-surgery data2–4.

After training, we applied the trained LR- model to the normalised features computed for the subsequent timepoints. The model returns a score between 0 (100% confident the person is an asymptomatic control) and 1 (100% confident this person is a patient). The decision boundary is set at 0.5.

The classification accuracy of our LR-model was 94.58%. Our population's probability of belonging to the patient class decreases over time. At 12 months post-TKA, 38% of our patients were classified as asymptomatic.
STUDY OF SILK STRAIN AND ITS PREPARATION FOR MENISCUS TISSUE ENGINEERING SCAFFOLD
Authors: Numpaisal P. , Khatsee S. , Arunsan P. , Ruksakulpiwat Y.
Published: July 2023

Silk fibroin (SF) has been used as a scaffold for cartilage tissue engineering. Different silkworms strain produced different protein. Also, molecular weight of SF depends on extraction method. We hypothesised that strain of silkworm and method of SF extraction would effect biological properties of SF scaffold. Therefore, cell viability and chondrogenic gene expression of human chondrogenic progenitor cells (HCPCs) treated with SF from 10 silkworm strains and two common SF extraction methods were investigate in this study.

Twenty g of 10 strains silk cocoons were separately degummed in 0.02M Na2CO3 solution and dissolved in 100๐C for 30 minutes. Half of them were then dissolved in CaCl2/Ethanol/H2O [1:2:8 molar ratio] at 70±5๐C (method 1) and other half was dissolved in 46% w/v CaCl2 at 105±5๐C (method 2) for 4 hours. HCPCs were cultured in SF added cultured medial according to strain and extraction method. Cell viability at day 1, 3, and 7, were determined. Expression of collagen I, collagen II, and aggrecan at day 7 and 14, was studied. All experiment were done in triplicated samples.

Generally, method 1 SF extraction showed higher cell viability in all strains. Cell viability from Nanglai Saraburi, Laung Saraburi and Nangtui strains were higher than those without SF in every time point while Wanasawan and J108 had higher viability at day 1 and decreased by time. Expression in collagen 1, collagen 2 and aggrecan in method 1 are higher at day 7 and day 14. Collagen 1 expression was highest in Nangnoi Srisaket, followed by Laung Saraburi and Nanglai Saraburi in day 7. Nangnoi Srisaket also had highest expression at day 14, followed by Nanglai Saraburi and Laung Saraburi respectively. Nangseaw had highest collagen 2 expression, follow by Laung Saraburi and Nangnoi Srisaket respectively. Higher aggrecan gene expression of Tubtimsiam, Wanasawan, UB 1 and Nangnoi Srisaket was observed at day 7 and increased expression of all strains at day 14.

SF extraction using CaCl2/Ethanol/H2O offered better cell viability and chondrogenic expression. Nangseaw, Laung Saraburi and Nangnoi Srisaket strains expressed more chondrogenic phenotype.
TETRAHEDRAL AMORPHOUS CARBON COATING FOR KNEE JOINT APPLICATION AND ITS TRIBOLOGICAL PERFORMANCE
Authors: Voropai V. , Nieher M. , Kratsch A. , Kirchner W. , Giggel B. , Lohmann C.H. , Bertrand J. , Weißmantel S. , Döring J.
Published: July 2023

Total knee arthroplasty is one of the most common surgeries. About 92% of all implanted knee endorposthesis in 2020 were manufactured from uncoated CoCrMo articulating on ultra-high-molecular-weight polyethylene. All articluations generate wear particles and subsequent emission of metal ions due to the mechanical loading. These wear particles cause diverse negative reactions in the surrounding tissues and can lead to implant loosening. Coating technologies might offer the possibility to reduce this wear. Therefore, we investigated the applicability of tetrahedral amorphous carbon (ta-C) coating on CoCrMo alloy.

Polished specimens made of CoCrMo wrought alloy according to ISO 5832-12 were coated with ta-C coatings with different layer structure using pulsed laser deposition (PLD). This process allows the deposition of ta-C coatings with low internal stress using an additional relaxation laser. Surface quality and mechanical properties of the coating were characterised using optical surface measurements (NanoFocus μsurf expert, NanoFocus AG) and a nanoindentation tester NHT3 (Anton Paar GmbH). Scratch tests were performed on Micro Scratch Tester MST3 (Anton Paar TriTec SA) to define the coating adhesion. Pin-on-plate tribological tests, with a polyethylene ball sliding on the ta-C-coated plate under a defined load according to ISO 14243-1 were performed using a linear tribometer (Anton Paar GmbH) to evaluate the tribological and wear properties.

The ta-C coatings showed a mean roughness Ra of 5-20 nm and a hardness up to 60 GPa (n=3). The adhesion of the ta-C coatings (n=3) was comparable to the commercial coatings like TiN and TiNbN. The pin-on-plate tests showed an improvement of tribological properties in comparison with the polished uncoated CoCrMo specimens (n=3).

The ta-C coatings applied by DLP technology show increased hardness compared to the base material and sufficient adhesion. Further research will be needed to investigate the optimal coating strategy for implant coating.
IN VIVO LIGAMENTOGENESIS IN EMBROIDERED POLY(LACTIC-CO-Ε-CAPROLACTONE) / POLYLACTIC ACID SCAFFOLDS FUNCTIONALIZED BY FLUORINATION AND HEXAMETHYLENE DIISOCYANATE CROSS-LINKED COLLAGEN FOAMS
Authors: Kokozidou M. , Gögele C. , Pirrung F. , Hammer N. , Werner C. , Kohl B. , Hahn J. , Breier A. , Schöpfer M. , Meyer M. , Schulze-Tanzil G.
Published: July 2023

Although autografts represent the gold standard for anterior cruciate ligament (ACL) reconstruction, tissue-engineered ACLs provide a prospect to minimize donor site morbidity and limited graft availability. This given study characterizes the ligamentogenesis in embroidered poly(L-lactide-co-ε-caprolactone) (P(LA-CL)) / polylactic acid (PLA) constructs using a dynamic nude mice xenograft model. (P(LA-CL))/PLA scaffolds remained either untreated (co) or were functionalized by gas fluorination (F), collagen foam cross-linked with hexamethylene diisocyanate (HMDI) (coll), or gas fluorination combined with the foam (F+coll). Cell free constructs or those seeded for 1 week with lapine ACL ligamentocytes were implanted into nude mice for 12 weeks. Following explantation, biomechanical properties, cell vitality and content, histopathology of scaffolds (including organs: liver, kidney, spleen), sulphated glycosaminoglycan (sGAG) contents and biomechanical properties were assessed.

Implantation of the scaffolds did not negatively affect mice weight development and organs, indicating biocompatibility. All scaffolds maintained their size and shape for the duration of the implantation. A high cell viability was detected in the scaffolds prior to and following implantation. Coll or F+coll scaffolds seeded with cells yielded superior macroscopic properties when compared to the controls. Mild signs of inflammation (foreign-body giant cells, hyperemia) were limited to scaffolds without collagen. Microscopical score values and sGAG content did not differ significantly. Although remaining stable in vivo, elastic modulus, maximum force, tensile strength and strain at Fmax were significantly lower in the in vivo compared to the samples cultured 1 week in vitro, but did not differ between scaffold subtypes, except for a higher maximum force in F+coll compared with F samples (in vivo). Scaffold functionalization with fluorinated collagen foam provides a promising approach for ACL tissue engineering.

(shared first authorship)

Acknowledgement: The study was supported by DFG grants SCHU1979/9-1 and SCHU1979/14-1.
COMPARISON OF BONE ANCHOR MATERIALS IN AN ANATOMICALLY RELEVANT IN VITRO MODEL OF THE BONE-TENDON INTERFACE
Authors: Loukopoulou C. , Vorstius J. , Paxton J.
Published: July 2023

To ensure clinical relevance, the in vitro engineering of tissues for implantation requires artificial replacements to possess properties similar to native anatomy. Our overarching study is focussed on developing a bespoke bone-tendon in vitro model replicating the anatomy at the flexor digitorum profundus (FDP) tendon insertion site at the distal phalanx. Anatomical morphometric analysis has guided FDP tendon model design consisting of hard and soft tissue types. Here, we investigate potential materials for creation of the model's bone portion by comparison of two bone cements; brushite and genex (Biocomposites Ltd).

3D printed molds were prepared based on anatomical morphometric analysis of the FDP tendon insertion site and used to cast identical bone blocks from brushite and genex cements. Studies assessing the suitability of each cement type were conducted e.g. setting times, pH on submersion in culture medium and interaction with fibrin gels. Data was collected using qualitative imaging and qualitative measurements (N=3,n=6) for experimental conditions.

Both brushite (BC) and genex (GC) cements could be cast into bespoke molds, producing individual blocks and were mixed/handled with appropriate setting times. On initial submersion in culture medium, BC caused a reduction in pH values (7.49 [control]) to 6.85) while GC remained stable (7.59). Reduction in pH value also affected fibrin gel interaction where gel was seen to be detaching/not forming around BC and medium discolouration was noted. This was not observed in GC. While GC outperformed BC in initial tests, repeated washing of BC led to pH stabilisation (7.5,3xwashes), consistent with their further use in this model.

This study has compared BC and GC as materials for bone block production. Both materials show promise, and current work assessing material properties and cell proliferation are needed to inform our choice for use in our FDP-tendon-bone interface model.

This research was supported by an ORUK Studentship award (ref:533). Genex was kindly provided by Biocomposites, Ltd.
A NEW REMOTE METHOD FOR ASSESSING ANKLE RANGE OF MOTION USING A SMARTPHONE: THE DIJIA APP
Authors: ÇİL E.T. , Subaşı F. , Gökçek G.G. , Şerif T. , Şaylı U.
Published: July 2023

Recently, several smartphone applications (apps) have been developed and validated for ankle ROM measurement tools like the universal goniometer. This is the first innovative study introduces a new smartphone application to measure ankle joint ROM as a remote solution. This study aimed to assess the correlation between smartphone ROM and universal goniometer measurements, and also report the evaluation of the DijiA app by users.

The study included 22 healthy university students (14F/8M; 20.68±1.72 years) admitted to Yeditepe University. Fourty four feet was measured by both the universal goniometer (UG) and DijiA app. The datas were analyzed through using the intraclass correlation coefficient (ICC). The DijiA app was evaluated by usability testing with representative users.

Pearson correlation coefficient test showed moderate correlation between the DijiA and UG for dorsiflexion (DF) and plantar flexion (PF) measurements (Pearson correlation coefficient: r=0.323, for DF; r=0.435 for PF 95% confidence interval). The application usability was found as high with 76.5 average score and users liked it.

The DijiA app may be a more convenient and easy way to measure ankle DF and PF-ROM than UG. It can be used to evaluate ROM in clinical practice or home using as a personal smartphone.
IS MULLIGAN CONCEPT EFFECTIVE TREATMENT FOR CHRONIC PLANTAR FASCIITIS? A RANDOMIZED CONTROLLED TRIAL
Authors: Çil E.T. , Subaşı F. , Şaylı U.
Published: July 2023

Plantar fasciitis (PF) is one of the widespread conditions causing hindfoot pain. The most common presenting symptoms are functional limitation and pain (first step and activity) on plantar surface of the foot. The non-operative treatments provide complete resolution of pain in 90% of patients, but functional limitation still remains as a risk factor for recurrency of PF. Although the number of non-operative treatment options showing efficacy on pain and functional limitation are excessive, the evidences are limited for functional limitation. Additionally, Mulligan mobilization with movement (MMWM) in Chronic Plantar Fasciitis has been poorly studied in the literature. According to these findings, the study was aimed to determine effectiveness of Mulligan mobilization with movement on Chronic Plantar Fasciitis.

A total of 25 patients (40 feet) with chronic PF were included in the study. The patients were randomly divided into Mulligan concept rehabilitation group (PF-M, n=20 feet) and Home Rehabilitation group (PF-H, n=20 feet). (MMWM), Foot and ankle exercises program were applied to PF-M, twice a week totally 8 week (16 sessions) and foot- ankle exercises as a home program were given for PF-H, 8 weeks. The range of motion (ROM) for dorsiflexion and plantar flexion was measured by using a manual goniometer. Pain, disability and activity restriction were assessed by Foot Function Index (FFI) . The first step morning pain was evaluated by Visual Analogue Scale (VAS) and Kinesiophobia was also reported by using Tampa Scale (TSK). Patients were evaluated at baseline and 8 weeks.

FFI, VAS, TSK, ROM values improved in all groups (intragroup variability) at 8th week (P < .05). The other result indicated that ROM values for DF and PF and TSK scores in PF-M had more significant improvement than PF-H (p<.05).

To the best of our knowledge this is the first randomised controlled trial for investigating Mulligan Concept efficiancy on chronic PF. Both Mulligan mobilization with movement (MMWM) and exercise protocols are effective for chronic PF. Furthermore, The Mulligan concept seems more effective treatment option in reducing kinesiophobia and improving functional capacity.
PAIN MANAGEMENT IN POSTOPERATIVE TOTAL KNEE ARTHROPLASTY IN EPIDURAL BUPIVACAINE INJECTION VERSUS INTRA-ARTICULAR INJECTION
Authors: Kale S. , Mehra S. , Bhor P. , Gunjotikar A. , Dhar S. , Singh S.
Published: July 2023

Total Knee Arthroplasty (TKA) improves the quality of life of osteoarthritic and rheumatoid arthritis patients, however, is associated with moderate to severe postoperative pain. There are multiple methods of managing postoperative pain that include epidural anesthesia but it prevents early mobilization and results in postoperative hypotension and spinal infection. Controlling local pain pathways through intra-articular administration of analgesics is a novel method and is inexpensive and simple. Hence, we assess the effects of postoperative epidural bupivacaine injection along with intra-articular injection in total knee replacement patients.

The methodology included 100 patients undergoing TKA randomly divided into two groups, one administered with only epidural bupivacaine injection and the other with intra-articular cocktail injection. The results were measured based on a 10-point pain assessment scale, knee's range of motion (ROM), and Lysholm knee score.

The VAS score was lower in the intra-articular cocktail group compared to the bupivacaine injection group until the end of 1-week post-administration (p<0.01). Among inter-group comparisons, we observed that the range of motion was significantly more in cocktail injection as compared to the bupivacaine group till the end of one week (p<0.05). Lysholm's score was significantly more in cocktail injection as compared to the bupivacaine group till the end of one week (p<0.05).

Our study showed that both epidural bupivacaine injection and intra-articular injection were effective in reducing pain after TKA and have a comparable functional outcome at the end of 4 weeks follow up. However, the pain relief was faster in cases with intra-articular injection, providing the opportunity for early rehabilitation. Thus, we recommend the use of intra-articular cocktail injection for postoperative management of pain after total knee arthroplasty, which enables early rehabilitation and faster functional recovery of these patients.
MIR-92A/KLF4/P110Δ REGULATES TITANIUM PARTICLE-INDUCED MACROPHAGE INFLAMMATION AND OSTEOLYSIS
Authors: Wen Z. , Ding Y. , Lin S. , Li C. , Ouyang Z.
Published: July 2023

As peri-prosthetic aseptic loosening is one of the main causes of implant failure, inhibiting wear particles induced macrophages inflammation is considered as a promising therapy for AL to expand the lifespan of implant. Here, we aim at exploring the role of p110δ, a member of class IA PI3K family, and Krüppel-like factor 4 (KLF4) in titanium particles (TiPs) induced macrophages-inflammation and osteolysis.

Firstly, IC87114, the inhibitor of p110δ and siRNA targeting p110δ were applied and experiments including ELISA and immunofluorescence assay were conducted to explore the role of p110δ. Sequentially, KLF4 was predicted as the transcription factor of p110δ and the relation was confirmed by dual luciferase reporter assay. Next, assays including RT-PCR, western blotting and flow cytometry were performed to ensure the specific role of KLF4. Finally, TiPs-induced mice cranial osteolysis model was established, and micro-CT scanning and immunohistochemistry assay were performed to reveal the role of p110δ and KLF4 in vivo.

Here, we found that p110δ was upregulated in TiPs-stimulated macrophages. The inhibition of p110δ or knockdown of p110δ could significantly dampen the TiPs-induced secretion of TNFα and IL-6. Further mechanistic studies confirmed that p110δ was responsible for TNFα and IL-6 trafficking out of Golgi complex without affecting their expression in TiPs-treated macrophages. Additionally, we explored the upstream regulators and confirmed that Krüppel-like factor 4 (KLF4) was the transcription repressor of p110δ. Apart from that, KLF4, targeted by miR-92a, could also attenuate TiPs-induced inflammation by mediating NF-κB pathway and M1/M2 polarization. By the establishment of TiPs-induced mice cranial osteolysis model, we found that KLF4 knockdown exacerbated TiPs-induced osteolysis which was strikingly ameliorated by knockdown of p110δ.

In summary, our study suggests the key role of miR-92a/KLF4/p110δ signal in TiPs-induced macrophages inflammation and osteolysis.
NEUROMUSCULAR ELECTRICAL STIMULATION IS BENEFICIAL FOR EARLY REHABILITATION AFTER ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION
Authors: Du L. , Yang B. , Zhong Z. , Wu K.
Published: July 2023

The principal of “function priority, early rehabilitation, and return to sports” is now the goal for sports injury rehabilitation. Neuromuscular electrical stimulation for anterior cruciate ligament (ACL) reconstruction is a rising procedure for early rehabilitation. This paper systematically assessed the effects of neuromuscular electrical stimulation on postoperative ACL reconstruction to provide guidance for physiotherapist and patient when designing a suitable rehabilitation protocol.

To evaluate the interventional outcomes of neuromuscular electrical stimulation following ACL reconstruction, we searched PubMed, EMbase, the Cochrane Library, Web of Science and CNKI to collect all randomized controlled trials (RCTs) comparing the effects with neuromuscular electrical stimulation and without intervention on rehabilitation after ACL reconstruction up to January 30, 2022. Two investigators independently performed literature screening, data extraction, bias assessment of risk, and used RevMan 5.3 software to conduct a meta-analysis.

A total of six RCTs were included, and the results showed that the use of neuromuscular electrical stimulation after anterior cruciate ligament reconstruction significantly improved the International Knee Documentation Committee (IKDC) scores (MD 6.33, 95% CI [-0.43, 12.22]; I2 = 66%; p = 0.040), the Lysholm score (MD 7.94, 95% CI [6.49, 9.39]; I2 = 89%; p < 0.001), and the range of motion (ROM) (MD 9.99, 95% CI [7.97, 12.02]; I2 = 81%; p < 0.001) in the knees when compared to the control group without using neuromuscular electrical stimulation.

Existing evidence show that neuromuscular electrical stimulation is beneficial for early rehabilitation after ACL reconstruction. The use of neuromuscular electrical stimulation is encouraged in the design of rehabilitation protocol. However, due to the limited number of RCT studies and the small sample size, further multi-center RCTs with more participants are needed for a higher-level evidence.
THE EARLY FAILURE OF ROTATOR CUFF REPAIRS: A SYSTEMATIC REVIEW
Authors: Joumah A. , Cowling P.
Published: July 2023

Though retear rates following rotator cuff repair are well established, we set out to review current literature to determine when early retears occurred (defined as <12m following surgery), and examine which pre- and post-operative variables might affect outcome.

Pubmed, Medline, and CINAHL were searched for literature published from 2011 to 2021 using specific search terms. The inclusion criteria were studies reporting retear rates within 12 months of initial surgical repair. Exclusionary criteria were studies that included partial thickness tears, and studies that did not use imaging modalities within 12 months to assess for retears. PRISMA guidelines were followed, identifying a total of 10 papers.

A combined total of 3372 shoulders included (Mean age 56 −67 years). The most common modality used to identify early retears were ultrasound scan and MRI. 6 of the 10 studies completed imaging at 0-3 months, 6 studies imaged at 3-6 months and 6 studies imaged at 6-12 months. Across all studies, there was a 17% early retear rate (574 patients). Of these, 13% occurred by 3 months, whilst the peak for retears occurred at 3-6 months (82%) and 5% occurred at 6-12 months. The risk of retear was higher in larger tears and extensive tendon degeneration. All studies apart from one documented a return to work/sport at 6 months post-operatively. Postoperative rehabilitation does not appear to alter retear rate, although data is limited with only 1 of 10 studies allowing active range of movement before 6 weeks. Retorn tendons had poorer functional outcomes compared to intact tendons at 12m following initial repair.

The majority of early retears occur at 3-6 months and this time period should be prioritised both in rehabilitation protocols and future research. Age, tear size, and tendon degeneration were found to influence likelihood of early retears.
A NOVEL 3D-PRINTED HYDROXYAPATITE/ARAGONITE BIODEGRADABLE BONE GRAFT SUBSTITUTE FOR BONE REGENERATION
Authors: Shi Y. , Deganello D. , Xia Z.
Published: July 2023

Bone defects require implantable graft substitutes, especially porous and biodegradable biomaterial for tissue regeneration. The aim of this study was to fabricate and assess a 3D-printed biodegradable hydroxyapatite/calcium carbonate scaffold for bone regeneration.

Materials and methods:

A 3D-printed biodegradable biomaterial containing calcium phosphate and aragonite (calcium carbonate) was fabricated using a Bioplotter. The physicochemical properties of the material were characterised. The materials were assessed in vitro for cytotoxicity and ostegenic potential and in vivo in rat intercondylar Φ3mm bone defect model for 3 months and Φ5mm of mini pig femoral bone defects for 6 months.

The results showed that the materials contained hydroxyapatite and calcium carbonate, with the compression strength of 2.49± 0.2 MPa, pore size of 300.00 ± 41mm, and porosity of 40.±3%. The hydroxyapatite/aragonite was not cytotoxic and it promoted osteogenic differentiation of human umbilical cord matrix mesenchymal stem cells in vitro. After implantation, the bone defects were healed in the treatment group whereas the defect of controlled group with gelatin sponge implantation remained non-union. hydroxyapatite/aragonite fully integrated with host bone tissue and bridged the defects in 2 months, and significant biodegradation was followed by host new bone formation. After implantation into Φ5mm femoral defects in mini pigs hydroxyapatite/aragonite were completed degraded in 6 months and fully replaced by host bone formation, which matched the healing and degradation of porcine allogenic bone graft.

In conclusion, hydroxyapatite/aragonite is a suitable new scaffold for bone regeneration. The calcium carbonate in the materials may have played an important role in osteogenesis and material biodegradation.
PATTERN OF RECOVERY AND MANAGEMENT STRATEGIES OF WORKERS WITH MENISCUS AND LIGAMENTOUS KNEE INJURIES
Authors: Renteria C. , Wasserstein D. , Tomescu S. , Razmjou H.
Published: July 2023

The primary purpose of this longitudinal study was to examine the impact of physical and mental well-being on a successful return to work after cartilage or ligament knee injury. A secondary purpose was to examine the effectiveness of our program regarding ordering imaging (plain X-rays, US, MRI, CT scan), and the impact that costly investigations made in clinical management.

Workers who had sustained a work-related knee injury and were assessed at the lower extremity specialty clinic of our hospital program were followed up until they were discharged. All patients completed the numeric pain rating scale (NPRS), the Lower Extremity Functional Scale (LEFS), and the Hospital Anxiety and Depression Scale (HADS) on the initial assessment and at final follow-up.

We included 30 patients, mean age, 50(9), 11(37%) females, 19(63%) males. The most common mechanisms of injury were twisting (13, 45%) and falls (12, 41%). The knee injuries included 10 anterior collateral ligament (ACL), 3 posterior collateral ligament (PCL), 19 medical and lateral ligament injuries, and 22 meniscus injuries with some injuries overlapping. Ten patients (30%) underwent surgery (8 meniscectomy, two ligamentous repairs).

Patients showed improvement in pain scores (p<0.0001) and the LEFS scores (p=0.004). Seventeen patients (57%) returned to full-time work and 11 (37%) were not working at the time of discharge with one patient performing part-time work, and one on re-training. Higher levels of pre (p=0.02) and post-treatment (p=0.03) depression and post-treatment anxiety (p=0.02) had a negative impact on a successful return to work. Most clients had proper investigations ordered by their family physicians in the community (24 plain x-rays, 11 US, and 21 MRI). Our team ordered only 6 plain x-rays and 6 new MRI.

We found significant improvement in pain and disability in injured workers who received an expedited multidisciplinary care. Anxiety and depression were the most important predictors of poorer recovery and a less successful work status. The judicious use of costly imaging is expected to reduce the overall health care cost of an injury, while providing new important information such as adding a new diagnosis or changing the management.
A PROTOCOL TO EVALUATE AND VALIDATE IMPLANT INTERNAL FORCES AND MOMENTS
Authors: Mühling M. , Sandriesser S. , Augat P.
Published: July 2023

Implant manufacturers develop new products to improve existing fracture fixation methods or to approach new fracture challenges. New implants are commonly tested and approved with respect to their corresponding predecessor products, because the knowledge about the internal forces and moments acting on implants in the human body is unclear. The aim of this study was to evaluate and validate implant internal forces and moments of a complex physiological loading case and translate this to a standard medical device approval test.

A finite elements model for a transverse femur shaft fracture (AO/OTA type 32-B2) treated with a locked plate system (AxSOS 3 Ti Waisted Compression Plate Broad, Stryker, Kalamazoo, USA) was developed and experimentally validated. The fractured construct was physiologically loaded by resulting forces on the hip joint from previously measured in-vivo loading experiments (Bergmann et. al). The forces were reduced to a level where the material response in the construct remained linear elastic. Resulting forces, moments and stresses in the implant of the fractured model were analysed and compared to the manufacturers’ approval data.

The FE-model accurately predicted the behaviour of the whole construct and the micro motion of the working length of the osteosynthesis. The resulting moment reaction in the working length was 24 Nm at a load of 400 N on the hip. The maximum principle strains on the locking plate were predicted well and did not exceed 1 %.

In this study we presented a protocol by the example of locked plated femur shaft fracture to calculate and validate implant internal loading using finite element analysis of a complex loading. This might be a first step to move the basis of development of new implants from experience from previous products to calculation of mechanical behaviour of the implants and therefore, promote further optimization of the implants’ design.
THE IMPACT OF SEX ON BONE STRUCTURE AND ANGIOGENESIS IN SYNDECAN-1 DEFICIENT MICE
Authors: Timmen M. , Arras C. , Roters N. , Kronenberg D. , Bixel M.G. , Adams R.H. , Stange R.
Published: July 2023

Neoangiogenesis drives the replacement of mineralised cartilage by trabecular bone during bone growth regulated by molecules like e.g. VEGF, OPG and RANKL. The Heparan sulfate proteoglycan Syndecan-1 (Sdc1) plays a role in the interaction of osteoclasts and osteoblasts and the development of blood vessels. We expected Sdc1 to have an influence on bone structure and vessel development. Therefore, bone structure and angiogenesis at the growth plate in mice was compared and the influence of Syndecan-1 deficiency was characterised.

Animals: Femura of male and female C57BL/6 WT (5♀, 6♂) and Sdc1-/- (9♀, 5♂) mice were used for native bone analysis at 4 month age. Histology: Bone structure was analysed using microCT scans with a resolution of 9µm. Vascularisation was visualised using an anti-Endomucin antibody in 80µm thick cryosections. In vitro angiogenesis: Bone marrow isolates were used to generate endothelial progenitor cells by sequential cultivation on fibronectin. Microvessel development was analysed 4h after plating on matrigel.

Bone structure in male Sdc1 deficient mice was significantly reduced compare to male WT, whereas female mice of both genotypes did not differ. Sdc1 deficient mice at the age of 4 month showed a high decrease in the number of vessel bulbs at the chondro-osseous border (growth plate) compared to WT mice. However, no sex related differences were shown. Quantification of microvessel outgrowth of endothelial cells revealed a decreased amount of sprouting, but increased length of microvessels of Sdc1-/- cells compared to WT.

Syndecan-1 has a significant impact on neoangiogenesis at the chondro-osseous border of the native bone, but the impact of Syndecan-1 deficiency on the loss of bone structure was significantly higher in male mice. This emphasises the importance to further characterise the function of Syndecan-1 regulated processes during enchondral ossification in a sex dependent manner.
FUNCTIONAL OUTCOME FOLLOWING DIFFERENT SURGICAL APPROACHES FOR TIBIAL NAILING
Authors: Kröger I. , Pätzold R. , Brand A. , Wackerle H. , Klöpfer-Krämer I. , Augat P.
Published: July 2023

Tibial shaft fractures require surgical stabilization preferably by intramedullary nailing. However, patients often report functional limitations even years after the injury. This study investigates the influence of the surgical approach (transpatellar vs. parapatellar) on gait performance and patient reported outcome six months after surgery.

Twenty-two patients with tibial shaft fractures treated by intramedullary nailing through a transpatellar approach (TP: n=15, age 41±15, BMI 24±3) or a parapatellar approach (PP: n=7, age 34±15, BMI 23±2) and healthy, matched controls (n=22, age 39±13, BMI 24±2) were assessed by instrumented motion analysis six months after intramedullary nailing. Short musculoskeletal function assessment questionnaire (SMFA) as well as kinematic and kinetic gait data were collected during level walking. Comparisons among approach methods and control group were performed by analysis of variance and Mann-Whitney test.

Six months after surgery, knee kinetics in both groups differed significantly compared to controls (p <.04). The approach method affected gait speed (TP: p = .002; PP: p = .08) and knee kinematics in the early stance phase (TP: p = .011; PP: p = .082), with the parapatellar approach showing a more favorable outcome. However, the difference between patient groups was not significant for any of the assessed gait parameters (p > .2). Also, no differences could be found in the bother index (BI) or function index (FI) of SMFA between surgical approach methods (BI: TP: Mdn = 7.2, PP: Mdn = 9.4; FI: TP: Mdn = 10.3, PP: Mdn = 9.2, p > .7).

Our study demonstrates, that six months after surgery for tibial shaft fractures functional limitations remain. These limitations appear not to be different for either a trans- or a parapatellar approach for the insertion of the intramedullary nail. The findings of this study are limited by the relatively short follow up time period and small number of patients. Future studies should investigate the source of the functional limitation after intramedullary nailing of tibial shaft fractures.
NRF2 DEFICIENCY CONTRIBUTES TO AGE-DEPENDENT PROGRESSION OF FEMALE OSTEOPOROSIS
Authors: Tohidnezhad M. , Kubo Y. , Gonzalez J.A.H. , Weiler M. , Pahlavani H. , Szymanski K. , Mirazaali M.J. , Pufe T. , Jahr H.
Published: July 2023

Nuclear factor erythroid 2–related factor 2 (Nrf2) is a crucial transcription factor to maintain cellular redox homeostasis, but is also affecting bone metabolism. As the association between Nrf2 and osteoporosis in elderly females is not fully elucidated, our aim was to shed light on the potential contribution of Nrf2 to the development of age-dependent osteoporosis using a mouse model.

Female wild-type (WT, n=18) and Nrf2-knockout (KO, n=12) mice were sacrificed at different ages (12 weeks=young mature adult, and 90 weeks=old), morphological cortical and trabecular properties of femoral bone analyzed by micro-computed tomography (µCT), and compared to histochemistry. Mechanical properties were derived from quasi-static compression tests and digital image correlation (DIC) used to analyze full-field strain distribution. Bone resorbing cells and aromatase expression by osteocytes were evaluated immunohistochemically and empty osteocyte lacunae counted in cortical bone. Wilcoxon rank sum test was used for data comparison and differences considered statistically significant at p<0.05.

When compared to old WT mice, old Nrf2-KO mice revealed a significantly reduced trabecular bone mineral density (BMD), cortical thickness (Ct.Th), cortical area (Ct.Ar), and cortical bone fraction (Ct.Ar/Tt.Ar). Surprisingly, these parameters were not different in skeletally mature young adult mice. Metaphyseal trabeculae were thin but present in all old WT mice, while no trabecular bone was detectable in 60% of old KO mice. Occurrence of empty osteocyte lacunae did not differ between both groups, but a significantly higher number of osteoclast-like cells and fewer aromatase-positive osteocytes were found in old KO mice. Furthermore, female Nrf2-KO mice showed an age-dependently reduced fracture resilience when compared to age-matched WT mice.

Our results confirmed lower bone quantity and quality as well as an increased number of bone resorbing cells in old female Nrf2-KO mice. Additionally, aromatase expression in osteocytes of old Nrf2-KO mice was compromised, which may indicate a chronic lack of estrogen in bones of old Nrf2-deficient mice. Thus, chronic Nrf2 loss seems to contribute to age-dependent progression of female osteoporosis.
INSTRUMENTATION INACCURACIES STRONGLY INFLUENCE THE BIOMECHANICAL AND COMPUTATIONAL FAILURE RISK OF FRACTURE FIXATIONS
Authors: Mischler D. , Tenisch L. , Schader J.F. , Dauwe J. , Gueorguiev B. , Windolf M. , Varga P.
Published: July 2023

Despite past advances of implant technologies, complication rates of fixations remain high at challenging sites such as the proximal humerus [1]. These may not only be owed to the implant itself but also to dissatisfactory surgical execution of fracture reduction and implant positioning. Therefore, the aim of this study was to quantify the instrumentation accuracy of a highly standardised and guided procedure and its influence on the biomechanical outcome and predicted failure risk.

Preoperative planning of osteotomies creating an unstable 3-part fracture and fixation with a locking plate was performed based on CT scans of eight pairs of low-density proximal humerus samples from elderly female donors (85.2±5.4 years). 3D-printed subject-specific guides were used to osteotomise and instrument the samples according to the pre-OP plan. Instrumentation accuracies in terms of screw lengths and orientations were evaluated by comparing post-OP CT scans with the pre-OP plan. The fixation constructs were biomechanically tested until cyclic cut-out failure [2]. Failure risks of the planned and the post-OP configurations were predicted using a validated sample-specific finite element (FE) simulation approach [2] and correlated with the experimental outcomes.

Small deviations were found for the instrumented screw trajectories compared to the planned configuration in the proximal-distal (0.3±1.3º) and anterior-posterior directions (-1.7±1.8º), and for screw tip to joint distances (-0.3±1.1 mm). Significantly higher failure risk was predicted for the post-OP compared to the planned configurations (p<0.01) via FE. When incorporating the instrumentation inaccuracies, the biomechanical results could be predicted well with FE (R2=0.70).

Despite the high instrumentation accuracy achieved using sophisticated subject-specific 3D-printed guides, even minor deviations from the pre-OP plan significantly increased the FE-predicted risk of failure. This underlines the importance of intraoperative guiding technology [3] in tandem with careful pre-OP planning to assist surgeons to achieve optimal outcomes.

Acknowledgements

This study was performed with the assistance of the AO Foundation via the AOTRAUMA Network.
INTEGRIN A2B1 DEFICIENCY REVEALS FASTER REGENERATION THROUGH BMP PATHWAY ACTIVATION IN A MURINE FRACTURE HEALING MODEL
Authors: Kronenberg D. , Everding J. , Wendler L. , Brand M. , Timmen M. , Stange R.
Published: July 2023

Integrin α2β1 is one of the major transmembrane receptors for fibrillary collagen. In native bone we could show that the absence of this protein led to a protective effect against age-related osteoporosis. The objective of this study was to elucidate the effects of integrin α2β1 deficiency on fracture repair and its underlying mechanisms.

Standardised femoral fractures were stabilised by an intramedullary nail in 12 week old female C57Bl/6J mice (wild type and integrin α2-/-). After 7, 14 and 28 days mice were sacrificed. Dissected femura were subjected to µCT and histological analyses. To evaluate the biomechanical properties, 28-day-healed femura were tested in a torsional testing device. Masson goldner staining, Alizarin blue, IHC and IF staining were performed on paraffin slices. Blood serum of the animals were measured by ELISA for BMP-2. Primary osteoblasts were analysed by in/on-cell western technology and qRT-PCR.

Integrin α2β1 deficient animals showed earlier transition from cartilaginous callus to mineralized callus during fracture repair. The shift from chondrocytes over hypertrophic chondrocytes to bone-forming osteoblasts was accelerated. Collagen production was increased in mutant fracture callus. Serum levels of BMP-2 were increased in healing KO mice. Isolated integrin deficient osteoblast presented an earlier expression and production of active BMP-2 during the differentiation, which led to earlier mineralisation. Biomechanical testing showed no differences between wild-type and mutant bones.

Knockout of integrin α2β1 leads to a beneficial outcome for fracture repair. Callus maturation is accelerated, leading to faster recovery, accompanied by an increased generation of extra-cellular matrix material. Biomechanical properties are not diminished by this accelerated healing. The underlying mechanism is driven by an earlier availability of BMP-2, one main effectors for bone development. Local inhibition of integrin α2β1 is therefore a promising target to accelerate fracture repair, especially in patients with retarded healing.
SURGICAL TEAMS WHO TRAIN TOGETHER IN VIRTUAL REALITY OUTPERFORM THOSE WHO TRAIN INDIVIDUALLY: A RANDOMIZED CONTROLLED TRIAL FOR LEARNING ANTERIOR APPROACH TOTAL HIP ARTHROPLASTY
Authors: Edwards T. , Gupta S. , Soussi D. , Patel A. , Khan S. , Liddle A. , Cobb J. , Logishetty K.
Published: July 2023

Current evidence suggests that superior surgical team performance is linked to fewer intra-operative errors, reductions in mortality and even improved patient outcomes. Virtual reality has demonstrated excellent efficacy in training surgeons and scrub nurses individually, however its impact on training teams is currently unknown. This study aimed to assess if training together (scrub nurse and surgeon) in an innovative multiplayer virtual reality program was superior to single player training for novices learning anterior approach total hip arthroplasty (AA-THA).

40 participants (20 novice surgeons (CT1-ST3 level) and 20 novice scrub nurses) were enrolled in this study and randomised to individual or team virtual reality training. Individually-trained participants played with virtual avatar counterparts, whilst teams trained live in pairs (surgeon and scrub nurse). Both groups underwent 5 VR training sessions over 6 weeks. Subsequently, they underwent a real-life assessment in which they performed AA-THA on a high-fidelity model with real equipment in a simulated operating theatre. Teams performed together and individually-trained participants were randomly paired up with a solo player of the opposite role. Videos of the assessment were marked by two blinded expert assessors. The primary outcome was team performance as graded by the validated NOTECHs II score. Secondary outcomes were procedure time and number of technical errors from an expert pre-defined protocol.

Teams outperformed individually-trained participants for non-technical skills in the real-world assessment (NOTECHS-II score 50.3 ± 6.04 vs 43.90 ± 5.90, p=0.0275). They completed the assessment 28.1% faster (31.22 minutes ±2.02 vs 43.43 ±2.71, p=0.01), and made close to half the number of technical errors when compared to the individual group (12.9 ± 8.3 vs 25.6 ± 6.1, p=0.001).

Multiplayer, team training appears to lead to faster surgery with fewer technical errors and the development of superior non-technical skills.