Recently, there is ongoing evidence regarding rapid recovery after orthopaedic surgery, with advantages for the patient relative to post operative pain, complications and functional recovery. The aim of this study is to present our experience in rapid recovery for adolescent idiopathic scoliosis in the last 2 years.

Retrospective study of 36 patients with adolescent idiopathic scoliosis, (age range 11 to 18 years) treated with spinal thoraco-lumbar posterior fusion with rapid post-operative recovery, compared with a similar group, treated with traditional protocol.

We found a statistically significant difference in terms of length-of-stay, patient-controlled-analgesia and use of oppioid and post operative blood transfusions. There was no difference in post operative infection rate.

Our experience shows better functional recovery, satisfactory controlled analgesia and reduction in costs of hospitalization with the use of ERAS protocols.

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

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

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

Introduction. Immunomodulation represents a novel strategy to improve bone healing in combination with low doses of bone morphogenetic growth factors like BMP-2. This study aims to investigate the effect and timing of monoclonal anti-IL-1ß antibody administration with 1μg BMP-2 on bone healing over 14 weeks in a rat femur segmental defect model. Method. 2 mm femoral defects were created in 22-27 weeks-old female Fischer F344 rats, internally fixed with a plate (animal license: GR/19/2022) using established protocols for analgesia and anesthesia. Animals (n=4/group) received either a collagen sponge, a collagen sponge+1μg BMP-2 (InductOs, Medtronic) or a collagen sponge+1μg BMP-2 with a monoclonal anti-IL-1ß antibody (BioXCell, 10 mg/ml), administered intravenously under anesthesia every third day until day 15, from day 0 or 3. In vivo micro-CT was performed after surgery and at 2, 3, 4, 6, 8, 10 and 14-weeks post-OP. Mechanical properties of the operated femurs were assessed by 4-point bending (Instron5866) and compared to contralateral femurs (one-way ANOVA, GraphPad Prism8). Histopathological analysis was performed semi-quantitatively on Giemsa-Eosin-stained sections (Olympus BX63) using a six-grade severity grading scale. Result. Operated femurs with BMP-2 reached an average stiffness of 91±37% of contralateral femurs, femurs in IL-1ß groups 105±11% (day 0) and 111±12% (day 3). Administration of anti-IL-1ß+1μg BMP-2 led to faster cortical bridging (3/4 femurs bridged by week 4 for day 0, 4/4 for day 3) than 1μg BMP-2 alone (0/4 by week 4). Micro-CT results confirmed histopathological evaluation, as collagen sponge alone led to non-union, complete bicortical bridging was observed for 3/4 femurs in the BMP-2 group and for 4/4 femurs in the IL-1β groups after 14 weeks. Conclusion. Anti-IL-1ß had a beneficial effect on late fracture healing with faster cortical bridging and new bone formation than 1μg BMP-2 alone. Acknowledgments. AO foundation. We thank Andrea Furter, Alisa Hangartner and Thomas Krüger for technical support

Abstract. Objectives. The objective of this study is to investigate if genomic sequencing is a useful method to diagnose orthopaedic infections. Current methods used to identify the species of bacteria causing orthopaedic infections take considerable time and the results are frequently insufficient for guiding antibiotic treatment. The aim here is to investigate if genomic sequencing is a faster and more reliable method to identify the species of bacteria causing infections. Current methods include a combination of biochemical markers and microbiological cultures which frequently produce false positive results and false negative results. Methods. Samples of prosthetic fluid were obtained from surgical interventions to treat orthopaedic infections. DNA is extracted from these samples lab and nanopore genomic sequencing is performed. Initial investigations informed that a sequencing time of 15 minutes was sufficient. The resulting genomic sequence data was classified using Basic Local Alignment Tool (BLAST) against the NCBI bacterial database and filtered by only including reads with an identity score of 90 and E-value of 1e-50. An E-value of 1e-50 suggests a high-quality result and is commonly used when analysing genomic data. This data was then filtered in R Studio to identify if any species were associated with orthopaedic infections. The results from genomic sequencing were compared to microbiology results from the hospital to see if the same species had been identified. The whole process from DNA extraction to output took approximately 2 hours, which was faster than parallel microbiological cultures. Results. In these preliminary analyses, 15 samples have been collected from patients with confirmed/suspected orthopaedic infections. To date, 11 samples from confirmed infected patients have been sequenced and a summary of the findings are presented in the table attached. As well as finding bacteria species to match microbiological cultures, genomic sequencing has also identified bacteria when culture results have been negative, but the patient is known to have an infection due to clinical indication and previous culture results. This example suggests genomic sequencing may have higher sensitivity than microbiological cultures at detecting bacteria causing orthopaedic infections. Results in table indicate the identification of bacteria from genomic sequencing that match microbiological cultures are high quality. Conclusions. Preliminary data presented using genomic sequencing suggests that the technique may be useful to identify bacterial species causing orthopaedic infections and can do so in a shorter time frame than current microbial methods. The results from genomic sequencing all produced a number of false positive results which hopefully can be reduced by improving the bioinformatic techniques used and increasing the sample number to include individuals without an infection. Further analysis will also look at identifying antibiotic resistance genes in the sequencing data and seeing if this ca be used to predict which patients will and will not respond to antibiotic treatment. The aim at the end of this project is to demonstrate if genomic sequencing is a more sensitive method to identify bacteria causing orthopaedic infections that current methods and if it can be used to guide antibiotic treatment. Include limitations, next steps and bigger picture. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

The HIPGEN study funded under EU Horizon 2020 (Grant 7792939) has the aim to investigate the potential of the first regenerative cell therapy for the improvement of recovery after muscle injury in hip fracture patients. For this aim we intramuscularly injected placental derived mesenchymal stromal cells during hip fracture arthroplasty. Despite not having reached the primary endpoint, which was the Short Physical Performance Battery, we could observe an increase in abductor muscle strength and a faster return to balance looking at symmetry in insole measurements during follow up

Mesenchymal stem cells (MSC) have been used for bone regenerative applications as an alternative approach to bone grafting. Selecting the appropriate source of MSC is vital for the success of this therapeutic approach. MSC can be obtained from various tissues, but the most used sources of MSC are Bone marrow (BMSC), followed by adipose tissue (ASC). A donor-matched comparison of these two sources of MSC ensures robust and reliable results. Despite the similarities in morphology and immunophenotype of donor-matched ASC and BMSC, differences existed in their proliferation and in vitro differentiation potential, particularly osteogenic differentiation that was superior for BMSC, compared to ASC. However, these differences were substantially influenced by donor variations. In vivo, although the upregulated expression of osteogenesis-related genes in both ASC and BMSC, more bone was regenerated in the calvarial defects treated with BMSC compared to ASC, especially during the initial period of healing. According to these findings, compared to ASC, BMSC may result in faster regeneration and healing, when used for bone regenerative applications

Abstract. Objectives. Non-technical skills including teamwork play a pivotal role in surgical outcomes. Virtual reality is effective at improving technical skills, however there is a paucity of evidence on team-based virtual reality (VR) training. This study aimed to assess if multiplayer virtual reality training was superior to solo training for acquisition of both technical and non-technical skills in learning the complex anterior approach total hip arthroplasty operation. Methods. 10 novice surgeons and 10 novice scrub nurses, were randomised to solo or team virtual reality training to perform anterior approach total hip arthroplasty. Solo participants trained with virtual avatar counterparts, whilst teams trained in pairs (surgeon and scrub nurse). Both groups underwent 5 VR training sessions over 6 weeks. Then, 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 solo participants were randomly paired up with a solo player of the opposite role. Videos of the assessment were marked by two blinded expert assessors. Outcomes were procedure time, procedural errors from an expert pre-defined protocol and acetabular component positioning. Non-technical skills were assessed using the NOTECHs II and NOTSS scores. Results. Teams were 28.11% faster than solos in the real world assessment (31.22 minutes ±2.02 vs 43.43 ±2.71, p=0.01), with 34.91% less errors (−15.25 errors ±3.09 vs −23.43 ±1.84, p=0.04). Teams had significantly higher NOTSS and NOTECHS II scores when compared to solos (p<0.001). 8/10 surgeons placed the acetabular component within the target safe zone. Conclusions. Multiplayer training appears to lead to faster surgery with fewer technical errors and the development of superior non-technical skills. VR learnt skills appear to translate to the physical world. This supports the application of multidisciplinary learning to create a more integrated approach to surgical team training

Abstract. Objectives. Evidence supporting the use of immersive virtual reality (iVR) training in orthopaedic procedures is rapidly growing. However, the impact of the timing of delivery of this training is yet to be tested. This study investigated whether spaced iVR training is more effective than massed iVR training for novices learning hip arthroplasty. Methods. 24 medical students with no hip arthroplasty experience were randomised to learning total hip arthroplasty using the same iVR simulation training either once-weekly or once-daily for four sessions. Participants underwent a baseline physical world assessment to orientate an acetabular component on a saw bone pelvis, and a baseline knowledge test. In iVR, we recorded procedural errors, time, numbers of prompts required and path lengths of the hands and head across 4 sessions. To assess skill retention, the iVR and baseline physical world assessments were repeated at one-week and one-month. Results. Baseline characteristics between the groups were comparable (p > 0.05). The daily group demonstrated faster skills acquisition, reducing the mean number of procedural errors from 76.8±37.5 (S1) to 11.1±10.1 (S4), compared to the weekly group improvement from 71.1±19.1 (S1) to 17.2±10.6 (S4), p < 0.001. The weekly group error count plateaued remaining at 16±6.7 at 1-week and 17.5±8.5 at one-month, the daily group however, showed poor retention with error counts rising to 17.8±10.5 at 1 week and becoming higher than the weekly group at one-month to (23.2±13.0 vs 17.5±10.5). A similar effect was noted for procedural time and the number of assistive prompts. In the real-world assessment, both groups significantly improved the accuracy of their acetabular component positioning, these improvements were equally maintained. Conclusions. Daily iVR training facilitates faster skills acquisition, however weekly practice has superior skills retention. Skills learnt using both regimes demonstrate sustained transfer to the real-world

MicroRNA (miR) delivery to regulate chronic inflammation hold extraordinary promise, with new therapeutic possibilities emanating from their ability to fine-tune multiple target gene regulation pathways which is an important factor in controlling aberrant inflammatory reactions in complex multifactorial disease. However, several hurdles have prevented advancements in miR-based therapies. These include off-target effects of miRs, limited trafficking, and inefficient delivery. We propose a magnetically guided nanocarrier to transport therapeutically relevant miRs to assist self- resolving inflammation processes at injury sites and reduce the impact of chronic inflammation- related diseases such as tendinopathies. The high prevalence, significant socio-economic burden and increasing recognition of dysregulated immune mediated pathways in tendon disease provide a compelling rationale for exploring inflammation-targeting strategies as novel treatments in this condition. By combining cationic polymers, miR species (e.g., miR 29a, miR155 antagonist), and magnetic nanoparticles in the form of magnetoplexes with highly efficient magnetofection procedures, we developed inexpensive, easy-to-fabricate, and biocompatible systems with competent miR-binding and fast cellular uptake into different types of human cells, namely macrophages and tendon-derived cells. The system was shown to be cell-compatible and to successfully modulate the expression and production of inflammatory markers in tendon cells, with evidence of functional pro-healing changes in immune cell phenotypes. Hence, magnetoplexes represent a simple, safe, and non-viral nanoplatform that enables contactless miR delivery and high- precision control to reprogram cell profiles toward improved pro-regenerative environments. Acknowledgements: ERC CoG MagTendon No.772817; FCT Doctoral Grant SFRD/BD/144816/2019, and TERM. RES Hub (Norte-01-0145-FEDER-022190)

Secondary bone healing is impacted by the extent of interfragmentary motion at the fracture site. It provides mechanical stimulus that is required for the formation of fracture callus. In clinical settings, interfragmentary motion is induced by physiological loading of the broken bone – for example, by weight-bearing. However, there is no consensus about when mechanical stimuli should be applied to achieve fast and robust healing response. Therefore, this study aims to identify the effect of the immediate and delayed application of mechanical stimuli on secondary bone healing. A partial tibial osteotomy was created in twelve Swiss White Alpine sheep and stabilized using an active external fixator that induced well-controlled interfragmentary motion in form of a strain gradient. Animals were randomly assigned into two groups which mimicked early (immediate group) and late (delayed group) weight-bearing. The immediate group received daily stimulation (1000 cycles/day) from the first day post-op and the delayed group from the 22nd day post-op. Healing progression was evaluated by measurements of the stiffness of the repair tissue during mechanical stimulation and by quantifying callus area on weekly radiographs. At the end of the five weeks period, callus volume was measured on the post-mortem high-resolution computer tomography (HRCT) scan. Stiffness of the repair tissue (p<0.05) and callus progression (p<0.01) on weekly radiographs were significantly larger for the immediate group compared to the delayed group. The callus volume measured on the HRCT was nearly 3.2 times larger for the immediate group than for the delayed group (p<0.01). This study demonstrates that the absence of immediate mechanical stimuli delays callus formation, and that mechanical stimulation already applied in the early post-op phase promotes bone healing

The application of immune regenerative strategies to deal with unsolved pathologies, such as tendinopathies, is getting attention in the field of tissue engineering exploiting the innate immunomodulatory potential of stem cells [1]. In this context, Amniotic Epithelial Cells (AECs) represent an innovative immune regenerative strategy due to their teno-inductive and immunomodulatory properties [2], and because of their high paracrine activity, become a potential stem cell source for a cell-free treatment to overcome the limitations of traditional cell-based therapies. Nevertheless, these immunomodulatory mechanisms on AECs are still not fully known to date. In these studies, we explored standardized protocols [3] to better comprehend the different phenotypic behavior between epithelial AECs (eAECs) and mesenchymal AECs (mAECs), and to further produce an enhanced immunomodulatory AECs-derived secretome by exposing cells to different stimuli. Hence, in order to fulfill these aims, eAECs and mAECs at third passage were silenced for CIITA and Nrf2, respectively, to understand the role of these molecules in an inflammatory response. Furthermore, AECs at first passage were seeded under normal or GO-coated coverslips to study the effect of GO on AECs, and further exposed to LPS and/or IL17 priming to increase the anti-inflammatory paracrine activity. The obtained results demonstrated how CIITA and Nrf2 control the immune response of eAECs and mAECs, respectively, under standard or immune-activated conditions (LPS priming). Additionally, GO exposition led to a faster activation of the Epithelial-Mesenchymal transition (EMT) through the TGFβ/SMAD signaling pathway with a change in the anti-inflammatory properties. Finally, the combinatory inflammatory stimuli of LPS+IL17 enhanced the paracrine activity and immunomodulatory properties of AECs. Therefore, AECs-derived secretome has emerged as a potential treatment option for inflammatory disorders such as tendinopathies. Acknowledgement: This research is part of the P4FIT project ESR1, funded under the H2020-ITN-EJD-Marie-Skłodowska-Curie grant agreement 955685

High tibial osteotomy (HTO) is a joint preserving alternative to knee replacement for medial tibiofemoral osteoarthritis in younger, more active patients. The procedure is technically challenging and limited also by ‘one size fits all’ plates which can result in patient discomfort necessitating plate removal. This clinical trial evaluated A novel custom-made HTO system – TOKA (3D Metal Printing LTD, Bath, UK) for accuracy of osteotomy correction and improvements in clinical outcome scores. The investigation was a single-arm single-centre prospective clinical trial (IRCCS Istituto Ortopedico Rizzoli; ClinicalTrials.gov NCT04574570), with recruitment of 25 patients (19M/6F; average age: 54.4 years; average BMI: 26.8), all of whom received the TOKA HTO 3D planning and surgery. All patients were predominantly diagnosed with isolated medial knee osteoarthritis and with a varus deformity under 20°. Patients were CT scanned pre- and post-operatively for 3D virtual planning and correctional assessment. All surgeries were performed by the lead clinical investigator – a consultant knee surgeon with a specialist interest in and clinical experience of HTO. On average, Knee Society Scores (KSS) improved significantly (p<0.001) by 27.6, 31.2 and 37.2 percentage points respectively by 3-, 6- and 12-months post-surgery respectively. Other measures assessed during the study (KOOS, EQ5D) produced similar increases. Our early experience using custom implants is extremely promising. We believe the reduced profile of the plate, as well as the reduced invasiveness and ease of surgery contributed to faster patient recovery, and improved outcome scores compared to conventional techniques. These clinical outcome results compare very favourably other case-series with published KOOS scores using different devices

Primary implant stability is critical for osseointegration and subsequent implant success. Small displacements on the screw/bone interface are necessary for implant success, however, larger displacements can propagate cracks and break anchorage points which causes the screw to fail. Limited information is available on the progressive degradation of stability of an implanted bone screw since most published research is based on monotonic, quasi-static loading [1]. This study aims to address this gap in knowledge. A total of 100 implanted trabecular screws were tested using multi-axial loading test set-up. Screws were loaded in cycles with the applied force increasing 1N in each load cycle. In every load cycle, Peak forces, displacements, and stiffness degradation (calculated in the unloading half of the cycle) where recorded. 10 different loading configurations where tested. The damage vs displacement shows a total displacement at the point of failure between 0.3 and 0.4 mm while an initial stiffness reduction close to 40%. It is also shown that at a displacement of ~0.1 mm, the initial stiffness of every sample had degraded by 20% (or more) meaning that half of the allowable degradation occurred in the first 25-30% of the total displacement. Other studies on screw overloading [1] suggests similar results to our concerning initial stiffness degradation at the end of the loading cycle. Our results also show that the initial stiffness degrades faster with relatively small deformations suggesting that the failure point of an implanted screw might occur before the common failure definition (pull-out force, for example). These results are of great significance since primary implant stability is better explained by the stiffness of the construct than by its failure point

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

In 2021 the bone grafting market was worth €2.72 billion globally. As allograft bone has a limited supply and risk of disease transmission, the demand for synthetic grafting substitutes (BGS) continues to grow while allograft bone grafts steadily decrease. Synthetic BGS are low in mechanical strength and bioactivity, inspiring the development of novel grafting materials, a traditionally laborious and expensive process. Here a novel BGS derived from sustainably grown coral was evaluated. Coral-derived scaffolds are a natural calcium carbonate bio-ceramic, which induces osteogenesis in bone marrow mesenchymal stem cells (MSCs), the cells responsible for maintaining bone homeostasis and orchestrating fracture repair. By 3D printing MSCs in coral-laden bioinks we utilise high throughput (HT) fabrication and evaluation of osteogenesis, overcoming the limitations of traditional screening methods. MSC and coral-laden GelXA (CELLINK) bioinks were 3D printed in square bottom 96 well plates using a CELLINK BIO X printer with pneumatic adapter Samples were non-destructively monitored during the culture period, evaluating both the sample and the culture media for metabolism (PrestoBlue), cytotoxicity (lactose dehydrogenase (LDH)) and osteogenic differentiation (alkaline phosphatase (ALP)). Endpoint, destructive assays used included qRT-PCR and SEM imaging. The inclusion of coral in the printed bioink was biocompatable with the MSCs, as reflected by maintained metabolism and low LDH release. The inclusion of coral induced osteogenic differentiation in the MSCs as seen by ALP secretion and increased RUNX2, collagen I and osteocalcin transcription. Sustainably grown coral was successfully incorporated into bioinks, reproducibly 3D printed, non-destructively monitored throughout culture and induced osteogenic differentiation in MSCs. This HT fabrication and monitoring workflow offers a faster, less labour-intensive system for the translation of bone substitute materials to clinic. Acknowledgements: This work was co-funded by Enterprise Ireland and Zoan Biomed through Innovation Partnership IP20221024

Introduction. The Achilles tendon is the thickest and strongest tendon in the human body. Even though the tendon is so strong, it is one of the most frequently injured tendons. Treatment of patients after rupture is planned conservatively and surgically. Conservative treatment is generally applied to elderly patients with sedentary lives. If the treatment is surgical, it can be planned as open surgery or percutaneous surgery. In our study with rabbits, we wrapped a membrane made of plga (polylactic-co-glycolic acid) nanotubes impregnated with type 1 collagen around the tendon in rabbits that underwent open Achilles tendon repair surgery. After surgery, biomechanical and histological tests were performed on the tendons. Method. In the study consisting of 24 rabbits, 2 groups were created by random distribution. In the study group, after the Achilles tendon rupture was created, a type 1 collagen-impregnated plga-based membrane was placed around the tendon after the repair of 1 modified Kesslerr suture. In the control group, after the Achilles tendon rupture was created, 1 modified Kessler suture and Tendon repair was performed with the application of 3 primary sutures. At the end of the 6th week of the study, the rabbits in 2 groups were randomly distributed and histological examination was performed. Additionally, biomechanical testing was performed. Bonar and Movın scoring were used in histological examinations. Result. As a result of biomechanical tests, it was seen that the resistance of the tendon against rupture was higher in the study group than in the control group. In addition, it was observed that the tendon rupture time was longer in the study group than in the control group. Histological examinations gave supportive results from biomechanical tests. Conclusion. We think that the use of collagen-impregnated plga-based nanotubes in the surgical treatment of Achilles tendon ruptures has a positive healing effect. Although we think that the return to normal life after surgery may be faster, we believe that more clinical studies are needed

Introduction. With advances in artificial intelligence, the use of computer-aided detection and diagnosis in clinical imaging is gaining traction. Typically, very large datasets are required to train machine-learning models, potentially limiting use of this technology when only small datasets are available. This study investigated whether pretraining of fracture detection models on large, existing datasets could improve the performance of the model when locating and classifying wrist fractures in a small X-ray image dataset. This concept is termed “transfer learning”. Method. Firstly, three detection models, namely, the faster region-based convolutional neural network (faster R-CNN), you only look once version eight (YOLOv8), and RetinaNet, were pretrained using the large, freely available dataset, common objects in context (COCO) (330000 images). Secondly, these models were pretrained using an open-source wrist X-ray dataset called “Graz Paediatric Wrist Digital X-rays” (GRAZPEDWRI-DX) on a (1) fracture detection dataset (20327 images) and (2) fracture location and classification dataset (14390 images). An orthopaedic surgeon classified the small available dataset of 776 distal radius X-rays (Arbeidsgmeischaft für Osteosynthesefragen Foundation / Orthopaedic Trauma Association; AO/OTA), on which the models were tested. Result. Detection models without pre-training on the large datasets were the least precise when tested on the small distal radius dataset. The model with the best accuracy to detect and classify wrist fractures was the YOLOv8 model pretrained on the GRAZPEDWRI-DX fracture detection dataset (mean average precision at intersection over union of 50=59.7%). This model showed up to 33.6% improved detection precision compared to the same models with no pre-training. Conclusion. Optimisation of machine-learning models can be challenging when only relatively small datasets are available. The findings of this study support the potential of transfer learning from large datasets to improve model performance in smaller datasets. This is encouraging for wider application of machine-learning technology in medical imaging evaluation, including less common orthopaedic pathologies

3D spheroid culture is a bridge between standard 2D cell culture and in vivo research which mimics the physiological microenvironment in scaffold-free conditions. Here, this 3D technique is being investigated as a potential method for engineering bone tissue in vitro. However, spheroid culture can exhibit limitations, such as necrotic core formation due to the restricted access of oxygen and nutrients. It is therefore important to determine if spheroids without a sizeable necrotic core can be produced. This study aims to understand necrotic core formation and cell viability in 3D bone cell spheroids using different seeding densities and media formulations. Differentiated rat osteoblasts (dRObs) were seeded in three different seeding densities (1×10. 4. , 5×10. 4. , 1×10 cells) in 96 well U-bottom cell-repellent plates and in three different media i.e., Growth medium (GM), Mineralisation medium 1 (MM1) and MM2. Spheroids were analysed from day 1 to 28 (N=3, n=2). Cell count and viability was assessed by trypan blue method. One way ANOVA and post-hoc Tukey test was performed to compare cell viability among different media and seeding densities. Histological spheroid sections were stained with hematoxylin and eosin (H&E) to identify any visible necrotic core. Cell number increased from day 1 to 28 in all three seeding densities with a notable decrease in cell viability. 1×10. 4. cells proliferated faster than 5×10. 4. and 1×10. 5. cells and had proportionately similar cell death. The necrotic core area was relatively equivalent between all cell seeding densities. The larger the spheroid size, the larger is the size of the necrotic core. This study has demonstrated that 3D spheroids can be formed from dRobs at a variety of seeding densities with no marked difference in necrotic core formation. Future studies will focus on utilising the bone cell spheroids for engineering scalable scaffold-free bone tissue constructs