Aims. The aim of this study was to evaluate the radiological outcome of patients with large bone defects in the femur and tibia who were treated according to the guidelines of the diamond concept in our department (Centre for Orthopedics, Trauma Surgery, and Paraplegiology). Methods. The following retrospective, descriptive analysis consists of patients treated in our department between January 2010 and December 2021. In total, 628 patients were registered, of whom 108 presented with a large-sized defect (≥ 5 cm). A total of 70 patients met the inclusion criteria. The primary endpoint was radiological consolidation of nonunions after one and two years via a modified Lane-Sandhu Score, including only radiological parameters. Results. The mean defect size was 6.77 cm (SD 1.86), with the largest defect being 12.6 cm. Within two years after surgical treatment, 45 patients (64.3%) presented consolidation of the previous nonunion. After one year, six patients (8.6%) showed complete consolidation and 23 patients (32.9%) showed a considerable callus formation, whereas 41 patients (58.6%) showed a Lane-Sandhu score of 2 or below. Two years after surgery, 24 patients (34.3%) were categorized as Lane-Sandhu score 4, another 23 patients (32.9%) reached a score of 3, while 14 patients (20.0%) remained without final consolidation (score ≤ 2). A total of nine patients (12.9%) missed the two-year follow-up. The mean follow-up was 44.40 months (SD 32.00). The mean time period from nonunion surgery to consolidation was 16.42 months (SD 9.73). Conclusion. Patients with presentation of a large-sized nonunion require a structured and sufficiently long follow-up to secure the consolidation of the former nonunion. Furthermore, a follow-up of at least two years is required in order to declare a nonunion as consolidated, given that a significant part of the nonunions declared as not consolidated at one year showed consolidation within the second year. Moreover, the proven “gold standard” of a two-step procedure, so called Masquelet technique, shows effectiveness. Cite this article: Bone Jt Open 2024;6(1):26–34

Aims

Tibial fixation in revision total knee arthroplasty (rTKA) can present surgical challenges. It has been suggested that appropriate fixation in at least two of the three anatomical zones (epiphysis, metaphysis, and diaphysis) is essential for implant survival. However, supporting clinical data are lacking. In this retrospective case-control study, we investigated the relationship between zonal fixation of hybrid rTKA tibial components and re-revision total knee arthroplasty for aseptic loosening (rrTKA-AL).

Aims

The “2 to 10% strain rule” for fracture healing has been widely interpreted to mean that interfragmentary strain greater than 10% predisposes a fracture to nonunion. This interpretation focuses on the gap-closing strain (axial micromotion divided by gap size), ignoring the region around the gap where osteogenesis typically initiates. The aim of this study was to measure gap-closing and 3D interfragmentary strains in plated ovine osteotomies and associate local strain conditions with callus mineralization.

Cite this article: Bone Joint Res 2024;13(12):790–792.

Addressing bone defects is a complex medical challenge that involves dealing with various skeletal conditions, including fractures, osteoporosis (OP), bone tumours, and bone infection defects. Despite the availability of multiple conventional treatments for these skeletal conditions, numerous limitations and unresolved issues persist. As a solution, advancements in biomedical materials have recently resulted in novel therapeutic concepts. As an emerging biomaterial for bone defect treatment, graphene oxide (GO) in particular has gained substantial attention from researchers due to its potential applications and prospects. In other words, GO scaffolds have demonstrated remarkable potential for bone defect treatment. Furthermore, GO-loaded biomaterials can promote osteoblast adhesion, proliferation, and differentiation while stimulating bone matrix deposition and formation. Given their favourable biocompatibility and osteoinductive capabilities, these materials offer a novel therapeutic avenue for bone tissue regeneration and repair. This comprehensive review systematically outlines GO scaffolds’ diverse roles and potential applications in bone defect treatment. Cite this article: Bone Joint Res 2024;13(12):725–740

The December 2024 Trauma Roundup. 360. looks at: Percutaneous lumbopelvic fixation is effective in the management of unstable transverse sacral fractures; A systematic review on autologous matrix-induced chondrogenesis (AMIC) for chondral knee defects; Stable clinical and radiological outcomes at medium and over five-year follow-up of calcaneus fracture open reduction internal fixation using a sinus tarsi approach; Right or left? It might make a difference; Suprapatellar versus infrapatellar tibial nailing – is there a difference in anterior knee pain and function?; Can patients safely weightbear following ankle fracture fixation?; Anterior-to-posterior or a plate fixation for posterior malleous fractures?; Audio distraction for traction pin insertion: a prospective randomized controlled study; Is intramedullary nailing of femoral diaphyseal fractures in the lateral decubitus position as safe and effective as on a traction table?

The December 2024 Foot & Ankle Roundup³⁶⁰ looks at: Tibiotalar sector and lateral ankle instability; Isolated subtalar fusion and correction of progressive collapsing foot deformity; Diabetic control and postoperative complications following ankle fracture fixation; Are insoles of any benefit for plantar fasciitis?; Postoperative foot shape and patient-reported outcome following surgery for progressing collapsing foot deformity; Calcaneo-stop procedure for symptomatic flexible flatfoot in children.

Aims. Calcaneal osteomyelitis remains a difficult condition to treat with high rates of recurrence and below-knee amputation, particularly in the presence of severe soft-tissue destruction. This study assesses the outcomes of single-stage orthoplastic surgical treatment of calcaneal osteomyelitis with large soft-tissue defects. Methods. A retrospective review was performed of all patients who underwent combined single-stage orthoplastic treatment of calcaneal osteomyelitis (01/2008 to 12/2022). Primary outcome measures were osteomyelitis recurrence and below-knee amputation (BKA). Secondary outcome measures included flap failure, operating time, complications, and length of stay. Results. A total of 30 patients (14 female, 16 male; mean age 53.7 years (95% CI 48.0 to 59.5)) underwent combined orthoplastic surgical treatment for BACH “complex” calcaneal osteomyelitis with a median follow-up of 31 months (IQR 11.75 to 49.25). Of these, 19 received a local flap and 11 received a free flap. The most common causes were fracture-related infection (n = 12; 40%) and ulceration (n = 10; 33%); 21 patients (70%) had already undergone at least one operation elsewhere. Osteomyelitis was eradicated in 23 patients (77%). There were seven patients who developed recurrent osteomyelitis (23%), all in the local flap group. One patient required a BKA. Univariate analysis revealed that local flap reconstruction (OR 13.5 (95% CI 0.7 to 269.7); p = 0.029) and peripheral vascular disease (OR 16.5 (95% CI 1.35 to 203.1); p = 0.008) were associated with increased risk of recurrence. Free flap reconstruction took significantly longer intraoperatively than local flaps (mean 481 minutes (408 to 554) vs mean 168 minutes (119 to 216); p < 0.001), but without significant differences in length of stay or frequency of outpatient appointments. Conclusion. In our study involving 30 patients, single-stage orthoplastic management was associated with 77% (n = 23) eradication of infection and only one amputation in this complex and comorbid patient group. Risk factors for failure were peripheral vascular disease and local flap reconstruction. While good outcomes can be achieved, this treatment requires high levels of inpatient and outpatient care. Cite this article: Bone Joint J 2024;106-B(12):1443–1450

Introduction. Since the expanded war in Ukraine in 2022, explosives, mines, debris, blast waves, and other factors have predominantly caused injuries during artillery or rocket attacks. These injuries, such as those from shelling shrapnel, involve high-energy penetrating agents, resulting in extensive necrosis and notable characteristics like soft tissue defects and multiple fragmentary fractures with bone tissue defects and a high rate of infection complications caused by multi resistant gram-negative (MRGN) pathogens. Material and Methods. We conducted a prospective study at our center between March 2022 and December 2023. Out of the 56 patients from Ukraine, 21 met the inclusion criteria who had severe war injuries were included in the study. Each of these patients presented with multiple injuries to both bones and soft tissues, having initially undergone treatment in Ukraine involving multiple surgeries. The diagnosis of infection was established based on the EBJIS criteria. Prior to our treatment patients had undergone multiple revision surgeries, including debridement, biopsies, implant and fixator replacement. Additionally, soft tissue management required previously VAC therapy and flap reconstruction for successful treatment. Results. All 21 infections manifested as bone infections (11; 52%), followed by implant-associated infections (5; 24%), soft tissue infections (4; 19%), and septic arthritis (1; 5%). In all patients, the infection was polymicrobial, caused by 3- and 4-MRGN pathogens, as Klebsiella pneumonia 4MRGN, Proteus mirabilis 4MRGN, Enterobacter cloacae 4MRGN etc. Upon admission, all patients carried a diagnosis and exhibited signs indicative of chronic infection. 19 (90.5%) patients required complex antibiotic regimens combined with multiple wound revisions and debridements, changes of fixators and combination of systemic and local antibiotic therapy. In 6 patients (28%) high dosages of local antibiotics such as gentamycin, vancomycin and meropenem were incorporated into a carrier of bio-absorbable calcium sulfate, calcium sulfate/hydroxyapatite which were introduced into the hip joint, femoral canal or bone defect for dead space management during the surgery. When local antibiotics were administered at intervals, the microbiology results at implantation showed negative results. 2 (9%) patients had new infections (different site, different pathogens), 1 (4.8%) is still under the treatment. In 17 (81%) patients infection complications were treated successfully with no recurrence of infection. Conclusion. War injuries result in complex bone and soft-tissue infections caused by 3-, 4-MRGN pathogens. Addressing this challenge necessitates multidisciplinary approach with multiple, thorough surgical debridements, effective local, and systemic antimicrobial therapy. As for the outlook we can see potential in local antibiotic carriers

Aim. Decubitus ulcers are found in approximately 4.7% of hospitalized patients, with a higher prevalence (up to 30%) among those with spinal cord injuries. These ulcers are often associated with hip septic arthritis and/or osteomyelitis involving the femur. Girdlestone resection arthroplasty is a surgical technique used to remove affected proximal femur and acetabular tissues, resulting in a substantial defect. The vastus lateralis flap has been employed as an effective option for managing this dead space. The aim of this study was to evaluate the long-term outcomes of this procedure in a consecutive series of patients. Method. A retrospective single-center study was conducted from October 2012 to December 2022, involving 7 patients with spinal cord injuries affected by chronic severe septic hip arthritis and/or femoral head septic necrosis as a consequence of decubitus ulcers over trochanter area. All patients underwent treatment using a multidisciplinary approach by the same surgical team (orthopedic and plastic surgeons) along with infectious disease specialists. The treatment consisted of a one-stage procedure combining Girdlestone resection arthroplasty with unilateral vastus lateralis flap reconstruction, alongside targeted antibiotic therapy. Complications and postoperative outcomes were assessed and recorded. The mean follow-up period was 8 years (range 2-12). Results. Of the 7 patients, 5 were male and 2 were female, with a mean age of 50.3 years at the time of surgery. Minor wound dehiscence occurred in 28.6% of the flap sites, and 2 patients required additional revisional procedures—one for hematoma and the other for bleeding. There were no instances of flap failure, and complete wound healing was achieved in an average of 32 days (range 20-41), with the ability to load over the hip area. No cases of infection recurrence or relapse were observed. Conclusions. An aggressive surgical approach is strongly recommended for managing chronic hip septic arthritis or proximal femur osteomyelitis in patients with spinal cord injuries. A single-stage procedure combining Girdlestone resection arthroplasty with immediate vastus lateralis muscle flap reconstruction proves to be an effective strategy for dead space management and localized antibiotic delivery through the vastus muscle, giving reliable soft tissue coverage around the proximal femur to avoid the recurrence of pressure ulcers. The implementation of a standardized multidisciplinary protocol contributes significantly to the success of reconstruction efforts

Aim. Bone infections often manifest with soft tissue complications such as severe scarring, fistulas, or ulcerations. Ideally, their management involves thorough debridement of infected bone and associated soft tissues, along with achieving stable bone structure, substantial tissue coverage, and long-term antibiotic therapy. The formation of a multidisciplinary team comprising orthopedic surgeons, plastic surgeons, and infectious disease specialists is essential in addressing the most complex cases. Method. We conducted a retrospective study during six years (2018-2023) at our university center. Focusing on the most challenging cases, we included patients with bone infections in the leg and/or foot requiring free flap reconstruction. Each patient underwent simultaneous bone debridement and reconstruction by the orthopedic team, alongside soft tissue debridement and free flap reconstruction by the plastic surgery team. Targeted antibiotic therapy for either 6 weeks (acute) or 12 weeks (chronic osteitis) was initiated based on intraoperative cultures. Additional procedures such as allografts, arthrodesis, or autografts were performed if necessary. We analyzed the rates of bone union, infection resolution, and limb preservation. Results. Forty-five patients were enrolled. Twenty-four patients (53.3%) had urgent indications (e.g., open infected fractures, osteitis, acute osteoarthritis, or wound dehiscence), while 21 (46.7%) underwent elective surgery (e.g., septic pseudarthrosis or chronic osteitis). Two patients underwent amputation due to flap failure (4.4%), and one patient was lost to follow-up. Follow-up of the remaining 42 patients averaged 28 months (range: 6–60 months). During this period, 35 patients (83.4%) experienced no recurrence of infection. Similarly, 35 patients (83.4%) achieved bone union. Overall, the rate of lower limb preservation was 93.3%. Conclusions. Managing bone infection coupled with soft tissue defects brings significant challenges. Although the majority of patients treated here belong to a complex framework based on the BACH classification, the outcomes achieved here appear to align with those of the simpler cases, thanks to optimal care with a dedicated septic ortho-plastic team. Our study demonstrates a notable success rate in treating infection, achieving bone consolidation, and preserving lower limb function

Aim. Aim of this study was to establish the first clinical results after implantation of ultrathin silver-polysiloxane-coated. 1. plates in the treatment of infected non-union of the femoral shaft. Method. As part of the REFECT study, a prospective, non-interventional analysis was conducted encompassing all patients who received internal stabilization with a silver-coated. 1. plate from 01/2023 to 09/2024 as part of the treatment for infected non-union of the femur. Standardized clinical follow-ups including PROMs (WOMAC-Index, LEF-S, EQ-5D, VAS) and X-rays were performed 3, 6, 12 (and 24) months postoperatively. For comparison, a retrospective analysis of 76 patients with infected femoral non-union, who had received a stabilization with an uncoated plate in the past 10 years, was performed. Results. The mean follow-up of the 8 included patients (mean bone defect: 3.6 cm) was 9 months (as of 04/24). Multiresistant bacteria were found in the intraoperative samples of 5 patients. The concentration of silver ions in blood serum reached a maximum of 0.014 mg/l in the laboratory controls. All patients showed a positive healing process with no sign of re-infection and no adverse procedure-associated events. Full weight bearing was achieved after an average of 4 months (n=6) with improved WOMAC-, LEF-S-, EQ-5D and VAS-score at 1-year FU. In the reference group (uncoated, mean FU: 3.5 years), there was a re-infection rate of 25 %, mostly in the first 2 years. Difficult-to-treat bacteria were detected in 22%, multiresistant Staph. epidermidis in 28% of cases. Conclusions. -. The silver-coated. 1. implants showed good biocompatibility with no evidence of procedure-associated complications. -. The use of silver-coated. 1. implants could reduce the risk of re-infection. -. Further clinical data with longer follow-up are needed to assess the long-term value of the procedure

Aims

The Bankart and Latarjet procedures are two of the most common surgical techniques to treat anterior shoulder instability with satisfactory clinical and functional outcomes. However, the outcomes in the adolescent population remain unclear, and there is no information regarding the arthroscopic Latarjet in this population. The purpose of this study was to evaluate the outcomes of the arthroscopic Bankart and arthroscopic Latarjet procedures in the management of anterior shoulder instability in adolescents.

Background. The molecular mechanisms underlying non-union bone fractures largely remain elusive. Recently, spatial transcriptomics approaches for musculoskeletal tissue samples have been developed requiring direct placement of histology sections on barcoded slides. However, Formalin-Fixed-Paraffin-Embedded (FFPE) bone sections have been associated with limited RNA quality and read depth compared to soft tissue. Here, we test spatial transcriptomics workflows based on transcriptomic probe transfer to characterize molecular features discriminating non-union and union bone fractures in mice. Method. Histological sections (n=8) used for spatial transcriptomics (Visium CytAssist FFPE; 10x Genomics, n=4 on glass slides, n=4 on hydrogel-coated slides) were obtained from a fracture healing study in female 20-week-old C57BL/6J mice receiving either a femur osteotomy (0.7mm) or a segmental defect (2.4mm) (license 22/2022, Grisons CH). Sequence alignment and manual segmentation of different tissues (bone, defect region/callus, bone marrow, muscle) were performed using SpaceRanger and LoupeBrowser (10x Genomics). Differential gene expression was performed using DESeq2 (Seurat) followed by Gene-Set-Enrichment-Analysis (GSEA) of Gene Ontology (ClusterProfiler). Group comparison of quality measures was done using a Welch's t-test. Results are given as mean±standard deviation. Result. The quality measures, mean counts, and genes per spot, were significantly ~10× higher for sections on hydrogel slides (counts: 4700±1796, genes: 2389±1170) compared to glass slides (counts: 463±415, genes: 250±223). In challenging tissues like cortical bone, we reached high counts+genes in comparison to published data. Direct comparison of a non-union and union section showed a total of 432 differentially regulated genes, 538 in the defect region/callus. GSEA revealed differential regulation of pathways involved in muscle organ morphogenesis, cartilage development and endochondral ossification. Conclusions. Optimized spatial transcriptomics workflows based on transcriptomic probe transfer enable for improved read depth in musculoskeletal tissue enabling the characterization of molecular features discriminating non-union and union bone fractures. Acknowledgements. AO Foundation (AOTRAUMA), SNSF (PhD salary)

Introduction. Homogenous and consistent preparations of mesenchymal stem cells (MSCs) can be acquired by selecting them for integrin α10β1 (integrin a10-MSCs). Safety and efficacy of intra-articular injection of allogeneic integrin a10-MSCs were shown in two post-traumatic osteoarthritis horse studies. The current study investigated immunomodulatory capacities of human integrin a10-MSCs in vitro and their cell fait after intra-articular injection in rabbits. Method. The concentration of produced immunomodulatory factors was measured after licensing integrin a10-MSCs with pro-inflammatory cytokines. Suppression of T-cell proliferation was determined in co-cultures with carboxyfluorescein N-succinimidyl ester (CFSE) labelled human peripheral blood mononuclear cells (PBMCs) stimulated with anti-CD3/CD28 and measuring the CFSE intensity of CD4+ cells. Macrophage polarization was assessed in co-cultures with differentiated THP-1 cells stimulated with lipopolysaccharide and analysing the M2 macrophage cell surface markers CD163 and CD206. In vivo homing and regeneration were investigated by injecting superparamagnetic iron oxide nanoparticles conjugated with Rhodamine B-labeled human integrin a10-MSCs in rabbits with experimental osteochondral defects. MSC distribution in the joint was followed by MRI and fluorescence microscopy. Result. The production of the immunomodulatory factors indoleamine 2,3-dioxygenase and prostaglandin E2 was increased after inflammatory licensing integrin a10-MSCs. Co-cultures with integrin a10-MSCs suppressed T-cell proliferation and increased the frequency of M2 macrophages. In vivo injected integrin a10-MSCs homed to osteochondral defects and were detected in the repair tissue of the defects up to 10 days after injection, colocalized with aggrecan and type II collagen. Conclusion. This study showed that human integrin a10-MSCs have immunomodulatory capacities and in vivo can home to the site of osteochondral damage and directly participate in cartilage regeneration. This suggests that human integrin α10β1-selected MSCs may be a promising therapy for osteoarthritis with dual mechanisms of action consisting of immunomodulation and homing to damage followed by early engraftment and differentiation into chondrocyte-like cells that deposit hyaline cartilage matrix molecules

Introduction. Cartilage damage is a critical aspect of osteoarthritis progression, but effective imaging strategies remain limited. Consequently, multimodal imaging approaches are receiving increased attention. Gold nanomaterials, renowned for their therapeutic and imaging capabilities, hold promise in drug development. However, their potential for cartilage imaging is rarely discussed. Here, we developed a versatile nanomaterial, AuNC@BSA-Gd-I, for cartilage detection. By leveraging electrostatic interactions with sulfated glycosaminoglycans (sGAG), the AuNC@BSA-Gd-I can effectively penetrate damaged cartilage while accumulating minimally in healthy cartilage. This probe can be visualized or detected using CT, MRI, IVIS, and a gamma counter, providing a comprehensive approach to cartilage imaging. Additionally, we compared the imaging abilities, cartilage visualization capacities, and versatility of currently disclosed multimodal gold nanomaterials with those of AuNC@BSA-Gd-I. Method. The physicochemical properties of nanomaterials were measured. The potential for cartilage visualization of these nanomaterials was assessed using an in vitro porcine model. The sGAG content in cartilage was determined using the dimethylmethylene blue (DMMB) assay to establish the correlation between sGAG concentration and imaging intensity acquired at each modality. Results. The cartilage imaging abilities of AuNC@BSA-Gd-I for CT, MRI, and optical imaging were verified, with each imaging intensity demonstrating a strong correlation with the sGAG content (MRI; R2=0.93, CT; R2=0.83, IVIS; R2=0.79). Furthermore, AuNC@BSA-Gd-. 131. I effectively accumulated in defective cartilage tissue compared to healthy cartilage (23755.38 ± 5993.61 CPM/mg vs. 11699.97 ± 794.93 CPM/mg). Additionally, current gold nanomaterials excelled in individual imaging modalities but lacked effective multimodal imaging ability. Conclusion. Compared to current multimodal gold nanomaterials, AuNC@BSA-Gd-I demonstrates the potential to image cartilage across multiple medical instruments, providing investigators with a more powerful, visible, and convenient approach to detect cartilage defects. Acknowledgements. This work was financially supported by the National Health Research Institute, Taiwan (NHRI-EX112-11029SI), the National Science and Technology Council (NSTC 112-2314-B-182A-105-MY3), and Chang Gung Memorial Hospital, Taiwan (CMRPG8N0781 and CMRPG8M1281-3)

Introduction. Anterior shoulder instability results in labral and osseous glenoid injuries. With a large osseous defect, there is a risk of recurrent dislocation of the joint, and therefore the patient must undergo surgical correction. An MRI evaluation of the patient helps to assess the soft tissue injury. Currently, the volumetric three-dimensional (3D) reconstructed CT image is the standard for measuring glenoid bone loss and the glenoid index. However, it has the disadvantage of exposing the patient to radiation and additional expenses. This study aims to compare the values of the glenoid index using MRI and CT. Method. The present study was a two-year cross-sectional study of patients with shoulder pain, trauma, and dislocation in a tertiary hospital in Karnataka. The sagittal proton density (PD) section of the glenoid and enface 3D reconstructed images of the scapula were used to calculate glenoid bone loss and the glenoid index. The baseline data were analyzed using descriptive statistics, and the Chi-square test was used to test the association of various complications with selected variables of interest. Result. The glenoid index calculated in the current study using 3D volumetric CT images and MR sagittal PD images was 0.95±0.01 and 0.95±0.01, respectively. The CT and MRI glenoid bone loss was 5.41±0.65% and 5.38±0.65%, respectively. When compared, the glenoid index and bone loss calculated by MRI and CT revealed a high correlation and significance with a p-value of <0.001. Conclusions. The study concluded that MRI is a reliable method for glenoid measurement. The sagittal PD sequence combined with an enface glenoid makes it possible to identify osseous defects linked to glenohumeral joint damage and dislocation. The values derived from 3D CT are identical to the glenoid index and bone loss determined using the sagittal PD sequence in MRI

Introduction. The surgical treatment of critical-sized bone defects with complex three-dimensional (3D) geometries is a challenge for the treating surgeon. Additive manufacturing such as 3D printing enables the production of highly individualized bone implants meeting the shape of the patient's bone defect and including a tunable internal structure. In this study, we showcase the design process for patient-specific implants with critical-sized tibia defects. Methods. Two clinical cases of patients with critical tibia defects (size 63×20×21 mm and 50×24×17 mm) were chosen. Brainlab software was used for segmentation of CT data generating 3D models of the defects. The implant construction involves multiple stages. Initially, the outer shell is precisely defined. Subsequently, the specified volume is populated with internal structures using Voronoi, Gyroid, and NaCl crystal structures. Variation in pore size (1.6 mm and 1.0 mm) was accomplished by adjusting scaffold size and material thickness. Results. An algorithmic design process in Rhino and Grasshopper was successfully applied to generate model implants for the tibia from Ct data. By integrating a precise mesh into an outer shell, a scaffold with controlled porosity was designed. In terms of the internal design, both Voronoi and Gyroid form macroscopically homogeneous properties, while NaCl, exhibits irregularities in density and consequently, in the strength of the structure. Data implied that Voronoi and Gyroid structures adapt more precisely to complex and irregular outer shapes of the implants. Conclusion. In proof-of-principle studies customized tibia implants were successfully generated and printed as model implants based on resin. Further studies will include more patient data sets to refine the workflows and digital tools for a broader spectrum of bone defects. The algorithm-based design might offer a tremendous potential in terms of an automated design process for 3D printed implants which is essential for clinical application

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

Introduction. Articular cartilage has a low self-regeneration capacity. Cartilage defects have to be treated to minimize the risk of the onset of osteoarthritis. Bioactive glass (BG) is a promising source for cartilage tissue engineering. Until now, conventional BGs (like BG1393) have been used, mostly for bone regeneration, as they are able to form a hydroxyapatite layer and are therefore, less suited for cartilage reconstruction. The aim of this study is to study the effect of 3D printed hydrogel scaffolds supplemented with spheres of the BG CAR12N to improve the chondrogenesis of mesenchymal stem cells (MSCs). Method. Based on our new glass composition (CAR12N), small BG spheres (25-40 µm) were produced and mixed with hydrogel and primary human (h) MSCs. Grid printed scaffolds were cultivated up to 21 days in expansion or chondrogenic differentiation medium. Macroscopical images of the scaffolds were taken to observe surface changes. Vitality, DNA and sulfated glycosaminoglycan (GAG) content was semiquantitatively measured as well as extracellular matrix gene transcription. Result. It was possible to print grid shaped hydrogel scaffolds with BG spheres and hMSCs. No significant changes in scaffold shape, surface or pore size were detected after 21 days in culture. The BG spheres were homogeneously distributed inside the grids. Vitality was significantly higher in grids with CAR12N spheres in comparison to those without. The DNA content remained constant over three weeks, but was higher in the sphere containing scaffolds than in those without BG spheres. GAG content in the grids increased not only with additional cultivation time but especially in grids with BG spheres in chondrogenic medium. Aggrecan and type II collagen gene expression was significantly higher grids cultured in the chondrogenic differentiation medium. Conclusion. This developed 3D model, is very interesting to study the effect of BG on hMSCs and to understand the influence of leaking ions on chondrogenesis