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.

Aims

The efficacy of saline irrigation for treatment of implant-associated infections is limited in the presence of porous metallic implants. This study evaluated the therapeutic efficacy of antibiotic doped bioceramic (vancomycin/tobramycin-doped polyvinyl alcohol composite (PVA-VAN/TOB-P)) after saline wash in a mouse infection model implanted with titanium cylinders.

Aims

Large bone defects resulting from osteolysis, fractures, osteomyelitis, or metastases pose significant challenges in acetabular reconstruction for total hip arthroplasty. This study aimed to evaluate the survival and radiological outcomes of an acetabular reconstruction technique in patients at high risk of reconstruction failure (i.e. periprosthetic joint infection (PJI), poor bone stock, immunosuppressed patients), referred to as Hip Reconstruction In Situ with Screws and Cement (HiRISC). This involves a polyethylene liner embedded in cement-filled bone defects reinforced with screws and/or plates for enhanced fixation.

Recently, technologies to culture one or more cell types in three dimensions have attracted a great deal of attention in tissue engineering. Particularly, the improved viability, self-renewal capacity, and differentiation potential have been reported for stem cell spheroids. However, it is crucial to modulate spheroid functions with instructive signals to use multi-cellular spheroids in tissue engineering. We have been developing ECM-mimicking fibrous materials decorated with cell-instructive cues, which were incorporated within 3D stem cell spheroids to fine-tune their functions as modular building blocks for bottom-up tissue-engineering applications. In particular, we created composite spheroids of human adipose-derived stem cells (hADSCs) incorporating nanofibers coated with instructive signal of either transforming growth factor-β3 or bone morphogenetic growth factor-2 for chondrogenesis or osteogenesis of stem cells, respectively. The bilayer structure of osteochondral tissue was subsequently mimicked by cultivating each type of spheroid inside 3D-printed construct. The in vitro chondrogenic or osteogenic differentiation of hADSCs within the biphasic construct under general media was locally regulated by each inductive component. More importantly, hADSCs from each spheroid proliferated and sprouted to form the integrated tissue with interface of bone and cartilage tissue. This approach may be applied to engineer complex tissue with hierarchically organized structure

Pseudoarthrosis after spinal fusion is an important complication leading to revision spine surgeries. Iliac Crest Bone Graft is considered the gold standard, but with limited availability and associated co-morbidities, spine surgeons often utilize alternative bone grafts. Determine the non-inferiority of a novel submicron-sized needle-shaped surface biphasic calcium phosphate (BCP<µm) as compared to autograft in instrumented posterolateral spinal fusion. Adult patients indicated for instrumented posterolateral spinal fusion of one to six levels from T10-S2 were enrolled at five participating centers. After instrumentation and preparation of the bone bed, the randomized allocation side of the graft type was disclosed. One side was grafted with 10cc of autograft per level containing a minimum of 50% iliac crest bone. The other side was grafted with 10cc of BCP<µm granules standalone (without autograft or bone marrow aspirate). In total, 71 levels were treated. Prospective follow-up included adverse events, Oswestry Disability Index (ODI), and a fine-cut Computerized Tomography (CT) at one year. Fusion was systematically scored as fused or not fused per level per side by two spine surgeons blinded for the procedure. The first fifty patients enrolled are included in this analysis (mean age: 57 years; 60% female and 40% male). The diagnoses included deformity (56%), structural instability (28%), and instability from decompression (20%). The fusion rate determined by CT for BCP<μm was 76.1%, which compared favorably to the autograft fusion rate of 43.7%. Statistical analysis through binomial modeling showed that the odds of fusion of BCP<μm was 2.54 times higher than that of autograft. 14% of patients experienced a procedure or possible device-related severe adverse event and there were four reoperations. Oswestry Disability Index (ODI) score decreased from a mean of 46.0 (±15.0) to a mean of 31.7 (±16.9), and 52.4% of patients improved with at least 15-point decrease. This data, aiming to determine non-inferiority of standalone BCP<μm as compared to autograft for posterior spinal fusions, is promising. Ongoing studies to increase the power of the statistics with more patients are forthcoming

Biphasic calcium phosphate (BCP) with a characteristic needle-shaped submicron surface topography (MagnetOs) has attracted much attention due to its unique bone-forming ability which is essential for repairing critical-size bone defects such as those found in the posterolateral spine. Previous in vitro and ex-vivo data performed by van Dijk LA and Yuan H demonstrated that these specific surface characteristics drive a favorable response from the innate immune system. This study aimed to evaluate and compare the in vivo performance of three commercially-available synthetic bone grafts, (1) i-FACTOR Putty. ®. , (2) OssDsign. ®. Catalyst Putty and (3) FIBERGRAFT. ®. BG Matrix, with that of a novel synthetic bone graft in a clinically-relevant instrumented sheep posterolateral lumbar spine fusion (PLF) model. The novel synthetic bone graft comprised of BCP granules with a needle-shaped submicron surface topography (MagnetOs) embedded in a highly porous and fibrillar collagen matrix (MagnetOs Flex Matrix). Four synthetic bone grafts were implanted as standalone in an instrumented sheep PLF model for 12 weeks (n=3 bilateral levels per group; levels L2/3 & L4/5), after which spinal fusion was determined by manual palpation, radiograph and µCT imaging (based on the Lenke scale), range-of-motion mechanical testing, and histological and histomorphological evaluation. Radiographic fusion assessment determined bilateral robust bone bridging (Lenke scale A) in 3/3 levels for MagnetOs Flex Matrix compared to 1/3 for all other groups. For µCT, bilateral fusion (Lenke scale A) was found in 2/3 levels for MagnetOs Flex Matrix, compared to 0/3 for i-FACTOR Putty. ®. , 1/3 for OssDsign. ®. Catalyst Putty and 0/3 for FIBERGRAFT. ®. BG Matrix. Fusion assessment for MagnetOs Flex Matrix was further substantiated by histology which revealed significant graft resorption complemented by abundant bone tissue and continuous bony bridging between vertebral transverse processes resulting in bilateral spinal fusion in 3/3 implants. These results show that MagnetOs Flex Matrix achieved better fusion rates compared to three commercially-available synthetic bone grafts when used as a standalone in a clinically-relevant instrumented sheep PLF model

Abstract. Objectives. Neonatal motor development transitions from initially spontaneous to later increasingly complex voluntary movements. A delay in transitioning may indicate cerebral palsy (CP). The general movement optimality score (GMOS) evaluates infant movement variety and is used to diagnose CP, but depends on specialized physiotherapists, is time-consuming, and is subject to inter-observer differences. We hypothesised that an objective means of quantifying movements in young infants using motion tracking data may provide a more consistent early diagnosis of CP and reduce the burden on healthcare systems. This study assessed lower limb kinematic and muscle force variances during neonatal infant kicking movements, and determined that movement variances were associated with GMOS scores, and therefore CP. Methods. Electromagnetic motion tracking data (Polhemus) was collected from neonatal infants performing kicking movements (min 50° knee extension-flexion, <2 seconds) in the supine position over 7 minutes. Tracking data from lower limb anatomical landmarks (midfoot inferior, lateral malleolus, lateral knee epicondyle, ASIS, sacrum) were applied to subject-scaled musculoskeletal models (Gait2354_simbody, OpenSim). Inverse kinematics and static optimisation were applied to estimate lower limb kinematics (knee flexion, hip flexion, hip adduction) and muscle forces (quadriceps femoris, biceps femoris) for isolated kicks. Functional principal component analysis (fPCA) was carried out to reduce kicking kinematic and muscle force waveforms to PC scores capturing ‘modes’ of variance. GMOS scores (lower scores = reduced variety of movement) were collected in parallel with motion capture by a trained operator and specialised physiotherapist. Pearson's correlations were performed to assess if the standard deviation (SD) of kinematic and muscle force waveform PC scores, representing the intra-subject variance of movement or muscle activation, were associated with the GMOS scores. Results. The study compared GMOS scores, kinematics, and muscle force variances from a total of 26 infants with a mean corrected gestational age of 39.7 (±3.34) weeks and GMOS scores between 21 and 40. There was a significant association between the SD of the PC scores for knee flexion and the GMOS scores (PC1: R = 0.59, p = 0.002; PC2: R = 0.49, p = 0.011; PC3: R = 0.56, p = 0.003). The three PCs captured variances of the overall flexion magnitude (66% variance explained), early-to-late kick knee extension (20%), and continual to biphasic kicking (6%). For hip flexion, only the SD of PC1 correlated with GMOS scores (PC1: R = 0.52, p = 0.0068), which captured the variance of the overall flexion magnitude (81%). For the biceps femoris, the SD of PC1 and PC3 associated with GMOS scores (PC1: R = 0.50, p = 0.002; PC3: R = 0.45, p = 0.03), which captured the variance of the overall bicep force magnitude (79%) and early-to-late kick bicep activation (8%). Conclusions. Infants with reduced motor development as scored in the GMOS displayed reduced variances of knee and hip flexion and biceps femoris activation across kicking cycles. These findings suggest that combining objectively measured movement variances with existing classification methods could facilitate the development of more consistent and accurate diagnostic tools for early detection of CP. 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

Aims. Dead-space management, following dead bone resection, is an important element of successful chronic osteomyelitis treatment. This study compared two different biodegradable antibiotic carriers used for dead-space management, and reviewed clinical and radiological outcomes. All cases underwent single-stage surgery and had a minimum one-year follow-up. Methods. A total of 179 patients received preformed calcium sulphate pellets containing 4% tobramycin (Group OT), and 180 patients had an injectable calcium sulphate/nanocrystalline hydroxyapatite ceramic containing gentamicin (Group CG). Outcome measures were infection recurrence, wound leakage, and subsequent fracture involving the treated segment. Bone-void filling was assessed radiologically at a minimum of six months post-surgery. Results. The median follow-up was 4.6 years (interquartile range (IQR) 3.2 to 5.4; range 1.3 to 10.5) in Group OT compared to 4.9 years (IQR 2.1 to 6.0; range 1.0 to 8.3) in Group CG. The groups had similar defect sizes following excision (both mean 10.9 cm. 3. (1 to 30)). Infection recurrence was higher in Group OT (20/179 (11.2%) vs 8/180 (4.4%), p = 0.019) than Group CG, as was early wound leakage (33/179 (18.4%) vs 18/180 (10.0%), p = 0.024) and subsequent fracture (11/179 (6.1%) vs 1.7% (3/180), p = 0.032). Group OT cases had an odds ratio 2.9-times higher of developing any one of these complications, compared to Group CG (95% confidence interval 1.74 to 4.81, p < 0.001). The mean bone-void healing in Group CG was better than in Group OT, in those with ≥ six-month radiological follow-up (73.9% vs 40.0%, p < 0.001). Conclusion. Local antibiotic carrier choice affects outcome in chronic osteomyelitis surgery. A biphasic injectable carrier with a slower dissolution time was associated with better radiological and clinical outcomes compared to a preformed calcium sulphate pellet carrier. Cite this article: Bone Joint Res 2023;12(7):412–422

There is a lack of carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotic for Staphylococcus aureus deep bone infections (DBIs). RIF is also associated with systemic side effects, and known for causing rapid development of antibiotic resistance when given as monotherapy. We evaluated a clinically usedbi-phasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN). It was hypothesized that this combined approach could provide improved biofilm eradication and prevent the development of RIF resistance. Methods: 1) Biofilm eradication: Using a modified crystal violet staining biofilm quantification method, the antibiotics released at different time points (Day 1, 3, 7, 14, 21, 28 and 35) from the hemispherical pellets of CaS/HA(500 mg)-VAN (24.57 mg) / GEN (10.35 mg) composites with or without RIF (8.11 mg) were tested for their ability to disrupt the preformed 48-h old biofilms of S. aureus ATCC 25923, and S. aureus clinical strain P-3 in 96-well microtitre plate. For each tested group of antibiotic fractions, five separate wells were used (n=5). 2) Testing for resistance development: Similar to the method mentioned above the 48-h biofilm embeded bacteria exposed to antibiotic fractions from different time points continuously for 7 days. The biofilms remained were then tested for RIF resistant strains of bacteria. Overall, there was clear antibiofilm biofilm activity observed with CaS/HA-VAN/GEN+RIF combinations compared with CaS/HA-VAN/GEN alone. The S. aureus strains developed resistance to RIF when biofilms were subjected to CaS/HA-RIF alone but not with combinations of CaS/HA-VAN/GEN+RIF. Enhanced antibiofilm effects without development of RIF resistance indicates that biphasic CaS/HA loaded with VAN or GEN could be used as a carrier for RIF for additional local delivery in clinically demanding DBIs. Acknowledgement: We deeply acknowledge the Royal Fysiographic Society of Lund, Landshövding Per Westlings Minnesfond and the Stina and Gunnar Wiberg fond for financial support

Aims. Large acetabular bone defects encountered in revision total hip arthroplasty (THA) are challenging to restore. Metal constructs for structural support are combined with bone graft materials for restoration. Autograft is restricted due to limited volume, and allogenic grafts have downsides including cost, availability, and operative processing. Bone graft substitutes (BGS) are an attractive alternative if they can demonstrate positive remodelling. One potential product is a biphasic injectable mixture (Cerament) that combines a fast-resorbing material (calcium sulphate) with the highly osteoconductive material hydroxyapatite. This study reviews the application of this biomaterial in large acetabular defects. Methods. We performed a retrospective review at a single institution of patients undergoing revision THA by a single surgeon. We identified 49 consecutive patients with large acetabular defects where the biphasic BGS was applied, with no other products added to the BGS. After placement of metallic acetabular implants, the BGS was injected into the remaining bone defects surrounding the new implants. Patients were followed and monitored for functional outcome scores, implant fixation, radiological graft site remodelling, and revision failures. Results. Mean follow-up was 39.5 months (36 to 71), with a significant improvement in post-revision function compared to preoperative function. Graft site remodelling was rated radiologically as moderate in 31 hips (63%) and strong in 12 hips (24%). There were no cases of complete graft site dissolution. No acetabular loosening was identified. None of the patients developed clinically significant heterotopic ossification. There were twelve reoperations: six patients developed post-revision infections, three experienced dislocations, two sustained periprosthetic femur fractures, and one subject had femoral component aseptic loosening. Conclusion. Our series reports bone defect restoration with the sole use of a biphasic injectable BGS in the periacetabular region. We did not observe significant graft dissolution. We emphasize that successful graft site remodelling requires meticulous recipient site preparation. Cite this article: Bone Jt Open 2022;3(12):991–997

Aims. There is a lack of biomaterial-based carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotics for bone infections. RIF is also known for causing rapid development of antibiotic resistance when given as monotherapy. This in vitro study evaluated a clinically used biphasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN). Methods. The CaS/HA composites containing RIF/GEN/VAN, either alone or in combination, were first prepared and their injectability, setting time, and antibiotic elution profiles were assessed. Using a continuous disk diffusion assay, the antibacterial behaviour of the material was tested on both planktonic and biofilm-embedded forms of standard and clinical strains of Staphylococcus aureus for 28 days. Development of bacterial resistance to RIF was determined by exposing the biofilm-embedded bacteria continuously to released fractions of antibiotics from CaS/HA-antibiotic composites. Results. Following the addition of RIF to CaS/HA-VAN/GEN, adequate injectability and setting of the CaS/HA composites were noted. Sustained release of RIF above the minimum inhibitory concentrations of S. aureus was observed until study endpoint (day 35). Only combinations of CaS/HA-VAN/GEN + RIF exhibited antibacterial and antibiofilm effects yielding no viable bacteria at study endpoint. The S. aureus strains developed resistance to RIF when biofilms were subjected to CaS/HA-RIF alone but not with CaS/HA-VAN/GEN + RIF. Conclusion. Our in vitro results indicate that biphasic CaS/HA loaded with VAN or GEN could be used as a carrier for RIF for local delivery in clinically demanding bone infections. Cite this article: Bone Joint Res 2022;11(11):787–802

Aims

Excision of chronic osteomyelitic bone creates a dead space which must be managed to avoid early recurrence of infection. Systemic antibiotics cannot penetrate this space in high concentrations, so local treatment has become an attractive adjunct to surgery. The aim of this study was to present the mid- to long-term results of local treatment with gentamicin in a bioabsorbable ceramic carrier.

Surgical site infections following spinal surgery profoundly influence continued treatment, significantly impacting psychological and economic dimensions and clinical outcomes. Its reported incidence varies up to 20%, with the highest incidence amongst neuromuscular scoliosis and metastatic cord compression patients. We describe the first reported biphasic osteoconductive scaffold (Cerament G) with a logarithmic elution profile as a cumulative strategic treatment modality for adjacent spinal surgery infections. All patients who developed surgical site infections following instrumented fusion (May 2021-December 2021) had their demographics (age, sex), type and number of procedures, isolated organism, antibiotics given, comorbidities, and WHO performance status analysed. The infected wound was debrided to healthy planes, samples taken, and Cerament g applied. Thirteen patients were treated for deep SSI following spinal instrumentation and fusion procedures with intraoperative Cerament G application. There were four males and nine females with an average age of 40 ranging between 12 and 87. Nine patients underwent initial surgery for spinal deformity, and four were treated for fractures as index procedure. 77% of infections were attributable to MSSA and Cutibacteriousm acnes; others included Klebsiella, Pseudomonas and Streptococcus and targeted with multimodal cumulative therapy. A WHO performance score improved in 11 patients. In addition, there was no wound leak, and infection was eradicated successfully in 12/13 with a single procedure. This series shows the successful eradication of the infection and improved functional outcomes with Cerament G. However, the low numbers of patients in our series are an essential consideration for the broader applicability of this device

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Thresholds of acceptable early migration of the components in total knee arthroplasty (TKA) have traditionally ignored the effects of patient and implant factors that may influence migration. The aim of this study was to determine which of these factors are associated with overall longitudinal migration of well-fixed tibial components following TKA.

Aims. The aim of this study was to compare any differences in the primary outcome (biphasic flexion knee moment during gait) of robotic arm-assisted bi-unicompartmental knee arthroplasty (bi-UKA) with conventional mechanically aligned total knee arthroplasty (TKA) at one year post-surgery. Methods. A total of 76 patients (34 bi-UKA and 42 TKA patients) were analyzed in a prospective, single-centre, randomized controlled trial. Flat ground shod gait analysis was performed preoperatively and one year postoperatively. Knee flexion moment was calculated from motion capture markers and force plates. The same setup determined proprioception outcomes during a joint position sense test and one-leg standing. Surgery allocation, surgeon, and secondary outcomes were analyzed for prediction of the primary outcome from a binary regression model. Results. Both interventions were shown to be effective treatment options, with no significant differences shown between interventions for the primary outcome of this study (18/35 (51.4%) biphasic TKA patients vs 20/31 (64.5%) biphasic bi-UKA patients; p = 0.558). All outcomes were compared to an age-matched, healthy cohort that outperformed both groups, indicating residual deficits exists following surgery. Logistic regression analysis of primary outcome with secondary outcomes indicated that the most significant predictor of postoperative biphasic knee moments was preoperative knee moment profile and trochlear degradation (Outerbridge) (R. 2. = 0.381; p = 0.002, p = 0.046). A separate regression of alignment against primary outcome indicated significant bi-UKA femoral and tibial axial alignment (R. 2. = 0.352; p = 0.029), and TKA femoral sagittal alignment (R. 2. = 0.252; p = 0.016). The bi-UKA group showed a significant increased ability in the proprioceptive joint position test, but no difference was found in more dynamic testing of proprioception. Conclusion. Robotic arm-assisted bi-UKA demonstrated equivalence to TKA in achieving a biphasic gait pattern after surgery for osteoarthritis of the knee. Both treatments are successful at improving gait, but both leave the patients with a functional limitation that is not present in healthy age-matched controls. Cite this article: Bone Joint J 2022;103-B(4):433–443

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Our objective was to conduct a systematic review and meta-analysis, to establish whether differences arise in clinical outcomes between autologous and synthetic bone grafts in the operative management of tibial plateau fractures.

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Large-diameter metal-on-metal (MoM) total hip arthroplasty (THA) has demonstrated unexpected high failure rates and pseudotumour formation. The purpose of this prospective cohort study is to report ten-year results in order to establish revision rate, prevalence of pseudotumour formation, and relation with whole blood cobalt levels.

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The aim of this study was to compare the clinical outcomes of robotic arm-assisted bi-unicompartmental knee arthroplasty (bi-UKA) with conventional mechanically aligned total knee arthroplasty (TKA) during the first six weeks and at one year postoperatively.

Abstract. Objectives. Assess and characterise the suitability of a novel silk reinforced biphasic 3D printed scaffold for osteochondral tissue regeneration. Methods. Biphasic hybrid scaffolds consisted of 3D printed poly(ethylene glycol)-terephthalate-poly(butylene terephthalate)(PEGT/PBT) scaffold frame work (pore size 0.75mm), which has been infilled with a cast and freeze dried porous silk scaffold (5×5×2mm. 3. ), in addition to a seamless silk top layer (1mm). Silk scaffolds alone were used as controls. Both the biphasic and control scaffolds were characterised via uniaxial compression testing (strain rate 0.1mm/min), and the potential biocompatibility of the scaffolds was tested via in vitro culture of seeded bone marrow stromal cells post fabrication. Results. Uniaxial compression testing showed that the biphasic scaffolds (N=4) initially demonstrated similar behaviour on a stress-strain curve to a silk scaffold alone control group (N=6), until a strain of 30% was reached. After 30% strain, load was transitioned from the silk only chondral layer to the 3D printed PEGT/PBT scaffold which resisted further compression and exhibited a significantly greater compressive modulus of 12.6±0.9MPa compared to 0.113±0.01MPa (p<0.001) in the silk scaffold control group. Following 24hours of seeding, no difference was noticed in cell adhesion behaviour under fluorescent microscopy between silk scaffolds and biphasic scaffolds (n=5). Discussion. The use of 3D printing within this novel scaffold provides a solid framework and increases its versatility. The reinforced silk not only provides the secondary Porous structure to the 3D printed scaffold for the bone phase, but also a superficial layer for the cartilage phase. This unique structure has the potential to fill a niche within osteochondral tissue regeneration, especially with the possibility for its use within personalised medicine. Conclusions. These results demonstrate that the novel silk reinforced biphasic 3D printed scaffold is biocompatible and has suitable mechanical properties for osteochondral tissue regeneration. 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