Introduction. A significant burden of disease exists with respect to critical sized bone defects; outcomes are unpredictable and often poor. There is no absolute agreement on what constitutes a “critically-sized” bone defect however it is widely considered as one that would not heal spontaneously despite surgical stabilisation, thus requiring re-operation. The aetiology of such defects is varied. High-energy trauma with soft tissue loss and periosteal stripping, bone infection and tumour resection all require extensive debridement and the critical-sized defects generated require careful consideration and strategic management. Current management practice of these defects lacks consensus. Existing literature tells us that tibial defects 25mm or great have a poor natural history; however, there is no universally agreed management strategy and there remains a significant evidence gap. Drawing its origins from musculoskeletal oncology, the Capanna technique describes a hybrid mode of reconstruction. Mass allograft is combined with a vascularised fibula autograft, allowing the patient to benefit from the favourable characteristics of two popular reconstruction techniques. Allograft confers initial mechanical stability with autograft contributing osteogenic, inductive and conductive capacity to encourage union. Secondarily its inherent vascularity affords the construct the ability to withstand deleterious effects of stressors such as infection that may threaten union. The strengths of this hybrid construct we believe can be used within the context of critical-sized bone defects within tibial trauma to the same success as seen within tumour reconstruction. Methodology. Utilising the Capanna technique in trauma requires modification to the original procedure. In tumour surgery pre-operative cross-sectional imaging is a pre-requisite. This allows surgeons to assess margins, plan resections and order allograft to match the defect. In trauma this is not possible. We therefore propose a two-stage approach to address critical-sized tibial defects in open fractures. After initial debridement, external fixation and soft tissue management via a combined orthoplastics approach, CT imaging is performed to assess the defect geometry, with a polymethylmethacrylate (PMMA) spacer placed at index procedure to maintain soft tissue tension, alignment and deliver local antibiotics. Once comfortable that no further debridement is required and the risk of infection is appropriate then 3D printing technology can be used to mill custom jigs. Appropriate tibial allograft is ordered based on CT measurements. A pedicled fibula graft is raised through a lateral approach. The peroneal vessels are mobilised to the tibioperoneal trunk and passed medially into the bone void. The cadaveric bone is prepared using the custom jig on the back table and posterolateral troughs made to allow insertion of the fibula, permitting some hypertrophic expansion. A separate medial incision allows attachment of the custom jig to host tibia allowing for reciprocal cuts to match the allograft. The fibula is implanted into the allograft, ensuring nil tension on the pedicle and, after docking the graft, the hybrid construct is secured with multi-planar locking plates to provide rotational stability. The medial window allows plate placement safely away from the vascular pedicle. Results. We present a 50-year-old healthy male with a Gustilo & Anderson 3B proximal tibial fracture, open posteromedially with associated shear fragment, treated using the Capanna technique. Presenting following a fall climbing additional injuries included a closed ipsilateral calcaneal and medial malleolar fracture, both treated operatively. Our patient underwent reconstruction of his tibia with the above staged technique. Two debridements were carried out due to a 48-hour delay in presentation due to remote geographical location of recovery. Debridements were carried out in accordance with BOAST guidelines; a spanning knee external fixator applied and a small area of skin loss on the proximal medial calf reconstructed with a split thickness skin graft. A revision cement spacer was inserted into the metaphyseal defect measuring 84mm. At definitive surgery the external fixator was removed and graft fixation was extended to include the intra-articular fragments. No intra-operative complications were encountered during surgeries. The patient returned to theatre on day 13 with a medial sided haematoma. 20ml of haemoserous fluid was evacuated, a DAIR procedure performed and antibiotic-loaded bioceramics applied locally. Samples grew Staphylococcus aureus and antibiotic treatment was rationalised to Co-Trimoxazole 960mg BD and Rifampicin 450mg BD. The patient has completed a six-week course of Rifampicin and continues on suppressive Co-Trimoxazole monotherapy until planned metalwork removal. There is no evidence of ongoing active infection and radiological evidence of early union. The patient is independently walking four miles to the gym daily and we believe, thus far, despite accepted complications, we have demonstrated a relative early success. Conclusions. A variety of techniques exist for the management of critical-sized bone defects within the tibia. All of these come with a variety of drawbacks and limitations. Whilst acceptance of a limb length discrepancy is one option, intercalary defects of greater than 5 to 7cm typically require reconstruction. In patients in whom fine wire fixators and distraction osteogenesis are deemed inappropriate, or are unwilling to tolerate the frequent re-operations and potential donor site morbidity of the Masqualet technique, the Capanna technique offers a novel solution. Through using tibial allograft to address the size mismatch between vascularised fibula and tibia, the possible complication of fatigue fracture of an isolated fibula autograft is potentially avoidable in patients who have high functional demands. The Capanna technique has demonstrated satisfactory results within tumour reconstruction. Papers report that by combining the structural strength of allograft with the osteoconductive and osteoinductive properties of a vascularised autograft that limb salvage rates of greater than 80% and union rates of greater than 90% are achievable. If these results can indeed be replicated in the management of critical-sized bone defects in tibial trauma we potentially have a treatment strategy that can excel over the more widely practiced current techniques

The Cierny and Mader classification assists with decision-making in the management of osteomyelitis by strafying the host status and the pathoanatomy of disease. However the anatomical type IV represents a heterogenous group with regards to treatment requirements and outcomes. We propose that modification of the Cierny and Mader anatomical classification with an additional type V classifier (diffuse corticomedullary involvement with an associated critical bone defect) will allow more accurate stratification of patients and tailoring of treatment strategies. A retrospective review of 83 patients undergoing treatment for Cierny and Mader anatomical type IV osteomyelitis of the appendicular skeleton at a single centre was performed. Risk factors for the presence of a critical bone defect were female patients (OR 3.1 (95% CI 1.08– 8.92)) and requirement for soft tissue reconstruction (OR 3.35 (95% CI 1.35–8.31)); osteomyelitis of the femur was negatively associated with the presence of a critical bone defect (OR 0.13 (95% CI 0.03–0.66)). There was no statistical significant risk of adverse outcomes (failure to eradicate infection or achieve bone union) associated with the presence of a critical-sized bone defect. The median time to bone union was ten months (95% CI 7.9–12.1 months). There was a statistically significant difference in the median time to bone union between cases with a critical bone defect (12.0 months (95% 10.2–13.7 months)) and those without (6.0 months (95% CI 4.8–7.1 months)). This study provided evidence to support the introduction of a new subgroup of the Cierny and Mader anatomical classification (Type V). Using a standardised approach to management, comparable early outcomes can be achieved in patients with Cierny and Mader anatomical type V osteomyelitis. However, to achieve a successful outcome, there is a requirement for additional bone and soft tissue reconstruction procedures with an associated increase in treatment time

Introduction. The Cierny and Mader classification assists with decision-making by stratifying host status and the pathoanatomy of the disease. However, the anatomical type IV represents a heterogenous group with regards to treatment requirements and outcomes. We propose that modification of the Cierny and Mader anatomical classification with an additional type V classifier (diffuse corticomedullary involvement with an associated critical bone defect) will allow more accurate stratification of patients and tailoring of treatment strategies. Materials & Methods. A retrospective review of 83 patients undergoing treatment for Cierny and Mader anatomical type IV osteomyelitis of the appendicular skeleton at a single centre was performed. Results. Risk factors for the presence of a critical bone defect were female patients (OR 3.1 (95% CI 1.08–8.92)) and requirement for soft tissue reconstruction (OR 3.35 (95% CI 1.35–8.31)); osteomyelitis of the femur was negatively associated with the presence of a critical bone defect (OR 0.13 (95% CI 0.03–0.66)). There was no statistically significant risk of adverse outcomes (failure to eradicate infection or achieve bone union) associated with the presence of a critical-sized bone defect. The median time to bone union was ten months (95% CI 7.9–12.1 months). There was a statistically significant difference in the median time to bone union between cases with a critical bone defect (12.0 months (95% 10.2–13.7 months)) and those without (6.0 months (95% CI 4.8–7.1 months)). Conclusions. This study provided evidence to support the introduction of a new subgroup of the Cierny and Mader anatomical classification (Type V). Using a standardised approach to management, comparable early outcomes can be achieved in patients with Cierny and Mader anatomical type V osteomyelitis. However, to achieve a successful outcome, there is a requirement for additional bone and soft tissue reconstruction procedures with an associated increase in treatment time

Aim. The primary endpoint of this study is to characterize the progression of bone defects at the femoral and tibial side in patients who sustained PJI of the knee that underwent two-stage revision with spacer implantation. In addition, we want to analyze the differences between functional moulded and hand-made spacers. Methods. A retrospective analysis of patients that underwent two-stage revision due to PJI of the knee between January 2014 and December 2021 at our institution. Diagnosis of infection was based on the criteria of the Muscoloskeletal Infection Society. The bone defect evaluation was performed intraoperatively based on the AORI classification. The basal evaluation was performed at the time the resection arthroplasty and spacer implantation surgery. The final evaluation was performed at the second-stage surgery, at the time of spacer removal and revision implant positioning. The differences between groups were characterized by using T-test student for continuous variables, and by using chi-square for categorical variables. A p-value < 0.05 was defined as significant. Results. Complete data of 37 two-stage TKAs revision were included in the study. An articulating moulded functional spacer was used in 14 (35.9%) cases, while a hand-made spacer was used in 23 (58.9%) cases. The average length of interval period (excluding the time for patients that retained the spacer) was 146.6 days. A bone defects progression based on the AORI classification was documented in 24 cases at the femoral side (61.6%), a bone defect progression was documented in 17 cases at the tibial side (43.6%), and a bone defect at both sides was documented in 13 cases (33.3%). A statistically significant greater bone defect progression at the tibial side was observed when hand-made spacers were used. A complication during the interval period was reported in five cases (12.8%) and postoperative complication was reported in 9 cases (23.1%). Conclusions. When comparing patients in which a functional articulating spacer was used, with patients in which static spacer was used, we reported a statistically significant reduced bone defect progression during the interval period at the femoral side only when moulded spacers were used. We observed a higher incidence of bone defect progression also at the tibial and both sides when hand-made spacers were used. This is the first study that documented the bone defect progression during two-stage revision of the knee, the results observed in this study are very encouraging

Osteoarthritis (OA) is one of the most prevalent joint diseases involving progressive and degenerative changes to cartilage resulting from a variety of etiologies including post-traumatic incident or aging. OA lesions can be treated at its early stages through cell-based tissue engineering therapies using Mesenchymal Stem Cells (MSCs). In vivo models for evaluating these strategies, have described both chondral (impaction) and osteochondral (biopsy punch) defects. The aim of the investigation was to develop a compact and reproducible defect inducing post-traumatic degenerative changes mimicking early OA. Additionally, a pilot study to evaluate the efficacy of MSC-hydrogel treatment was also assessed. Surgery was performed on New Zealand white rabbits (male, 5–8 months old) with defects created on medial femoral condyle. For developing an appropriate defect, three approaches were used for evaluation: a biopsy punch (n = three at six and twelve weeks), an impaction device1 (n = three at six and twelve weeks) and a dental drill model (n = six at six and twelve weeks). At stated time points, condyles were harvested and decalcified in 10% EDTA, then embedded in Tissue-Tek and sectioned using a cryostat. Upon identification of region of interest, sections were stained with Safranin-O/Fast green and scored using OARSI scoring system by two blinded observers2. For the pilot study, autologous bone marrow was harvested from rabbits and used to isolate and expand MSCs. The Dental drill model was applied to both knee condyles, left untreated for six weeks at which stage, PKH26 fluorescently labelled MSCs were seeded into a hyaluronic acid hydrogel (TETEC). Repair tissue was removed from both condyles and MSC-hydrogel was injected into the left knee, whilst right knee was left empty. Rabbits were sacrificed at one (n = 1), six (n = 3) and twelve (n = 3) weeks post-treatment, processed as previously described and cartilage regeneration evaluated using Sellers score3. Impacted condyles exhibited no observed changes histologically (Mean OARSI score = 1 + 1), whereas biopsy punched and dental drilled defects demonstrated equal signs of cartilage erosion (OARSI score = 3 + 1) at assessed time points. However, biopsy punched condyles formed a diffusive defect, whereas dental drilled condyles showed a more defined, compact and reproducible defect. In the pilot study, PKH-labelled MSCs were observed at one and six weeks post-implantation within the defect space where hydrogel was injected. Tissue regeneration assessment indicated no difference between empty (Mean Sellers score = 14 + 2) and MSC treated defects (Sellers score = 16 + 5) at six weeks post-injection. At twelve weeks, MSC treated defects showed improved tissue regeneration with substantial subchondral bone restoration and good integration of regenerative cartilage with surrounding intact tissue (Sellers score = 10 + 1), whereas untreated defects showed no change in regeneration compared to six weeks (Sellers score = 16 + 2). Dental drill model was found to be the appropriate strategy for investigating early OA progression and treatment. Application of MSCs in defects showed good cartilage regeneration after twelve weeks application, indicating their promise in the treatment of early OA defects

Aim. Reconstruction of composite soft-tissue defects with extensor apparatus deficiency in patients with periprosthetic joint infection (PJI) of the knee is challenging. We present a single-centre multidisciplinary orthoplastic treatment concept based on a retrospective outcome analysis over 20 years. Method. One-hundred sixty-seven patients had PJI after total knee arthroplasty. Plastic surgical reconstruction of a concomitant perigenicular soft-tissue defect was indicated in 49 patients. Of these, seven presented with extensor apparatus deficiency. Results. One patient underwent primary arthrodesis and six patients underwent autologous reconstruction of the extensor apparatus. The principle to reconstruct missing tissue ‘like with like’ was thereby favoured: Two patients with a wide soft-tissue defect received a free anterolateral thigh flap with fascia lata; one patient with a smaller soft-tissue defect received a free sensate, extended lateral arm flap with triceps tendon; and three patients received a pedicled medial sural artery perforator gastrocnemius flap, of which one with Achilles tendon. Despite good functional results 1 year later, long-term follow-up revealed that two patients had to undergo knee arthrodesis because of recurrent infection and one patient was lost to follow-up. In parts, results have been published under doi: 10.7150/jbji.47018. Conclusions. A treatment concept and its rationale, based on a single-centre experience, is presented. It differentiates between various types of soft-tissue defects and shows reconstructive options following the concept to reconstruct ‘like with like’. Despite good results 1 year postoperatively, PJI of the knee with extensor apparatus deficiency remains a dreaded combination with a poor long-term outcome

Introduction. Primary stability is an important factor for long-term implant survival in total hip arthroplasty. In revision surgery, implant fixation becomes especially challenging due the acetabular bone defects, which are often present. Previous studies on primary stability of revision components often applied simplified geometrical defect shapes in a variety of sizes and locations. The objectives of this study were to (1) develop a realistic defect model in terms of defect volume and shape based on a clinically existing acetabular bone defect, (2) develop a surrogate acetabular test model, and (3) exemplarily apply the developed approach by testing the primary stability of a pressfit-cup with and without bone graft substitute (BGS). Materials & Methods. Based on clinical computed tomography data and a method previously published [1], volume and shape information of a representative defect, chosen in consultation with four senior hip revision surgeons, was derived. Volume and shape of the representative defect was approximated by nine reaming procedures with hemispherical acetabular reamers, resulting in a simplified defect with comparable volume (18.9 ml original vs. 18.8 ml simplified) and shape. From this simplified defect (Defect D), three additional defect models (Defect A, B, C) were derived by excluding certain reaming procedures, resulting in four defect models to step-wise test different acetabular revision components. A surrogate acetabular model made of 20 PCF polyurethane foam with the main support structures was developed [2]. For the exemplary test, three series for Defect A were defined: Native (acetabulum without defect), Empty (defect acetabulum without filling), Filled (defect acetabulum with BGS filling). All series were treated with a pressfit-cup and subjected to dynamic axial load in direction of maximum resultant force during level walking. Minimum load was 300 N and maximum load was increased step-wise from 600 N to 3000 N. Total relative motion between cup and foam, consisting of inducible displacement and migration, was assessed with the optical measurement system gom Aramis (gom GmbH, Braunschweig, DE). Results. Total relative motion increased with increasing load, with a maximum of 0.63 mm for Native, 0.86 mm for Filled, and 1.9 mm for Empty. At load stage 1800 N, total relative motion in Empty was 11.0-fold increased in comparison to Native, but could be reduced to a 3.3-fold increase in Filled. Discussion. The objective of this study was to develop a simplified, yet realistic and modular defect model which could be used to step-wise test different treatment strategies. Applicability of the developed test setup was shown by assessing primary stability of a pressfit-cup in a native, empty, and filled situation. The presented method could potentially be used as a modular test setup to compare different acetabular revision components in a standardized way. For any figures or tables, please contact authors directly

Treatment of segmental bone defects remains a major clinical problem, and innovative strategies are often necessary to successfully reconstruct large volumes of bone. When fractures occur, the resulting hematoma serves as a reservoir for growth factors and a space for cell infiltration, both crucial to the initiation of bone healing. Our previous studies have demonstrated very clear ultrastructural differences between fracture hematomas formed in normally healing fractures and those formed in segmental bone defects. However, there is little information available regarding potential differences in the underlying gene expression between hematomas formed in normal fractures, which usually heal by themselves, and segmental bone defects, which do not. Therefore, the aim of this study was to identify differences in gene expression within hematomas collected from 0.5 mm (normal fracture) and 5 mm (segmental bone defect) fracture sites during the earliest stages of bone healing. Osteotomies of 0.5 and 5 mm in the femur of Fisher 344 rats were stabilized with external fixators (RISystem AG). After 3 days the rats were sacrificed, and the fracture hematomas were collected for RNA-sequencing. Ingenuity pathway analysis (IPA) was used to identify upstream regulators and biological functions that were significantly enriched with differentially expressed genes from the RNA-sequencing analysis. Animal procedures were conducted following the IACUC protocol of the UT Health Science Center San Antonio. Key upstream regulators of bone formation were less active (e.g. TGFB1, FGF2, SMAD3) or even inhibited (e.g. WNT3A, RUNX2, BMP2) in non-healing defects when compared to normally healing fractures. Many upstream regulators that were uniquely enriched in healing defects were molecules recently discovered to have osteogenic effects during fracture healing (e.g. GLI1, EZH2). Upstream regulators uniquely enriched in non-healing defects were mainly involved in an abnormal modulation of hematopoiesis, revealing evidence of impaired maturation of functional macrophages and cytokines (e.g. IL3, CEBPE), both essential for successful bone healing. In addition, the enrichment pattern suggested a dysregulation of megakaryopoiesis (e.g. MRTFA, MRTFB, GATA2), which directly affects platelet production, and therefore fracture hematoma formation. Remarkably, the organization of the ECM was the most significantly enriched biological function in the normally healing fractures, and implies that the defect size directly affected the structural properties within the fracture hematoma. Conversely, genes encoding important ECM components (e.g. BGN, various collagens, IBSP, TNC), cell adhesion molecules, MMPs (MMP2), and TIMPs were all significantly downregulated in non-healing defects. Our most recent findings reveal new important key molecules that regulate defect size-dependent fracture healing. Combined with our previous results, which identified structural differences in fracture hematomas from both types of defects, current findings indicate that differential expression of genes is dictated by the structural properties of the hematomas formed during early fracture healing. Consequently, creating a bioscaffold that mimics the structure of normal fracture hematomas could be the first step towards developing new orthoregenerative treatment strategies that potentiate healing of large bone defects and non-healing fractures

Introduction. Acetabular bone defects are still challenging to quantify. Numerous classification schemes have been proposed to categorize the diverse kinds of defects. However, these classification schemes are mainly descriptive and hence it remains difficult to apply them in pre-clinical testing, implant development and pre-operative planning. By reconstructing the native situation of a defect pelvis using a Statistical Shape Model (SSM), a more quantitative analysis of the bone defects could be performed. The aim of this study is to develop such a SSM and to validate its accuracy using relevant clinical scenarios and parameters. Methods. An SSM was built on the basis of segmented 66 CT dataset of the pelvis showing no orthopedic pathology. By adjusting the SSM's so called modes of shape variation it is possible to synthetize new 3D pelvis shapes. By fitting the SSM to intact normal parts of an anatomical structure, missing or pathological regions can be extrapolated plausibly. The validity of the SSM was tested by a Leave-one-out study, whereby one pelvis at a time was removed from the 66 pelvises and was reconstructed using a SSM of the remaining 65 pelvises. The reconstruction accuracy was assessed by comparing each original pelvis with its reconstruction based on the root-mean-square (RMS) surface error and five clinical parameters (center of rotation, acetabulum diameter, inclination, anteversion, and volume). The influence of six different numbers of shape variation modes (reflecting the degrees of freedom of the SSM) and four different mask sizes (reflecting different clinical scenarios) was analyzed. Results. The Leave-one-out study showed that the reconstruction errors decreased when the number of shape variation modes included in the SSM increased from 0 to 20, but remained almost constant for higher numbers of shape variation modes. For the SSM with 20 shape variation modes, the RMS of the reconstruction error increased with increasing mask size, whereas the other parameters only increased from Mask_0 to Mask_1, but remained almost constant for Mask_1, Mask_2 and Mask_3. Median reconstruction errors for Mask_1, Mask_2, and Mask_3 were approximately 3 mm in Center of Rotation (CoR) position, 2 mm in Diameter, 3° in inclination and anteversion, as well as 5 ml in volume. Discussion. This is the first study analyzing and showing the feasibility of a quantitative analysis of acetabular bone defects using a SSM-based reconstruction method in the clinical scenario of a defect or implant in both acetabuli and incomplete CT-scans. Validation results showed acceptable reconstruction accuracy, also for clinical scenarios in which less healthy bone remains. Further studies could apply this method on a larger number of defect pelvises to obtain quantitative measures of acetabular bone defects

Uncontained acetabular defects with loss of superior iliac and posterior column support (Paprosky 3) represent a reconstructive challenge as the deficient bone will preclude the use of a conventional hemispherical cup. Such defects can be addressed with large metallic constructs like cages with and without allograft, custom tri-flange cups, and more recently with trabecular metal augments. An underutilised alternative is impaction bone grafting, after creating a contained cavitary defect with a reinforcement mesh. This reconstructive option delivers a large volume of bone while using a small-size socket fixed with acrylic cement. Between 2005 and 2014, 21 patients with a Paprosky 3B acetabular defect were treated with cancellous, fresh frozen impaction grafting supported by a peripheral reinforcement mesh secured to the pelvis with screws. A cemented all-polyethylene cup was used. Pre-operative diagnosis was aseptic loosening (15 cemented and 6 uncemented). The femoral component was revised in 10 patients. Post-operative course consisted of 3 months of protected weight bearing. Patients were followed clinically and radiographically. One patient had an incomplete post-operative sciatic palsy. After a mean follow up of 47 months (13 to 128) none of the patients required re-revision of the acetabular component. One asymptomatic patient presented with aseptic loosening 9 years post-operatively. Hardware failure was not observed. All patients had radiographic signs of graft incorporation and bone remodeling. There were no dislocations. The early and mid-term results of revisions of large acetabular defects with this technique are encouraging. Reconstitution of hip center of rotation and bone stock with the use of a small-size implant makes this technique an attractive option for large defects. Longer follow-up is needed to assess survivability

The Masquelet or induced membrane technique (IMT) is a two-stage surgical procedure used for the treatment of segmental bone defects. In this technique, the defect is first filled with a polymethyl methacrylate (PMMA) spacer, which triggers the formation of a membrane that will encapsulate the defect. During the second surgery, the spacer is carefully removed and replaced by autologous bone graft while preserving the membrane. This membrane is vascularized, contains growth factors, and provides mechanical stability to the graft, all of which are assumed to prevent graft resorption and promote bone healing. The technique is gaining in popularity and several variations have been introduced in the clinical practice. For instance, orthopaedic surgeons now often include antibiotics in the spacer to treat or prevent infection. However, the consequences of this approach on the properties of the induce membrane are not fully understood. Accordingly, in a small animal model, this study aimed to determine the impact on the induced membrane of impregnating spacers with antibiotics frequently used in the IMT. We surgically created a five-mm segmental defect in the right femur of 25 adult male Sprague Dawley rats. The bone was stabilized with a plate and screws before filling the defect with a PMMA spacer. Animals were divided into five equal groups according to the type and dose of antibiotics impregnated in the spacer: A) no antibiotic (control), B) low-dose tobramycin (1.2 g/40 g of PMMA), C) low-dose vancomycin (1 g/40 g of PMMA), D) high-dose tobramycin (3.6 g/40 g of PMMA), E) high-dose vancomycin (3 g/40 g of PMMA). The animals were euthanized three weeks after surgery and the induced membranes were collected and divided for analysis. We assessed the expression of selected genes (Alpl, Ctgf, Runx2, Tgfb1, Vegfa) within the membrane by quantitative real-time PCR. Moreover, frozen sections of the specimens were used to quantify vascularity by immunohistochemistry (CD31 antigen), proliferative cells by immunofluorescence (Ki-67 antigen), and membrane thickness. Microscopic images of the entire tissue sections were taken and analyzed using FIJI software. Finally, we measured the concentration of vascular endothelial growth factor (VEGF) in the membranes by ELISA. No significant difference was found among the groups regarding the expression of genes related to osteogenesis (Alpl, Runx2), angiogenesis (Vegfa), or synthesis of extracellular matrix (Ctgf, Tgfb1) (n = four or five). Similarly, the density of proliferative cells and blood vessels within the membrane, as well as the membrane thickness, did not vary substantially between the control, low-dose, or high-dose antibiotic groups (n = four or five). The concentration of VEGF was also not significantly influenced by the treatment received (n = four or five). The addition of tobramycin or vancomycin to the spacer, at the defined low and high doses, does not significantly alter the bioactive characteristics of the membrane. These results suggest that orthopaedic surgeons could use antibiotic-impregnated spacers for the IMT without compromising the induced membrane and potentially bone healing

Purpose. The aim of this study was to assess the clinical and radiological result of the usage of chip bone graft in non-contained type bone defect in primary or revision total knee arthroplasty patients. Subjects and Methods. We investigated 32 patients who had underwent primary or revision total knee arthroplasty from March, 2014 to February, 2017 in our hospital, who had non-contained type of defect. The mean age was 73.1 years. 5 of them were males, while 27 of them were females. 7 of them were primary total knee arthroplasty patients, while 25 of them were revision patients. 8 of them had chip bone graft used both in the femur and tibia. 9 of them had chip bone graft used only in the tibia. The other 15 had chip bone graft used only in the femur. Wire-mesh was used in the 9 patients who had chip bone graft used only in the medial side of the tibia. We used KOOS (Knee injury and osteoarthritis outcome score), HSS (Hospital for Special Surgery knee service rating system) and WOMAC scores to assess the clinical result, before the surgery and at the last follow-up. In addition, we had follow-up x-rays and 3D CT done for the patients to check the mean bone union period. In addition, overall radiologic imaging studies were used for complications such as loosening, osteolysis and lesions with radiolucency. Result. The Mean follow-up period was 2.7 years (range; 2.1 to 5). The Mean preoperative KOOS was 102.8 (range; 47 to 132), while it became 31.8 postoperatively (range; 20 to 45). The mean HSS was 13.1 (range; 6 to 35), while it became 35.9 postoperatively (range; 24 to 64). The mean WOMAC was 82.9 (range; 62 to 92), while it became 22.5 postoperatively (range; 13 to 30). According to follow-up x-ray and CT, the mean bone union period was 10.6 months (range: 10 to 13). In follow-up 3D CT of all cases, we could check cortical healing and new bone formation, seen as medium to high-attenuating conglomerate. The graft-host junction showed trabecular ingrowth, while the medullary canal showed fibrous ingrowth. Radiologically, there was no complication such as loosening, osteolysis, migration and radiolucent lines around the stems or cement mantles. In addition, there was no complication such as infection. Conclusion. Chip bone graft is not a commonly used method for bone defect in total knee arthroplasty. According to the result of the usage of chip bone graft in primary or revision total knee arthroplasty with non-contained type of bone defect, it showed favorable result for the subject patients. Therefore, we can consider it as one of the effective methods to manage non-contained bone defect in knee arthroplasty. Keywords. Revision TKA, chip bone graft, wire-mesh, non-contained bone defect. For any figures or tables, please contact authors directly

Purpose. The aim of this study was to compare the clinical outcomes of the revision TKA in which trabecular metal cones and femoral head allografts were used for large bone defect. Method. Total 53 patients who have undergone revision TKA from July 2013 to March 2017 were enrolled in this study. Among them, 24 patients used trabecular metal cones, and 29 patients used femoral head allografts for large bone defect. There were 3 males and 21 females in the metal cone group, while there were 4 males and 25 females in the allograft group. The mean age was 70.2 years (range, 51–80) in the femoral head allograft group, while it was 79.1 years (range, 73–85) in the metal cone group. Bone defect is classified according to the AORI classification and clinical outcomes were evaluated with Visual Analogue Scale (VAS), Hospital Special Surgery-score (HSS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Injury and Osteoarthritis Outcome Score (KOOS), and ROM. Operation time was also evaluated. We used radiographs to check complications such as migration or loosening. We took follow-up x-rays and 3D CT of the patients, to assess the mean bone union period. Shapiro-Wilk test was done to check normality and Student T-test and Mann Whitney U-test were done for comparison between two groups. Result. The mean follow-up period was 3 .75 years (Range; 2.1 ∼ 5.75). The pre-op scores did not show significant difference. The mean VAS in the allograft and trabecular metal cone groups was 2.1 ± 0.87 and 1.8 ± 0.53, respectively (p = 0.16). The mean HSS score were 76.3 ± 5.51 and 79.2 ± 4.12 respectively (p = 0.13) and the mean WOMAC scores were 15.1 ± 3.25 and 14.8 ± 3.31 respectively (p = 0.06), and the mean KOOS scores were 27.8 ± 4.77 and 25.5 ± 4.84, respectively (p = 0.07). The mean ROM ranges were 100.6 ± 17.54 and 101.3 ± 19.22, respectively (p = 0.09). But the mean operation time of the allograft and trabecular metal cone groups was 137 minutes (Range; 111–198) and 102minutes (Range; 93 −133) (p=0.02) respectively, which showed statistical significance. In follow-up x-rays, no migration or loosening of the implants, osteolysis and other complications were found in both groups. In follow-up 3D CT, osteointegration was seen at the trabecular metal cone site, host bone being interpreted to the host bone. The allograft group showed fibrous and stable union in follow-up 3D CT. Conclusion. According to this study, in case of revision TKA with large bone defect, using whether allograft or trabecular metal cones did not affect the clinical outcomes. However, operation time was significantly shorter in trabecular metal cone group, therefore, in patients with poor general condition along with severe underlying diseases, usage of trabecular metal cone would be a better choice to shorten operation time and ease postoperative care. Keywords. Revision TKA, metal cone, allograft, bone defect. For any figures or tables, please contact authors directly

INTRODUCTION. Appropriate, well characterized animal models remain essential for preclinical research. This study investigated a relevant animal model for cancellous bone defect healing. Three different defect diameters of fixed depth were compared in both skeletally immature and mature sheep. This ovine model allows for the placement of four confined cancellous defects per animal. METHODS. Defects were surgically created and placed in the cancellous bone of the medial distal femoral and proximal tibial epiphyses (See Figure 1). All defects were 25 mm deep, with defect diameters of 8, 11, and 14 mm selected for comparison. Defects sites were flushed with saline to remove any residual bone particulate. The skeletally immature and mature animals corresponded to 18 month old and 5 year old sheep respectively. Animals were euthanized at 4 weeks post-operatively to assess early healing. Harvested sites were graded radiographically. The percentage of new bone volume within the total defect volume (BV/TV) was quantified through histomorphometry and μ-CT bone morphometry. Separate regions of interest were constructed within the defect to assess differences in BV/TV between periosteal and deep bone healing. Defect sites were PMMA embedded, sectioned, and stained with basic fuschin and methylene blue for histological evaluation. RESULTS. The animals tolerated the surgery well, with no incidence of fractures within the four weeks. Healing of the defects progressed via endochondral ossification, with none of the defects being completely healed within the 4 week time point. Bone volume fraction (BV/TV) significantly decreased with an increasing defect diameter. Actual bone volume (BV), however, increased with defect diameter, suggesting a correlation between biological response and severity of injury. Three distinct healing regions were found to exist within the defect and along the axis of the defect, with significant differences detected in the BV/TV between adjacent regions. Histologically, the 5 year old animals appeared to have decreased osteoblast activity, and lower osteocyte density within the newly formed woven bone. On occasion, the defects were found to intersect the tibial growth plate in the 18 month old animals, with bone replacing the proliferating chondrocyte zone (See Figure 2). Additionally, the 14 mm defect was not able to be placed in the tibia of sheep due to the possibility of the defect entering the tibial intramedullary (IM) canal, and the lack of cancellous bone between the tibial plateau and IM canal. Both these issues considerably affect this model and should be avoided. CONCLUSION. The surgical placement of 11 mm diameter defects in the proximal tibial and distal femoral epiphyses of skeletally mature sheep presents a suitable large animal model to study early healing of cancellous bone defects. This refined model allows for the placement of four separate non-healing defects within a single sheep, and allows for the possibility to reduce animal numbers required to obtain information

Introduction. Modern acetabular cups require a convenient bone stock for sufficient cup fixation. Thereby, fixation stability is influenced by the chosen interference fit of the acetabular cup, the cup surface structure, circularity of the reamed acetabulum and by the acetabular bone quality. The ideal implantation situation of the cup is commonly compromised by joint dysplasia and acetabular bone defects. The aim of the present experimental study was to characterise implant fixation of primary acetabular cups in case of definite acetabular cavity defects. Materials and Methods. For the experimental determination bone substitute blocks (100 × 100 × 50 mm) made of polymethacrylimide (PMI) foam with a density of 7 pcf were used. The created acetabular defect situations were derived from the defect classification according to Paprosky. The defect geometries in the PMI foam blocks were realised by a CNC drilling machine. Thereby the defects are described in the dorso-ventral direction by the angle α and in medio-lateral direction by the angle β (given as angle combination α/β) related to the centre of rotation of the reamed cavity. For the lever-out tests the defect types IIb and IIIa (each with different α and β angles) were considered and compared to the intact fixation situation. Therefore, a macrostructured titanium cup (Allofit, Zimmer GmbH, Wintherthur, Switzerland) with an outer diameter of 56 mm were displacement-controlled (v = 20 mm/min) pushed into the 2 mm diametric under reamed PMI-foam cavities. Three cups were inserted until the cup overhang pursuant to surgical technique was reached. Subsequently the cups were displacement-controlled (v = 20 mm/min) levered out via a rod which was screwed into the implant pole by perpendicular displacement (U. axial. ) of the rod in direction of the defect aperture. The lever-out moments were calculated by multiplying the first occurring force maximum (F. max. ) with the effective lever arm length (l. lever. ), whereby moments caused by the deadweight of the rod were considered. Primary stability was defined by the first maximum lever-out moment. Results. The calculated lever-out moments were in a range from 15.5 ± 1.4 Nm to 1.4 ± 0.5 Nm. Defects with a 90° dorso-ventral opening angle showed 57 ± 17% lower lever-out moments. Defects with a 120° dorso-ventral opening angle showed 80 ± 6% lower lever-out moments compared to the cup fixation into intact cavities. Moreover, medio-lateral angles greater than 20° reduced the lever-out moment by 79 ± 12% compared to the intact cavities. Conclusion. The determined lever-out moments underline the reduction of fixation stability of acetabular cup by loss of circumferential rim and absent of superior wall support of the acetabular bone. Thereby, the fixation stability is influenced by the degree of dorso-ventral and medio-lateral defect manifestation. Hence, the fixation stability depends on the cavity surface and in particular the surface of the bone-implant interface in the fixation zone of the acetabular cup Thus, dorso-ventral defect sizes with greater opening angle than 60° and medio-lateral defect sizes greater than 20° are critically for sufficient fixation of primary acetabular cup implants

Although total hip arthroplasty is highly successful for treatment of osteoarthrosis of hip joint, it is skill demanding surgery to perform and even more challenging in case of revision with bone defects. There are many options available for reconstruction of acetabular bony defects. Here, we evaluate the outcome of acetabular bony defect reconstructed with trabecular metal augments in short term. We performed, 22 revision total hip arthroplasties and 6 primary total hip arthroplasties (total 28 in 28 patients) using trabecular metal augments to reconstruct acetabular defect between 2011 to 2015. Out of these 28 patients, 18 were males and 10 were females. Mean age of these patients was 61.2 years (range: 46 years to 79 years). Pre-operative templating was done for all cases and need for trabecular metal augments was anticipated in all cases. All cases were classified according to Paprosky classification for acetabular bone defects. Out of 28 patients, 3 had type 2B, 1 had type 2C, 18 had type 3A and 6 had type 3B acetabular defects. Post operatively, all patients were followed at regular interval for their clinical and radiological outcome. An average follow up was 20.1 months (range: 6 months to 42.5 months). We assessed clinical outcome in the form of Herris hip score (HHS) and radiological outcomes in form of osteolysis in acetabular zones and osseointegration, according to the criteria of Moore. The average Harris hip score (HHS) was improved from 58.0 preoperatively to 87.2 postoperatively. The average degree of cup abduction at the final follow up was 44.29. The centre of rotation of the hip joint was corrected from average 38.90mm (range: 22.15mm to 66.35mm) above the inter-teardrop line preoperatively to average 23.85mm (range: 11.82mm to 37.69mm) above the inter-teardrop line postoperatively. Out of 28 patients, 18 patients had three or more signs of osseointegration, according to the criteria of Moore, at the time of final follow up. Rest of patients, had one or two signs of osseointegration (5 patients had one sign and 5 patients had two signs). We had no patient with migration or loosening of acetabular components. No patient has osteolysis of acetabulum in any zone. Trabecular metal augments provide good initial stability to acetabular cup as well as helpful to bring down the centre of rotation of the hip joint within limit of 35mm above the inter-teardrop line. They also facilitate osseointegration. Our study showed that the results of the trabecular metal augments in reconstruction of acetabular bony defects were successful even in short term. However, long term study is required for better evaluation

A novel injectable hydrogel based on DNA and silicate nanodisks was fabricated and optimized to obtain a suitable drug delivery platform for biomedical applications. Precisely, the hydrogel was designed by combining two different type of networks: a first network (type A) made of interconnections between neighboring DNA strands and a second one (type B) consisting of electrostatic interactions between the silicate nanodisks and the DNA backbone. The silicate nanodisks were introduced to increase the viscosity of the DNA physical hydrogel and improve their shear-thinning properties. Additionally, the silicate nanodisks were selected to modulate the release capability of the designed network. DNA 4% solutions were heated at 90°C for 45 seconds and cooled down at 37°C degree for two hours. In the second step, the silicate nanodisks suspension in water at different concentrations (0.1 up to 0.5%) were then mixed with the pre-gel DNA hydrogels to obtain the nanocomposite hydrogels. Rheological studies were carried out to investigate the shear thinning properties of the hydrogels. Additionally, the hydrogels were characterized by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron microscopy. The hydrogels were loaded with the osteoinductive drug dexamethasone and its release was tested in vitro in phosphate buffer pH 7.4. The drug activity upon release was tested evaluating the osteogenic differentiation of human adipose derived stem cells (hASCs) in vitro through analysis of main osteogenic markers and quantification of alkaline phosphatase activity and calcium deposition. Finally, the hydrogels were tested in vivo and injected into cranial defects in rats to assess their biocompatibility and bone regeneration potential. The inclusion of the silicate nanodisks increased the viscosity of the hydrogels and the best results were obtained with the highest concentration of the nanoclay (0.5%). The hydrogels possessed shear-thinning properties as demonstrated by cyclic strain sweep tests and were able to recover their original storage modulus G' upon removal of strain. Such improvement in the injectable properties of the formulated hydrogels was mainly attributed to the formation of electrostatic interactions between the silicate nanodisks and the phosphate groups of the DNA backbone as confirmed by XPS analysis of the O, N, and P spectra. Additionally, laponite was able to sustain the release of the osteoinductive drug dexamethasone which was instead completely released from the DNA-based hydrogels after a week. The drug after being released was still active and promoted the osteogenic differentiation of hASCs as confirmed by ALP expression and expression of main osteogenic markers including ALP and COLA1. Finally, the gels proved to be biocompatible in vivo when injected into cranial defects and promoted bone formation at the periphery of the defect after a month post-treatment. A novel injectable shear-thinning DNA-based hydrogel was characterized and tested for its drug delivery properties. The hydrogel can promote the sustain release of a small molecule like dexamethasone and be biocompatible in vitro and in vivo. Due to these promising findings, the designed system could find also applicability for the delivery of growth factors or other therapeutic molecules

Revision surgery and surgery in previously operated areas are associated with an increased infection risk. In such situations, aggressive surgical debridement may be necessary to control and eradicate the infection. Full thickness defects resulting from such debridement present as a challenge. In most cases, an association of various methods, both surgical and non-surgical, is necessary. Our goal is to describe the use of vaccum dressings as an effective way to deal with extensive and infected dorsolumbar surgical defects, while avoiding the use of myocutaneous flaps. This is a retrospective and descriptive case report based on data from clinical records, patient observation and analysis of complementary exams. We present the case of a 57-years-old obese woman with prior history of double approach with posterior instrumentation and spine arthrodesis (D3 to L4) due to severe dorsolumbar adolescent idiopathic scoliosis. She presented to our consult 42 years after surgery, complaining of lower back pain. Clinical observation and imaging exams demonstrated degenerative disc disease in L5-S1 and L5 anterolisthesis. There was also distal instrumentation breakage (right L4 pedicular screw and contralateral rod) with pseudarthrosis suspicion. Distal instrumentation was removed and no pseudarthrosis was found. Therefore, posterior instrumentation and arthrodesis was performed, from L4 to S1. Surgery went without complications. One week after surgery, patient developed fever and inflammatory signs at the surgical incision, with purulent oozing. Escherichia coli and Proteus mirabilis were identified as the causative agents. Decision was made to remove both lumbar and distal dorsal instrumentation and perform aggressive debridement and lavage, with debridement surgery being repeated twice. Finally, a full thickness defect with approximately 20cm long and 6cm wide resulted from the debridement. A vacuum dressing was then applied, for 5 weeks, with progressive decrease in clinical and analytical inflammatory parameters and wound closure. Four months after the initial surgery, patient was discharged with complete defect closure and reepithelialization. This dressing technique provided a sound solution for defect resolution, as well as an important aid for infection control. It proved to be a viable option in an extensive defect, when surgical flap techniques and traditional dressing techniques could not provide a complete solution

This article is based on the analysis of surgical treatment peculiarities of 641 patients with post-osteomyelitis long bones defects. The average age of patients at the time of hospital admission was 32,4 ± 0,7 and ranged from 4 to 70 years. Most of them were people of active working age (476 (74.3%)) and male (523 (81.1%)). In this observation group 566 (88.3%) patients had the osteomyelitis process of the traumatic origin, including post-surgical (n = 155) and post-gunshot injuries (n = 13). Chronic hematogenous osteomyelitis was diagnosed in 75 (11.7%) patients. Most patients had lower extremity bones problems, including 444 tibia defects and 142 femoral bone defects. Much fewer patients had the osteomyelitis process of the upper extremity (humerus, radius, ulnar bone – 18, 19 and 18 respectively). Purulent necrotic process was accompanied by nonunion bone fragments in 160 (24%) patients, delayed union in 95 (14.6%) patients, false joint in 178 (27.6%) patients, segmental bone defect in 75 (11 5%) patients and bones union with edge defects and cavities in 143 (22.3%) patients. 340 (53%) patients were operated using the method of free bone grafting, and 301 (47%) patients were operated using the distraction method. The need to use the bilocal for external fixation on upper extremities occurs quite seldom (twice in our observations). Even when there is an upper extremity bone defect of several centimeters the preference should be given not to bilocal external fixation. When treating the lower extremities taking the above mentioned into consideration, segmental defects predominated, that is why the bilocal distraction-compression method of surgical treatment prevailed (98.6%). Thus, the main method of upper extremities long bones defects replacement is free bone grafting with segment fixation by the external fixation device, for lower extremities the is not-free main Ilizarov method, which allows to get positive results in 84.6% of patients with femoral bone problems and in 96.4% of tibia problems, mainly due to one-step treatment, directed simultaneously to inflammatory process elimination and maximum possible anatomical and functional restoration of the affected extremity

Introduction. The bone defect reconstruction is the first step of successful primary or revision TKA in case of large bone defect. If the defect is not reconstructed adequately, we can neither preserve knee joint function nor guarantee long survival of the implant. Allogeneic bone graft is known to be the treatment of choice in large defect. However the surgical technique is demanding and incorporation failure is constant issue of the allogeneic bone graft. We propose new bone defect reconstruction technique using multiple screws and cement. Material and method. From April 2012 to April 2014, 12 patients with large defect which could not be reconstructed with metal augment were involved in this study. The bone defect type was 10 cases of 2A and 2 cases of 2B according to AORI (Anderson Orthopedic Research Institute) classification. The defect was reconstructed with multiple screws and cementing technique by single surgeon (WS Cho). Average follow-up period was 15 months. (24 ∼ 1 month). Result. We analyzed 6 patients whose follow-up periods were more than 12 months. Average ROM was 107' and clinical scores were 86 by HSS, 93 by KS and 11 by WOMAC respectively. No complications such as infection and loosening were developed. Mean surgical time was 1 hour and 57 minutes. Conclusion. In short term follow-up, cementing technique using multiple screws can be a solution for large bone defect reconstruction