Tibial Defects Research Articles

Management of Segmental Tibial Bone Defects With the Magnetic Motorized Intramedullary Transport Nail: A Case Series.

Critical-sized bone defects in the tibia can arise as sequelae of trauma, infection, tumor, or the treatment of congenital limb deficiencies. Treatment of these defects often requires bone transport, which has traditionally been accomplished using circular external fixators. The development of a bone transport nail facilitated tibia reconstruction through distraction osteogenesis using an all-internal device, thus avoiding the complications associated with chronic external fixation. Given the rarity of these cases, few studies have been published on the reconstruction outcomes using this implant. We sought to investigate the bone healing indices (including regenerate consolidation and time to docking site union) associated with the use of a magnetically controlled all-internal bone transport nail for the reconstruction of 4 patients treated for posttraumatic tibial bone loss. Perioperative and device-related complications are also reported.

Development of novel waxy bone hemostatic agents composed of biodegradable polymers with osteogenic-enhancing peptides in rabbit models.

The use of bone wax is controversial for sternal hemostasis because it increases the risk of wound infection and inhibits bone healing. We developed new waxy bone hemostatic agents made from biodegradable polymers containing peptides, and evaluated them using rabbit models. We designed two types of waxy bone hemostatic agents: peptide wax and non-peptide wax, which used poly(ε-caprolactone)-based biodegradable polymers with or without an osteogenesis-enhancing peptide, respectively. Rabbits were randomly divided into four groups based on treatment with bone wax, non-peptide wax, peptide wax, or no treatment. In a tibial defect model, the bleeding amount was measured and bone healing was evaluated by micro computed tomography over 16 weeks. Bone healing in a median sternotomy model was assessed for 2 weeks using X-ray, micro computed tomography, histological examination, and flexural strength testing. The textures of peptide and non-peptide wax (n = 12 each) were similar to that of bone wax, and achieved a comparable degree of hemostasis. The crevice area of the sternal fracture line in the bone wax group was significantly larger than that in other groups (n = 10 each). The peptide wax group demonstrated the strongest sternal flexural strength (n = 10), with complete tibial healing at 16 weeks. No groups exhibited wound infection, including osteomyelitis. Waxy biodegradable hemostatic agents showed satisfactory results in hemostasis and bone healing in rabbit models, and may be an effective alternative to bone wax.

Achieving Correct Balance in Total Knee Arthroplasty with Fixed Varus Deformity.

Varus knee deformity is one of the most common deformities presenting for total knee arthroplasty (TKA). When present, a varus knee deformity contributes to overload of the medial joint compartment during gait, leading to increased medial compartment forces as well as lateral soft tissue lengthening. Additionally, a fixed varus deformity is associated with medial soft tissue contractures of the deep and superficial medial collateral ligament (MCL) and posteromedial capsule. With a fixed varus deformity, soft tissue releases may be necessary to create equivalent and rectangular flexion and extension gaps. There may also be anteromedial tibial bone defects, medial femoral condyle defects, and occasionally flexion contractures, especially in more severe cases. In cases of severe varus deformity with medial tibial bone loss, bone defects must be addressed to ensure adequate implant support. In many cases, a primary knee implant can be utilized in cases of varus knee deformity, but occasionally prostheses with higher levels of constraint may be required to balance and stabilize the knee. TKA has had a successful track record, with high levels of long-term implant survivorship even in cases of severe varus. Iatrogenic MCL instability and tibial aseptic loosening are complications associated with TKA in cases of severe varus, and multiple methods to avoid complications are presented here.

Adjustable bone plate: from bench to operating room.

We have designed an adjustable bone plate (ABP) which allows bone shortening and lengthening after fixation, which is a property not present in any of the plate systems available today. The aim of the current study was to examine the new ABP's segmental bone transfer capability for the treatment of a segmental bone defect in an animal model. Five sheep had ABPs attached to 10 of their tibias and bone defects of 15 mm in size were created. The pinion mechanism was moved with a manual screwdriver at a rate of 1mm/day for 15 days starting 3 days postoperatively. The animals were euthanized 3 months postoperatively, and the defect site and the transferred segment were evaluated by radiological and histological examination. The radiological results revealed successful transfers of 14.6 ± 1.2 mm of bone segment on all tibia defects without any complications. The histological evaluation showed new bone formation in both the extension and the docking sites. No rupture or breakage was observed within the plates. We have presented the potential of a new generation ABP for use in segmental bone transfer in an animal model as well as for future clinical applications.

Cleaved SPP1-rich extracellular vesicles from osteoclasts promote bone regeneration via TGFβ1/SMAD3 signaling

Bone remodeling is a tightly coupled process between bone forming osteoblasts (OBs) and bone resorbing osteoclasts (OCs) to maintain bone architecture and systemic mineral homeostasis throughout life. However, the mechanisms responsible for the coupling between OCs and OBs have not been fully elucidated. Herein, we first validate that secreted extracellular vesicles by osteoclasts (OC-EVs) promote osteogenic differentiation of mesenchymal stem cells (MSCs) and further demonstrate the efficacy of osteoclasts and their secreted EVs in treating tibial bone defects. Furthermore, we show that OC-EVs contain several osteogenesis-promoting proteins as cargo. By employing proteomic and functional analysis, we reveal that mature osteoclasts secrete thrombin cleaved phosphoprotein 1 (SPP1) through extracellular vesicles which triggers MSCs osteogenic differentiation into OBs by activating Transforming Growth Factor β1 (TGFβ1) and Smad family member 3 (SMAD3) signaling. In conclusion, our findings prove an important role of SPP1, present as cargo in OC-derived EVs, in signaling to MSCs and driving their differentiation into OBs. This biological mechanism implies a paradigm shift regarding the role of osteoclasts and their signaling toward the treatment of skeletal disorders which require bone formation.

Using novel porous metal pillars for tibial bone defects in primary total knee arthroplasty

BackgroundThe optimal method to treat tibial bone defects during primary total knee arthroplasty (TKA) is still unclear. A novel technique of porous metal pillar augmentation has been applied recently. This study aimed to assess the short-term outcomes of primary TKA with the use of novel porous metal pillars for tibial bone defects.MethodsA total of 24 cases (22 patients) of primary TKA between January 2019 and December 2020 using porous metal pillars for tibial bone defects were reviewed. Clinical results were evaluated using the Knee Society knee score (KSKS) and function score (KSFS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and range of motion (ROM). Hip-knee-ankle angle (HKAA), femorotibial angle (FTA), and radiolucent lines were assessed radiologically.ResultsThe median follow-up period was 36.0 months (interquartile range: 31–37 months). The KSKS, KSFS, WOMAC score, and ROM improved significantly at the final follow-up assessment compared with the preoperative evaluation. Both of the HKAA and FTA were corrected after surgery. Only one knee had a nonprogressive radiolucent line at the bone-cement interface. No radiolucent lines were detected around the pillar in any of the cases. There were no cases of prosthesis loosening and revision.ConclusionsThe use of novel porous metal pillars yielded satisfactory clinical outcomes and reliable radiological evidence of fixation in this study with a minimum 2-year follow-up. Porous metal pillar augmentation can be considered as a valuable and easy-to-use method for the management of tibial bone defects in primary TKA.

Machine learning-based design for additive manufacturing in biomedical engineering

While ceramic additive manufacturing (AM) technologies have shown great promise to create functional scaffolds with tailored biomechanical properties, the true potential of these advanced techniques has not been fully exploited yet due to lack of practical design optimisation approaches. To address this challenge, a machine learning (ML)-based design approach is proposed herein where ceramic 3D printing techniques are combined to fabricate functionally graded tissue scaffolds composed of Triply Periodic Minimal Surfaces (TPMS), aiming to fulfil the anticipated biomechanical requirements for the target bone regeneration outcomes. The proposed ML based design strategy couples a Bayesian optimisation (BO) algorithm to enable time-dependent mechano-biological optimisation of the 3D printed ceramic scaffolds at a reasonably low computational cost. For a representative example relating to bone scaffolding in a segmental defect of sheep tibia, the simulated results demonstrate that the optimised functionally graded scaffolds significantly enhance bone ingrowth outcomes. Furthermore, a Lithography-based Ceramic Manufacturing (LCM) technique is employed to fabricate the optimised scaffolds based on the proposed ML-based design framework, followed by micro-CT analyses of the additively manufactured ceramic scaffolds to assess their geometric qualities. This study is expected to gain new insights into mechanical sciences on design for varying material conditions and provide an effective design tool for ceramic additive manufacturing.

Histological and Immunohistochemical Characterization of Osteoimmunological Processes in Scaffold-Guided Bone Regeneration in an Ovine Large Segmental Defect Model.

Large-volume bone defect regeneration is complex and demands time to complete. Several regeneration phases with unique characteristics, including immune responses, follow, overlap, and interdepend on each other and, if successful, lead to the regeneration of the organ bone's form and function. However, during traumatic, infectious, or neoplastic clinical cases, the intrinsic bone regeneration capacity may exceed, and surgical intervention is indicated. Scaffold-guided bone regeneration (SGBR) has recently shown efficacy in preclinical and clinical studies. To investigate different SGBR strategies over periods of up to three years, we have established a well-characterized ovine large segmental tibial bone defect model, for which we have developed and optimized immunohistochemistry (IHC) protocols. We present an overview of the immunohistochemical characterization of different experimental groups, in which all ovine segmental defects were treated with a bone grafting technique combined with an additively manufactured medical-grade polycaprolactone/tricalcium phosphate (mPCL-TCP) scaffold. The qualitative dataset was based on osteoimmunological findings gained from IHC analyses of over 350 sheep surgeries over the past two decades. Our systematic and standardized IHC protocols enabled us to gain further insight into the complex and long-drawn-out bone regeneration processes, which ultimately proved to be a critical element for successful translational research.

Osseointegration enhancement by controlling dispersion state of carbonate apatite in polylactic acid implant

Osteoconductive ceramics (OCs) are often used to endow polylactic acid (PLA) with osseointegration ability. Conventionally, OC powder is dispersed in PLA. However, considering cell attachment to the implant, OCs may be more favorable when they exist in the form of aggregations, such as granules, and are larger than the cells rather than being dispersed like a powder. In this study, to clarify the effects of the dispersion state of OCs on the osseointegration ability, carbonate apatite (CAp), a bone mineral analog that is osteoconductive and bioresorbable, powder–PLA (P-PLA), and CAp granule–PLA (G-PLA) composite implants were fabricated via thermal pressing. The powder and granule sizes of CAp were approximately 1 and 300–600 µm, respectively. G-PLA exhibited a higher water wettability and released calcium and phosphate ions faster than P-PLA. When cylindrical G-PLA, P-PLA, and PLA were implanted in rabbit tibial bone defects, G-PLA promoted bone maturation compared to P-PLA and pure PLA. Furthermore, G-PLA bonded directly to the host bone, whereas P-PLA bonded across the osteoid layers. Consequently, the bone-to-implant contact of G-PLA was 1.8- and 5.6-fold higher than those of P-PLA and PLA, respectively. Furthermore, the adhesive shear strength of G-PLA was 1.9- and 3.0-fold higher than those of P-PLA and PLA, respectively. Thus, G-PLA achieved earlier and stronger osseointegration than P-PLA or PLA. The findings of this study highlight the significance of the state of dispersion of OCs in implants as a novel strategy for material development.

Excellent mid- to long-term survival of tantalum metal cones in a case series of revision knee arthroplasty with severe bony defects

PurposeSevere metaphyseal bone defects remain a challenge and represent a growing problem in revision total knee arthroplasty (RTKA). The purpose of this study was to examine the survival of first-generation tantalum metal cones (TMC) and to assess clinical and radiographic data obtained from mid- to long-term follow-ups (FU) after RTKA with severe bony defects.MethodsThis retrospective case series included 100 consecutive patients of the same centre, who underwent RTKA surgery with TMC for tibia and/or femur bone defects between January 2011 and December 2015. Fourteen patients had died and six were lost for FU, leaving a total of eighty patients (one hundred and twelve TMC) for final evaluation. Clinical parameters including the Knee Society Score (KSS), visual analogue scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and range of motion (ROM) were determined preoperatively based on the patients’ medical charts, and assessed again during the final FU after an average of 6.1 (5–9) years postoperative. Standardised postoperative X-rays were analysed during the final FU visit for osseointegration of the cones, and any signs of implant loosening were assessed with the modified Knee Society Radiographic review criteria. Perioperative and postoperative complications, reoperations, as well as implant and cone re-revisions were analysed. Survivorship analysis was performed with (a) cone-related revision for any reason and (b) implant component revision for any reason.ResultsPrevious RTKA had to be performed due to 64 (80%) aseptic and 16 (20%) septic failures. At the final FU, 75 (94%) tibia and 76 (95%) femur TMCs and implants were clinically stable. One patient experienced loosening of cones and implants at the femur and tibia but denied re-revision surgery. There were eight (10%) reoperations including two early wound healing problems, two inlay changes, two periprosthetic fractures, one debridement, antibiotics and implant retention (DAIR), and one secondary patella replacement. The six (7.5%) re-revisions included two aseptic loosening’s of the opposite implant without TMC, one arthrodesis for recurrent instability, and three deep infections managed by two two-stage exchanges, and one amputation for persistent infection. At re-revision, all TMC cones were osteointegrated without signs of loosening. The determined clinical parameters showed significant (p < 0.001) postoperative improvement, and objective KSS was rated as excellent in 51%, and as good in 22% of patients at the final FU. The estimated 8-year Kaplan–Meier survival was 95% for TMC and 92.5% for implant components.ConclusionTantalum metal cones (TMC) demonstrate a secure fixation for treatment of severe femoral and tibial metaphyseal bone defects during RTKA. This fixation concept showed excellent mid- to long-term clinical and radiographic outcomes with promising 8-year survival rates for cones and implant components.Level of evidenceRetrospective cohort study, Level IV.

Resorbable Layered Double Hydroxides‐Based Composite Implants Synergistically Accelerates Critical‐Sized Defect Closure

AbstractThe study focuses on the fabrication of a composite implant composed of MgAl layered double hydroxides (LDH), gelatin, and diosgenin and its regeneration potential in experimentally‐induced tibial defect in rabbits. The implant is fabricated by blending and lyophilization technique and eventually cross‐linked using glutaraldehyde. The implant is characterized by attenuated total reflectance (ATR) spectroscopy, scanning electron microscopy (SEM), atomic force microscopy (AFM), and compressive strength. A sustained release of diosgenin occurs over a period of 28 days. The osteogenic activity is analyzed by alkaline phosphatase activity and alizarin red S staining; that aid in determining the extent of biomineralization. The results also demonstrate that LGD100 implant stimulates the expression of genes associated with osteoblastic activities in MG‐63 cells, namely type I collagen, osteocalcin, and osteopontin. The bone regeneration capacity of diosgenin‐loaded gelatin‐based LDH implant is then tested by creating critical bone defects in the tibia of rabbits by using empty bone defects as controls. Periodic radiographs are taken which show promising results. Histological and immunohistochemical staining confirm that after treatment with LGD100, new bone is formed at the defect site. This study suggests that LGD100 implant aids in faster bone formation as it mimics the natural properties of bone.

Efficacy and Versatility of the Medial Hemisoleus Flap for Complex Middle Third Tibial Defects: A Presentation of 2 Cases

Soft tissue injuries involving the middle third of the tibia can present significant clinical challenges, often leading to complications such as infection and nonunion. This article explores the efficacy of the medial hemisoleus flap as a valuable surgical technique for addressing these complex wounds. Two case reports are presented to illustrate the successful use of this flap in clinical practice. The medial hemisoleus flap offers consistent blood supply, improved arc of rotation, and reduced donor site morbidity, making it an excellent choice for reconstructive surgery in this anatomical region. In the first case, a 17-year-old patient with a history of smoking developed an open fracture in his left leg two years after a car accident, which led to a soft tissue defect with exposed bone in the middle third of his left leg. In the second case, a 25-year-old male involved in a traffic accident presented with a displaced open bone fracture of the middle third of the tibia and fibula with bone sequestrum. Surgical technique, advantages, patient selection criteria, and outcomes are discussed, highlighting the significance of the medial hemisoleus flap in addressing these challenging wounds.

Distally Based Pedicled Fibula Flap for Reconstruction of Distal Tibia After Oncological Resection: A Case Series and Review of Literature.

Reconstruction of distal tibial defects pose a difficult challenge because the bone is subcutaneous and close to the tendons and neurovascular bundles. Distally based pedicled fibula with retrograde flow can be used for the reconstruction of distal tibial defects. This is based on the communicating branch of the peroneal artery to the posterior tibial artery. We present three cases of distal tibia primary tumours which were resected and reconstructed using recycled autograft plus distally based pedicled fibula and ankle arthrodesis. This pedicled retrograde fibula flap is a novel technique for the reconstruction of distal tibial defects after oncological resections. It provides a vascularized graft without the need for microvascular surgery and without violating the normal limb. Meticulous dissection of and preservation of the communicating branches between the peroneal artery and the posterior tibial artery with confirmation of retrograde flow before dividing the proximal peroneal pedicle is sine quo non for the success of this graft. This flap overcomes the drawback of the limited arc of rotation and limited reach of proximal pedicle-based flap for distal tibial reconstruction. Long-term functional outcomes, limb shortening associated with this flap, and its effect on functional outcomes remain to be ascertained.

Delayed Reconstruction of the Perforator Pedicle Propeller Flap after the Induced Membrane Technique for Gustilo IIIB Open Distal Tibial Fracture.

This study aimed to evaluate the safety and efficacy of delayed reconstruction of the perforator pedicle propeller flap after the induced membrane technique in the treatment of Gustilo IIIB open distal tibial fracture, and to evaluate the clinical outcome and complications of two different perforator pedicle propeller flaps.Thirty-four patients with Gustilo IIIB open distal tibial fractures treated by the induced membrane technique and delayed reconstruction of two different perforator pedicle propeller flaps from May 2017 to March 2022 were retrospectively analyzed. Patients were divided into two groups according to the different kinds of perforator pedicle propeller flaps covered. The operation required two stages. The Radiographic Union Score for Tibial fractures (RUST) was used to evaluate the healing of the tibial bone defect. The American Orthopaedic Foot and Ankle Society (AOFAS) score was used to evaluate ankle function. The complications associated with the technique were recorded.The number of serial debridements, excluding those performed during emergency and final operations, was a mean of 2.28±0.83 in the PAPF group. The PAPF group had a mean bone defect length of 6.76 ± 0.69 cm, the median healing time of 13.11 ± 0.96 months, RUST score 12.68 ± 1.63, and AOFAS score of 84.12 ± 6.38. On the other hand the PTAPF group's mean bone defect length was 6.73 ± 0.95 cm, the median healing time 12.63 ± 1.46 months, RUST score 13.73 ± 1.53 and AOFAS score 82.79 ± 5.49. There were no observed significant differences the two groups in the number of serial debridements, bone defect length, bone union time, RUST score, or AOFAS score (p>0.05). Flap size ranged from 9×6cm2 to 14×7cm2 in the PAPF group and from 9×6cm2 to 13×7cm2 in the PTAPF group. There were no severe complications such as flap-related complications or amputation. The differences in complications in the two groups were not statistically significant.In cases of severe open tibial fracture, the reconstructive method is important. When delayed reconstruction is inevitable, surgeons should first perform radical debridement, followed by vacuum sealing drainage as a bridging therapy; both PAPF and PTAPF can be considered for definitive soft tissue coverage.

Bone Marrow Stromal Cells Sorted by Semiconducting Polymer Nanodots for Bone Repair.

The use of bone marrow stromal cells (BMSCs) for bone defect repair has shown great promise due to their differentiation potential. However, isolating the BMSCs from various cell types within the bone marrow remains challenging. To tackle this issue, we utilized semiconducting polymer dots (Pdots) as markers to select the BMSCs within a specific time frame. The therapeutic efficacy of the obtained Pdot-labeled BMSCs was assessed in a bone defect model. Initially, we evaluated the binding capacity of the Pdots with four different types of cells present in the bone marrow including BMSCs, osteoblasts, macrophages, and vascular endothelial cells, in vitro. Notably, BMSCs showed the most rapid uptake of the Pdots, being labeled within only one h of coculture, while other cells took four h to become labeled. Moreover, by colocalizing the Pdots with Prrx1, Sca-1, OSX, F480, and CD105 in the bone marrow cells of monocortical tibial defect (MTD) mice in vivo, we determined the proportions of BMSCs, macrophages, and vascular endothelial cells among all labeled cells from 1 to 8 h after the Pdots injection. It was found that BMSCs have the highest proportion (92%) among all labeled cells extracted after 1 h of Pdots injection. The therapeutic efficacy of the obtained Pdots-labeled BMSCs (1 h) was assessed in a bone defect model. Results showed that the new bone accrual was significantly increased in the treatment of Pdots-labeled BMSCs compared to the bone marrow cell-treated group. Our study revealed that BMSCs screened by the Pdots could improve bone defect repair, suggesting a promising application of the Pdots in bone healing.

Stability of Three-Dimensional Printed Custom-Made Metaphyseal Cone for Tibial Bone Defects Reconstruction: A Finite Element Analysis and Biomechanical Study.

The reconstruction of bone defects in tibial revision knee arthroplasty is challenging. In this study, we evaluated the primary stability of a novel three-dimensional (3D)-printed custom-made metaphyseal cone for Anderson Orthopedic Research Institute (AORI) IIb or III bone defect reconstruction in tibial revision knee arthroplasty using the combination of finite-element analysis and biomechanical experiments. In the finite-element analysis, AORI II b and III medial tibial bone defects were designed at varying depths. A novel 3D-printed custom-made metaphyseal cone was designed and used to reconstruct the bone defect with or without a stem in simulated revision total knee arthroplasty (RTKA). A no-stem group and a stem group were established (based on whether a stem was used or not). Von Mises stress and micromotion were calculated with varying depths of bone defects, ranging from 5 mm to 35 mm, and then micromotions at the bone-implant interface were calculated and compared with the critical value of 150 μm. In the biomechanical experiment, the no-stem group was used, and the same bone defects were made in four synthetic tibias using patient-specific instruments. Micromotions at the bone-implant interface were investigated using a non-contact optical digital image correlation system and compared with the critical value of 150 μm. When the bone defect was <30 mm, micromotions at the bone-implant interface in the finite-element analysis were all below 150 μm both in the stem groups and no-stem groups, whereas those in the biomechanical experiment were also below 150 μm in the no-stem group. The 3D-printed custom-made metaphyseal cone in RTKA has excellent primary stability and does not require stems in reconstructing tibial AORI type IIb or III bone defects with a depth of <30 mm.

The polymicrobial infection affects the infection recurrence rate (not failure) in treating femoral and tibial bone defects with the Masquelet technique-a comparative retrospective analysis of 54 patients with mono- and polymicrobial infections.

This study evaluated whether polymicrobial infection affects reoperation rates due to infection recurrence and treatment failure with the Masquelet technique in infected posttraumatic segmental bone defects of the femur and tibia. We retrospectively analyzed patients treated between 2012 and 2021 in two trauma referral centers. We evaluated demographic data, injury, treatment, infection recurrence, failures, and bone healing rates according to whether the infection was mono- or polymicrobial. After uni-bivariate analysis between patients with polymicrobial and monomicrobial infection, we identified the variables associated with infection recurrence and failure through multivariate analysis. We analyzed 54 patients, 30 (55.55%) with tibial and 24 (44.44%) femoral segmental bone defects, with a mean follow-up of 41.7 ± 15.0months. Forty-four (81.48%) presented monomicrobial, and 10 (18.51%) polymicrobial infections. Comparatively, the need for soft tissue reconstruction and the infection recurrence rate was significantly higher in patients with polymicrobial infections. There was no significant difference in the failure rate (20 vs. 6.81% p = 0.23). Multivariable logistic regression analysis identified the polymicrobial infection as the only independent variable associated with infection recurrence (Odds Ratio = 11.07; p = 0.0017). Our analysis suggests that polymicrobial infection is associated with a higher risk of infection recurrence in treating the femur and tibia segmental bone defects with the Masquelet technique. This information can help surgeons to inform patients about this and give them a realistic expectation of the outcome and the possibility of reoperation.

Tuberous sclerosis complex 1 targeted depletion in macrophages promotes osteogenesis by modulating secretion of Oncostatin M in the inflammatory stage of bone healing

In bone healing, earlier bone formation benefits bone repair. The first process of repair following bone injury involves the interaction between macrophage polarization and osteogenic activation of osteoblast linage cells, but the radical difference between the contributions of classically-activated M1 macrophages and alternatively-activated M2 macrophages to osteogenesis remains obscure. To test our hypothesis that M1 macrophages promote bone healing, we generated transgenic mice with myeloid lineage-specific TSC1 deletion (TSC1KO) to investigate the functional roles of M1 macrophages in the process of bone defect healing. We demonstrated that constitutive activation of mammalian target of rapamycin complex 1 (mTORC1) enhances M1 macrophage polarization during bone healing. By creating tibial bone defect as a model of bone repair in TSC1KO mice and their littermates, we surprisingly found osteogenic responses in the defective bone region of TSC1KO mice, where repair occurred by intramembranous ossification (IO) in the mice was promoted due to the enhanced M1-polarized macrophage polarization. We propose that Oncostatin M (OSM) secreted by M1-polarized macrophages but not M2 macrophages likely functions as a paracrine factor in this promoted repair process, as verified by the induction of osteoblastic differentiation and matrix mineralization. Interestingly, the expression level of the OSM receptor (OSMR) was continually upregulated in osteoblast linage cells with M1 medium. Additionally, OSMR activated the signaling transduction system of JAK/STAT/RUNX2 in MSCs, which in turn stimulates the recruitment of osteoblast lineage cells and activates IO. These results indicate that TSC1 targeted depletion in macrophages promotes bone healing by inducing secretion of OSM. This study highlights that regulation of M1 macrophage polarization is a novel basis for the improvement of bone regeneration and that regulation of macrophage polarization can be a potential therapeutic strategy to treat defects in the repair phase of bone healing.

Management of composite tibial and soft tissue defects via intramedullary bone transport devices and microvascular free flaps: A treatment algorithm and presentation of two cases

Management of composite tibial and soft tissue defects via intramedullary bone transport devices and microvascular free flaps: A treatment algorithm and presentation of two cases

Reconstruction of a Severe Open Tibiofibular Fracture using an Ipsilateral Vascularized Fractured Fibula with a Thoracodorsal Artery Perforator Free Flap.

The Gustilo IIIB tibiofibular fractures often result in long bone loss and extensive soft tissue defects. Reconstruction of these complex wounds is very challenging, especially when it includes long bone grafts, because the donor site is limited. We describe our experience using a set of chimeric ipsilateral vascularized fibula grafts with a thoracodorsal artery perforator free flap to reconstruct the traumatic tibia defects. A 66-year-old male suffered a severe comminuted tibia fracture and segmented fibula fracture with large soft tissue defects as a result of a traffic accident. He also had an open calcaneal fracture with soft tissue defects on the ipsilateral side. All the main vessels of the lower extremity were intact, and the cortical bone defect of the tibia was almost as large as the fractured fibula segment. We used an ipsilateral vascularized fibula graft to reconstruct the tibia and a thoracodorsal artery perforator flap to resurface the soft tissue, using the distal ends of peroneal vessels as named into sequential chimeric flaps. After 3 weeks, the calcaneal defect was reconstructed with second thoracodorsal artery perforator free flap. Reconstruction was successful and allowed rapid rehabilitation because of reduced donor site morbidity.