Axillary Artery Injury Associated with Dislocated or Displaced Proximal Humeral Fracture: A Report of 3 Cases.

CASE: (1) A 69-year-old man sustained a proximal humeral fracture-dislocation. During emergency surgery, copious bleeding occurred. A pseudoaneurysm was identified 30 days postoperatively. (2) A 69-year-old man sustained a proximal humeral fracture and axillary artery injury. Physical examination demonstrated a cold but pink hand. Hemiarthroplasty and bypass vein grafting were performed. (3) An 86-year-old woman sustained a proximal humeral fracture and axillary artery injury. Her hand had turned cold and pale. Reverse shoulder arthroplasty and bypass vein grafting were performed. CONCLUSION: In cases of proximal humeral fractures with significant displacement, concomitant axillary artery injury must be assessed and if there is a high index of suspicion, prompt advanced imaging is necessary.

Risk Factors for Reintubation After Anterior Cervical Spine Surgery: Comparative Study of Patients With Cervical Spine Trauma and Patients With Cervical Degenerative Disease.

STUDY DESIGN: Single-center retrospective study. OBJECTIVES: The aim was to compare the postoperative outcomes of anterior cervical spine surgery (ACSS) in patients with and without cervical spine trauma. SUMMARY OF BACKGROUND: Few papers have addressed airway obstruction after anterior ACSS for patients with cervical spine trauma. This study aimed to compare airway obstruction after ACSS between patients with cervical degenerative disorders and cervical spine injuries and identify the risk factors for unplanned postoperative reintubation. MATERIALS AND METHODS: Seventy-seven patients who underwent ACSS were enrolled in this retrospective study. There were 52 men and 25 women, with a mean age of 60.3±15.5 years old. The causes of surgery were as follows: 24 cervical spine fractures or dislocations, 12 spinal cord injuries without bony fracture, 19 disc herniations, and 22 myelopathies. The patients' characteristics, operative data, and risk factors for unplanned reintubation within 5 days postoperatively were analyzed using medical records. RESULTS: Postoperative reintubation was performed in 3 patients (3.9%), all of whom suffered trauma. We further examined risk factors for reintubation in patients in the trauma group. There was no significant difference between the reintubation (R) and nonreintubation (non-R) groups in age, sex, body mass index, amount of blood loss and operation time, preoperative paralysis severity, and the number of fused segments. Patients in group R had significantly higher rates of severe anterior element injury (100% vs. 27.3%, P=0.0011). Airway obstruction due to laryngopharyngeal edema and swelling was confirmed by laryngoscopy and computed tomography images. CONCLUSIONS: Unplanned reintubation after ACSS occurred at a higher rate in trauma patients than in patients with degenerative disorders. Our results suggested that the severe damage to the anterior element of the cervical spine was associated with postoperative reintubation. EVIDENCE LEVEL: Level IV.

Risk Factors for the Incidence of the Volar Lunate Facet Fragments in Distal Radius Fractures.

Background The volar lip of the distal radius is the key structure for wrist joint stability. Rigid fixation of the volar lunate facet (VLF) fragment is difficult because of its unique anatomy, and a high rate of postoperative displacement was demonstrated. Purposes The aim of the study is to identify risk factors for VLF in distal radius fractures (DRFs) and to reconsider the important point for primary fixation. Patients and Methods One hundred fifty-five patients who underwent open reduction and internal fixation for an DRF were included and classified into one of the following two groups: VLF(+)or VLF(-). Demographic data, including age, sex, body mass index (BMI), laterality, trauma mechanism, and AO Foundation/Orthopaedic Trauma Association (AO/OTA) classification were recorded. Several parameters were investigated using wrist radiographs of the uninjured side and computed tomography scans of the injured side. Univariate and multivariate logistic regression analyses were performed to evaluate the risk factors for VLF. Results There were 25 patients in the VLF(+) group and 130 patients in the VLF(-) group. The incidence of VLF was 16.1%. The VLF(+) group tended to have a higher BMI and higher energy trauma mechanism. The odds ratio for the sigmoid notch angle (SNA), volar tilt (VT), and lunate facet curvature radius (LFCR) were 0.84, 1.32, and 0.70, respectively, with multivariate analysis, which was significant. A smaller SNA, larger VT, and smaller LFCR are potential risk factors for VLF. Conclusion Over-reduction of the VT at primary fixation should be avoided because it could place an excess burden on the VLF and cause subsequent postoperative fixation failure and volar carpal subluxation. Level of Evidence IV.

Preoperative Lower-Limb Muscle Predictors for Gait Speed Improvement after Total Hip Arthroplasty for Patients with Osteoarthritis.

This study aimed to identify preoperative lower-limb muscle predictors for gait speed improvement after total hip arthroplasty (THA) with hip osteoarthritis. Gait speed improvement was evaluated as the subtraction of preoperative speed from postoperative speed. The preoperative muscle composition of ipsilateral hip abductors was evaluated using computed tomography. The females (n = 45) showed smaller total cross-sectional areas of the gluteal muscles than the males (n = 13). The gluteus maximus in the females showed lower lean muscle mass area (LMM) and higher ratios of the intramuscular fat area and the intramuscular adipose tissue area to the total muscle area (TM) than the males. Regression analysis revealed that LMM/TM of the glutei medius and minimus may correlate negatively with postoperative improvement in gait speed. Receiver operating characteristic curve analysis for prediction of minimum clinically important improvement in gait speed at ≥0.32 m/s resulted in the highest area under the curve for TM in the upper portion of the gluteus maximus with negative correlation. The explanatory variables of hip abductor muscle composition predicted gait speed improvement after THA more precisely in the females compared with the total group of both sexes. Preoperative muscle composition should be evaluated separately based on sex for the achievement of clinically important improvement in gait speed after THA.

Which head element is more effective for cement augmentation of TFNA? Helical blade versus lag screw.

BACKGROUND: Early fixation and rehabilitation is the gold standard treatment for intertrochanteric femur fractures. Cement augmentation through perforated head elements has been developed to avoid postoperative complications such as cut-out or cut-through. The purpose of this study was to compare two head elements in terms of cement distribution using computed tomography (CT) and to examine their initial fixation and clinical outcomes. METHODS: Elderly patients who had intertrochanteric fractures were treated with a trochanteric fixation nail advanced (TFNA) helical blade (Blade group) or a TFNA lag screw (Screw group). In both groups, 4.2 mL of cement was injected under an image intensifier (1.8 mL of cement was directed cranially and 0.8 mL each caudally, anteriorly, and posteriorly). Patient demographics and clinical outcome were investigated post-operatively. Cement distribution from the center of the head element was evaluated with CT. Maximum penetration depth (MPD) were measured in the coronal and sagittal planes. On each axial plane, the cross-sectional areas in the cranial, caudal, anterior and posterior directions were calculated. The sum of cross-sectional areas (successive 36 slices) was defined as the volume of the head element. RESULTS: The Blade group included 14 patients, and the Screw group included 15 patients. In the Blade group, MPD in the anterior and caudal direction was significantly greater than that in the posterior direction (p < 0.01). In the Screw group, volume in the cranial and posterior direction was significantly greater than that in the Blade group (p = 0.03). Subsequently, the total volume in the Screw group was significantly larger than that in the Blade group (p < 0.01). No significant correlation was detected between bone mineral density, T score, young adult mean, and total cement volume. Change in radiographic parameters and clinical outcome such as Parker score and visual analog scale were similar in both groups. No patients suffered from cut-out / cut through or non-union. CONCLUSIONS: The position of cement distribution through the lag screw is different from that through the helical blade, and the total volume of the head element is significantly larger in the lag screw. Both groups had similarly effective results in terms of mechanical stability after surgery, postoperative pain and early phase of rehabilitation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN45341843, 24/12/2022, Retrospectively registered.

Activation of STAT3 (signal transducer and activator of transcription 3) in synovial tissues from the hip joint in the early stage of rapidly destructive coxopathy.

Interleukin-6 signaling activates signal transducer and activator of transcription 3 (STAT3), resulting in matrix metalloproteinase-3 (MMP-3) production. The hip joints with rapidly destructive coxopathy (RDC) show rapid chondrolysis, probably by increased MMP-3. This study aimed to elucidate STAT3 activation in the synovial tissues with joint destruction in the early stage of RDC. Synovial tissues within 7 months from the disease onset were obtained from four RDC patients with femoral head destruction and high serum levels of MMP-3. RDC synovial tissues demonstrated the synovial lining hyperplasia with an increase of CD68-positive macrophages and CD3-positive T lymphocytes. STAT3 activation was found in the synovial tissues by immunohistochemistry using anti-phospho-STAT3 antibody. The majority of phospho-STAT3-positive cells were the synovial lining cells and exhibited negative expression of the macrophage or T cell marker. Treatment with CP690,550, a Janus Kinase inhibitor, resulted in a decrease in phospho-STAT3-positive cells, especially with high intensity, indicating effective suppression of STAT3 activation in RDC synovial tissues. Inhibitory effect of CP690,550 could work through the Janus Kinase/STAT3 axis in the synovial tissues in the early stage of RDC. Thus, STAT3 may be a potential therapeutic target for prevention of joint structural damage in RDC.

Minimally invasive transiliac anatomical locking plate for posterior pelvic ring injury: A technical trick of the gull wing plate.

Posterior pelvic ring injuries commonly involve sacral fractures, which are difficult to reduce and stabilize. Because conservative treatment requires long-term bedrest and leads to unsatisfactory outcomes, surgical intervention is a beneficial option to protect neurological structures and provide sufficient stability for early mobilization. Several studies have investigated a variety of internal fixation techniques, such as iliosacral screws, transiliac bars, spinal instruments, and transiliac plates. The gull wing plate (GWP) is a pre-contoured anatomical locking plate with two cancellous screws (φ6.5 mm) and four locking screws (φ5.0 mm), the design of which is unique among posterior tension-band plates. The GWP provides reliable stability of the posterior construct of the pelvic ring and accelerates rehabilitation. Compared to alternative surgical techniques for posterior fixation, the simple surgical procedure of the GWP is minimally invasive and highly reproducible, which leads to fewer complications and less radiation exposure.

Minimally invasive transiliac anatomical locking plate for posterior pelvic ring injury: a retrospective analysis of clinical outcomes and radiographic parameters for the gull wing plate.

BACKGROUND: Posterior pelvic ring injuries are challenging for surgeons to treat adequately due to difficulties with reduction and stabilization. Surgical intervention is a beneficial option to protect neurological structures and provide sufficient stability for early mobilization. The gull wing plate (GWP) is a pre-contoured anatomical locking plate with six screws, and its design is unique among posterior transiliac tension-band plates. The purpose of this study was to investigate clinical results of the GWP. METHODS: Patients who had an unstable posterior pelvic ring injury and underwent internal fixation with GWP were retrospectively analyzed at a trauma center. Demographic data, fracture type, perioperative data, and radiological evaluation with computed tomography (CT) were collected. Clinical outcomes were graded using the functional independence measure (FIM) and Majeed outcome score. RESULTS: Twenty-six patients were enrolled (mean age, 54 years), and the mean follow-up period was 23 months. The mean Injury Severity Score was 24 points, and internal fixation was performed 6.6 days post-trauma. CT evaluation showed the lateral surface angle of the uninjured ilium was approximately 68°. The GWP pre-contoured anatomical design closely matched this angle. The mean FIM and Majeed score were 119 and 76 points, respectively, which were graded as excellent (n = 14), good (n = 9), or fair (n = 3). CONCLUSIONS: With the retrospective single-center data available, the GWP seems to be a minimally-invasive alternative, provides reliable stability of the posterior pelvic ring and allows for rehabilitation within normal ranges.

Cement distribution and initial fixability of trochanteric fixation nail advanced (TFNA) helical blades.

INTRODUCTION: Early fixation and rehabilitation is the gold standard treatment for intertrochanteric femur fractures. To avoid postoperative complications such as cut-out or cut-through, cement augmentation with perforated helical blades has been developed. The purpose of this study was to evaluate the distribution of injected cement at the head-neck portion of proximal femur using computed tomography (CT) and to examine its initial fixability and clinical outcomes. PATIENTS AND METHODS: Elderly patients who had intertrochanteric fractures were treated with a helical blade only (BO group) or with a helical blade and cement augmentation (CA group). After fracture reduction, trochanteric fixation nail advanced (TFNA) helical blades were inserted, aiming at the center/center position with 20 mm of tip-apex distance. In the CA group, 4.2 mL of cement was injected under an image intensifier (1.8 mL of cement was directed cranially and 0.8 mL each was directed to the caudally, anteriorly, and posteriorly). Patient demographics, radiographic parameters with CT, and post-operative clinical outcome were examined. RESULTS: Each group included nine patients with similar demographics. Maximum penetration depth (MPD) in the CA group was significantly greater than those in the BO group for all four directions (p < 0.01). In the CA group, the anterior MPD was significantly greater than the posterior (p < 0.01) and the cranial (p = 0.02) MPD. Surface area and volume in the CA group were two-times and three-times larger than that in the BO group, respectively. Among radiographic parameters, ΔRotation angle in the CA group was significantly smaller than that of the BO group (p = 0.03). For the ΔParker score, the CA group showed less of a decrease than in the BO group (p < 0.01). Visual analog scale (VAS) for the passive range of motion (ROM) and for full-load walking in the CA group was significantly lower than those in the BO group (p < 0.01). CONCLUSIONS: The initial fixability of the TFNA helical blade with cement augmentation demonstrated double the surface area and triple the volume. This suppressed implant micro-motion, reduced postoperative pain, and accelerated rehabilitation in the acute phase.

Corticosteroid-associated osteonecrosis of the femoral head after orthotopic liver transplantation and the outcomes of subsequent total hip arthroplasty.

BACKGROUND: Corticosteroids are essential for immunosuppression after orthotopic liver transplantation (OLT), but also have many side effects. Osteonecrosis of the femoral head (ONFH) is one of the most serious complications requiring prostheses. However, few studies have investigated ONFH after OLT. The purpose of this study is to survey the incidence of corticosteroid-induced ONFH after OLT and the outcomes of total hip arthroplasty (THA). METHODS: Between January 2001 and December 2010, a series of 926 patients underwent OLT at our Hospital. A retrospective analysis was performed on a total of 738 patients who survived at least 2 years after OLT. The incidence of symptomatic ONFH, the interval from OLT to the initial diagnosis of ONFH, and the cumulative dose of corticosteroids were analyzed. The side effects related to OLT, such as other osteonecrosis lesions, osteoporotic fractures, and infection, were monitored. For patients who underwent THA, radiological findings and Japanese Orthopaedic Association (JOA) scores were evaluated. RESULTS: ONFH occurred in 10 patients (13 hips) (6 men [7 hips], 4 women [6 hips]), with an incidence of 1.36%. The average age at OLT was 51.4 years (range, 31-61 years). The average interval from OLT to ONFH was 86.7 months (range, 22-155 months). The average cumulative dose of corticosteroids was 7274 mg (range, 1342-29,514 mg). Twenty patients suffered from side effects related to OLT. Seven patients (8 hips) underwent THA. No adverse events including infection arose during the perioperative process. One hip dislocated, and one femoral stem displayed a radiolucent line. The average JOA score improved from 45.4 (range, 25-76) preoperatively to 86.9 (range, 73-99) at final follow-up. No patients required revision surgery. CONCLUSIONS: The incidence of symptomatic ONFH after OLT was 1.36%. Once the graft function becomes stable, THA can be a safe and effective treatment option for patients with ONFH after OLT.

Mechanism of Peripheral Nerve Regeneration Using a Bio 3D Conduit Derived from Normal Human Dermal Fibroblasts.

BACKGROUND: We previously reported the development of a scaffold-free Bio three-dimensional (3D) nerve conduit from normal human dermal fibroblasts (NHDFs). The aim of this study was to investigate the regenerative mechanism of peripheral nerve cells using a Bio 3D conduit in a rat sciatic nerve defect model. METHODS: Bio 3D conduits composed of NHDFs were developed, and cell viability was evaluated using a LIVE/DEAD cell viability assay immediately before transplantation and 1-week post-surgery. Tracking analysis using PKH26-labeled NHDFs was performed to assess the distribution of NHDFs within the regenerated nerve and the differentiation of NHDFs into functional Schwann cells (SCs). RESULTS: The assessment of the viability of cells within the Bio 3D conduit showed high cell viability both immediately before transplantation and 1-week post-surgery (88.56 ± 1.70 and 87.58 ± 9.11, respectively). A modified Masson's trichrome staining of the Bio 3D conduit revealed the formation of a prominent extracellular matrix (ECM) in between the cells. We observed, via tracking analysis, that the tube-like distribution of the NHDFs remained stable, the majority of the regenerated axons had penetrated this structure and PKH26-labeled cells were also positive for S-100. CONCLUSION: Abundant ECM formation resulted in a stable tube-like structure of the Bio 3D conduit with high cell viability. NHDFs in the Bio 3D conduit have the potential to differentiate into SCs-like cells.

Functional anatomy of the sagittal bands and mechanisms of extensor tendon dislocation: a cadaveric study.

We investigated the functional anatomy of the radial sagittal band and possible mechanisms involved in its spontaneous and traumatic rupture using seven cadaveric hands. First, the extensor tendon excursion and the change in angle between the sagittal bands and the tendon path were measured during metacarpophalangeal joint flexion. The radial bands were then divided in two different ways that mimicked spontaneous or traumatic rupture. We found no significant correlation between the extensor tendon excursion and the change in angle of the sagittal bands in the middle and ring fingers. Dislocation could occur when the radial sagittal band was only partially divided. This may explain why conservative treatment of tendon dislocation in the middle and ring fingers is feasible. Complete section of the sagittal bands in the little finger caused ulnar dislocation of the extensor tendon in only one out of seven hands.

Bio 3D Conduits Derived from Bone Marrow Stromal Cells Promote Peripheral Nerve Regeneration.

We previously reported that a nerve conduit created from fibroblasts promotes nerve regeneration in a rat sciatic nerve model. This study aims to determine whether a nerve conduit created from bone marrow stromal cells (BMSCs) can promote nerve regeneration. Primary BMSCs were isolated from femur bone marrow of two Lewis rats, and cells at passages 4-7 were used. We created seven Bio 3D nerve conduits from BMSCs using a Bio-3D Printer. The conduits were transplanted to other Lewis rats to bridge 5-mm right sciatic nerve gaps (Bio 3D group, n = 7). We created two control groups: a silicone group (S group, n = 5) in which the same nerve gap was bridged with a silicone tube, and a silicone cell group (SC group, n = 5) in which the gap was bridged with a BMSC injection. Twelve weeks after transplantation, nerve regeneration was evaluated functionally and morphologically. In addition, PKH26-labeled BMSCs were used to fabricate a Bio 3D conduit that was transplanted for cell trafficking analysis. Electrophysiological study, kinematic analysis, wet muscle weight, and morphological parameters showed significantly better nerve regeneration in the Bio 3D group than in the S group or SC group. In immunohistochemical studies, sections from the Bio 3D group contained abundant S-100-positive cells. In cell trafficking analysis, PKH26-positive cells stained positive for the Schwann cell markers S-100, p75NTR, and GFAP. Bio 3D nerve conduits created from BMSCs can promote peripheral nerve regeneration in a rat sciatic nerve model through BMSC differentiation into Schwann-like cells.

Pro-angiogenic scaffold-free Bio three-dimensional conduit developed from human induced pluripotent stem cell-derived mesenchymal stem cells promotes peripheral nerve regeneration.

Although autologous nerve grafting is widely accepted as the gold standard treatment for segmental nerve defects, harvesting autologous nerves is highly invasive and leads to functional loss of the ablated part. In response, artificial nerve conduits made of artificial materials have been reported, but the efficacy of the nerve regeneration still needs improvement. The purpose of this study is to investigate the efficacy and mechanism of the Bio three-dimensional (3D) conduit composed of xeno-free human induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs). The 5-mm nerve gap of the sciatic nerve in immunodeficient rats was bridged with the Bio 3D conduit or silicone tube. Functional and histological recovery were assessed at 8 weeks after surgery. The regenerated nerve in the Bio 3D group was significantly superior to that in the silicone group based on morphology, kinematics, electrophysiology, and wet muscle weight. Gene expression analyses demonstrated neurotrophic and angiogenic factors. Macroscopic observation revealed neovascularization both inside and on the surface of the Bio 3D conduit. Upon their subcutaneous implantation, iMSCs could induce angiogenesis. The Bio 3D conduit fabricated from iMSCs are an effective strategy for nerve regeneration in animal model. This technology will be useful in future clinical situations.

A scaffold-free Bio 3D nerve conduit for repair of a 10-mm peripheral nerve defect in the rats.

INTRODUCTION: A Bio 3D printed nerve conduit was reported to promote nerve regeneration in a 5 mm nerve gap model. The purpose of this study was to fabricate Bio 3D nerve conduits suitable for a 10 mm nerve gap and to evaluate their capacity for nerve regeneration in a rat sciatic nerve defect model. MATERIALS AND METHODS: Eighteen F344 rats with immune deficiency (9-10 weeks old; weight, 200-250 g) were divided into three groups: a Bio 3D nerve conduit group (Bio 3D, n = 6), a nerve graft group (NG, n = 6), and a silicon tube group (ST, n = 6). A 12-mm Bio 3D nerve conduit or silicon tube was transplanted into the 10-mm defect of the right sciatic nerve. In the nerve graft group, reverse autografting was performed with an excised 10-mm nerve segment. Assessments were performed at 8 weeks after the surgery. RESULTS: In the region distal to the suture site, the number of myelinated axons in the Bio 3D group were significantly larger compared with the silicon group (2,548 vs. 950, p < .05). The myelinated axon diameter (MAD) and the myelin thickness (MT) of the regenerated axons in the Bio 3D group were significantly larger compared with those of the ST group (MAD: 3.09 vs. 2.36 µm; p < .01; MT: 0.59 vs. 0.40 µm, p < .01). CONCLUSIONS: This study indicates that a Bio 3D nerve conduit can enhance peripheral nerve regeneration even in a 10 mm nerve defect model.

Doxorubicin-Immersed Skeletal Muscle Grafts Promote Peripheral Nerve Regeneration Across a 10-mm Defect in the Rat Sciatic Nerve.

BACKGROUND: The treatment of peripheral nerve defects requires bridging materials. Skeletal muscle grafts have been studied as an alternative to nerve autografts because they contain longitudinally aligned basal laminar tubes that are similar to axons. Several pretreatment methods for muscle grafts have promoted axonal regeneration. Here, a new method of doxorubicin pretreatment was used, and the efficacy of the pretreated muscle graft was evaluated in a rat model of a sciatic nerve defect. METHODS: A rat model of a 10-mm sciatic nerve defect was analyzed in three settings: muscle grafts with and without doxorubicin pretreatment (M-graft-w-Dox and M-graft-w/o-Dox groups, respectively) and a nerve autograft group (N-graft) (n = 6/group). The M-graft-w-Dox group was immersed in a doxorubicin solution for 10 minutes and rinsed with saline. Analyses of target muscle atrophy, electrophysiology, and histology were performed 8 weeks after grafting. RESULTS: Electrophysiological parameters and target muscle atrophy were significantly superior in the M-graft-w-Dox group compared with the M-graft-w/o-Dox group. Histological assessment revealed the presence of a significantly greater number of regenerated axons in the M-graft-w-Dox group versus the M-graft-w/o-Dox group, while there were no significant differences between the M-graft-w-Dox and N-graft groups. The diameter of myelinated axons of the regenerated nerve in the M-graft-w-Dox group was significantly larger than that in the M-graft-w/o-Dox group, while it was not significantly different compared with the N-graft group. CONCLUSION: Pretreatment of muscle grafts with doxorubicin promoted significant peripheral nerve regeneration. This method may represent a new option for the treatment of peripheral nerve defects.

Comparison of four posterior approaches of the ankle: A cadaveric study.

OBJECTIVES: The purpose of this study is to provide a detailed comparison of 4 posterior approaches of the ankle: the posteromedial, modified posteromedial (mPM), Achilles tendon-splitting (TS), and posterolateral approaches. METHODS: Cadaveric dissections were performed to assess the influence of the medial and lateral retraction forces on the neuro-vascular bundle with suspension scales and to measure the medial and lateral exposed areas of the posterior tibia and talus. Data was acquired with the ankle in neutral position and in plantar flexion. RESULTS: Both the mPM and TS approaches provided excellent visualization of the posterior tibia with the ankle in plantar flexion (16.6 cm2 and 16.2 cm2, respectively). The medial aspect of the posterior tibia, however, was significantly better exposed in the mPM approach than in the TS approach with the ankle in neutral position (8.9 cm2 vs 6.5 cm2). The lower value for medial retraction force in the mPM approach (1.9 N in neutral position and 0.9 N in plantar flexion) indicated a lower risk of injury to the neuro-vascular bundle (the tibial nerve and the posterior tibial artery). The posterior talus, however, is best visualized through the TS approach with the ankle in neutral position (4.5 cm2). CONCLUSIONS: The current study demonstrated the usefulness of the mPM approach. When internal fixation of the fibula is unnecessary, the mPM approach is preferable, considering the potential damage to the Achilles tendon associated with the TS approach.

Induced pluripotent stem cell-derived mesenchymal stem cells prolong hind limb survival in a rat vascularized composite allotransplantation model.

BACKGROUND: The reduction of systemic immunosuppressive agents is essential for the expansion of vascularized composite allotransplantation (VCA) in a clinical setting. The purpose of this study is to compare human-induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) with four other types of mesenchymal stem cells (human bone marrow-derived MSCs [BMMSCs], human adipose-derived MSCs [ADMSCs], rat BMMSCs, and rat ADMSCs) in vitro, and to investigate the in vivo immunomodulatory effect of iMSCs in a rat VCA model. MATERIALS AND METHODS: One Brown Norway (BN) rat, 2 Lewis (LEW) rats, and 1 Wistar rat were used in the mixed lymphocyte reaction (MLR), and 9 BN rats and 3 LEW rats (for donors), and 24 LEW rats (for recipients) were used in the VCA model. The abovementioned five types of MSCs were imaged to examine their morphology and were also tested for suppressor function using a MLR. The 24 recipient LEW rats were divided randomly into four groups, and subjected to orthotopic hind limb transplantation. The three control groups were the Iso group, in which transplantation was performed on from three to six LEW rats without immunosuppressive treatment (n = 6); the FK group, in which transplantation was performed from BN rats to LEW rats and recipient rats were treated with tacrolimus alone (FK 506, 0.2 mg/kg, days 0-6 postoperatively, intraperitoneally) (n = 6); and the UT group, in which transplantation was performed from BN rats to LEW rats without any immunosuppressive treatment (n = 6). The experimental group was the iMSC group, in which transplantation was performed from BN rats to LEW rats and recipient rats were treated with tacrolimus (FK 506, 0.2 mg/kg, days 0-6 postoperatively, intraperitoneally) and injected with iMSCs (2 × 106 cells, day 7, intravenously) (n = 6). Hind limb survival was assessed by daily inspection of gross appearance until 50 days postoperatively. Histology of the skin and muscle biopsy were investigated on day 14 postoperatively. A time series of the plasma cytokine level (before transplantation, and at 10, 14, and 17 days after transplantation) was also analyzed. RESULTS: The size of adherent and trypsinized iMSCs was 67.5 ± 8.7 and 9.5 ± 1.1 µm, respectively, which was the smallest among the five types of MSCs (p < .01). The absorbance in MLR was significantly smaller with rat ADMSCs (p = .0001), human iMSCs (p = .0006), rat BMMSCs (p = .0014), human ADMSCs (p = .0039), and human BMMSCs (p = .1191) compared to without MSCs. In vivo, iMSC treatment prolonged hind limb survival up to 12.7 days in macroscopic appearance, which is significantly longer than that of the FK group (p < .01). Histology of the skin and muscle biopsy revealed that mononuclear cell infiltration was significantly reduced by iMSC injection (p < .01). iMSC treatment also affected proinflammatory cytokines (interferon-gamma (IFNγ) and tumor necrosis factor α (TNFα)) and the anti-inflammatory cytokine (interleukin-10 (IL-10)) of the recipient plasma. The IFNγ levels at Δ14 and the TNFα levels at Δ14 and Δ17 of the iMSC group were significantly lower than those of the FK group (p = .0226, .0004, and .004, respectively). The IL-10 levels at Δ10 and Δ14 of the iMSC group were significantly higher than those of the FK group (p = .0013 and .0374, respectively). CONCLUSIONS: iMSCs induce T cell hyporesponsiveness to prolong hind limb survival in a rat VCA model. This immunomodulatory property against acute rejection could provide one of the promising strategies capable of enabling the toxicities of immunosuppressants to be avoided in clinical settings.

The Efficacy of a Scaffold-free Bio 3D Conduit Developed from Autologous Dermal Fibroblasts on Peripheral Nerve Regeneration in a Canine Ulnar Nerve Injury Model: A Preclinical Proof-of-Concept Study.

Autologous nerve grafting is widely accepted as the gold standard treatment for segmental nerve defects. To overcome the inevitable disadvantages of the original method, alternative methods such as the tubulization technique have been developed. Several studies have investigated the characteristics of an ideal nerve conduit in terms of supportive cells, scaffolds, growth factors, and vascularity. Previously, we confirmed that biological scaffold-free conduits fabricated from human dermal fibroblasts promote nerve regeneration in a rat sciatic nerve injury model. The purpose of this study is to evaluate the feasibility of biological scaffold-free conduits composed of autologous dermal fibroblasts using a large-animal model. Six male beagle dogs were used in this study. Eight weeks before surgery, dermal fibroblasts were harvested from their groin skin and grown in culture. Bio 3D conduits were assembled from proliferating dermal fibroblasts using a Bio 3D printer. The ulnar nerve in each dog's forelimb was exposed under general anesthesia and sharply cut to create a 5 mm interstump gap, which was bridged by the prepared 8 mm Bio 3D conduit. Ten weeks after surgery, nerve regeneration was investigated. Electrophysiological studies detected compound muscle action potentials (CMAPs) of the hypothenar muscles and motor nerve conduction velocity (MNCV) in all animals. Macroscopic observation showed regenerated ulnar nerves. Low-level hypothenar muscle atrophy was confirmed. Immunohistochemical, histological, and morphometric studies confirmed the existence of many myelinated axons through the Bio 3D conduit. No severe adverse event was reported. Hypothenar muscles were re-innervated by regenerated nerve fibers through the Bio 3D conduit. The scaffold-free Bio 3D conduit fabricated from autologous dermal fibroblasts is effective for nerve regeneration in a canine ulnar nerve injury model. This technology was feasible as a treatment for peripheral nerve injury and segmental nerve defects in a preclinical setting.