論文

• The effect of KUS121, a novel VCP modulator, against ischemic injury in random pattern flaps

  Koichi Yoshimoto; Ryosuke Ikeguchi; Takashi Noguchi; Maki Ando; Daichi Sakamoto; Terunobu Iwai; Kohei Nishitani; Hanako Ohashi Ikeda; Akira Kakizuka; Shuichi Matsuda

  PLOS ONE 2024年12月
• Nerve regeneration using a Bio 3D conduit derived from umbilical cord–Derived mesenchymal stem cells in a rat sciatic nerve defect model

  Terunobu Iwai; Ryosuke Ikeguchi; Tomoki Aoyama; Takashi Noguchi; Koichi Yoshimoto; Daichi Sakamoto; Kazuaki Fujita; Yudai Miyazaki; Shizuka Akieda; Tokiko Nagamura-Inoue; Fumitaka Nagamura; Koichi Nakayama; Shuichi Matsuda

  PLOS ONE 2024年12月
• Fabrication of Artificial Nerve Conduits Used in a Long Nerve Gap: Current Reviews and Future Studies.

  Ryosuke Kakinoki; Yukiko Hara; Koichi Yoshimoto; Yukitoshi Kaizawa; Kazuhiko Hashimoto; Hiroki Tanaka; Takaya Kobayashi; Kazuhiro Ohtani; Takashi Noguchi; Ryosuke Ikeguchi; Masao Akagi; Koji Goto

  Bioengineering (Basel, Switzerland) 11 4 2024年04月 

  There are many commercially available artificial nerve conduits, used mostly to repair short gaps in sensory nerves. The stages of nerve regeneration in a nerve conduit are fibrin matrix formation between the nerve stumps joined to the conduit, capillary extension and Schwann cell migration from both nerve stumps, and, finally, axon extension from the proximal nerve stump. Artificial nerves connecting transected nerve stumps with a long interstump gap should be biodegradable, soft and pliable; have the ability to maintain an intrachamber fibrin matrix structure that allows capillary invasion of the tubular lumen, inhibition of scar tissue invasion and leakage of intratubular neurochemical factors from the chamber; and be able to accommodate cells that produce neurochemical factors that promote nerve regeneration. Here, we describe current progress in the development of artificial nerve conduits and the future studies needed to create nerve conduits, the nerve regeneration of which is compatible with that of an autologous nerve graft transplanted over a long nerve gap.
• Clinical Results of Arthroscopic Partial Trapeziectomy With Suture-Button Suspensionplasty for Thumb Carpometacarpal Arthritis.

  Akemi Maeda; Ryosuke Ikeguchi; Takashi Noguchi; Rie Yamawaki; Manabu Nankaku; Maki Ando; Koichi Yoshimoto; Daichi Sakamoto; Shuichi Matsuda

  Hand (New York, N.Y.) 18 5 740 - 745 2023年07月 

  BACKGROUND: This study represents the clinical results, especially range of motion (ROM) improvement, of arthroscopic partial trapeziectomy with suture-button suspensionplasty for symptomatic grade II and III thumb carpometacarpal arthritis with a minimum 1-year follow-up. METHODS: Thirty-two patients (mean: 67.5 years) with grade II and III thumb carpometacarpal arthritis treated with arthroscopic partial trapeziectomy with suture-button suspensionplasty were retrospectively followed up for at least 1 year. The physical assessments included ROM, pain visual analogue scale (VAS), strength, and the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire. The physical variables were retrospectively compared before surgery and at the final follow-up. RESULTS: Preoperative radial abduction and palmar abduction (45.4 ± 16.4° and 54.3 ± 13.9°, respectively) were significantly increased at the final follow-up (59.7 ± 16.9° and 65.5 ± 14.2°, respectively). Preoperative VAS score, pinch strength, and DASH score (70.5 ± 14.0, 57.2 ± 24.8% and 36.8 ± 14.8, respectively) were also significantly improved at the final follow-up (7.9 ± 9.1, 91.0 ± 39.6%, and 11.7 ± 10.5, respectively). Complications involved 1 case of irritation of the superficial branch of the radial nerve and 1 case of dystonia. Two suture-buttons were removed due to patient discomfort. CONCLUSIONS: A significant increase in ROM and pain relief was obtained after suture-button suspensionplasty with arthroscopic partial trapeziectomy.
• Radiographic Evaluation after Arthroscopic Partial Trapeziectomy with Suture-button Suspensionplasty for Thumb Carpometacarpal Arthritis.

  Yuki Shinya; Ryosuke Ikeguchi; Takashi Noguchi; Maki Ando; Koichi Yoshimoto; Daichi Sakamoto; Terunobu Iwai; Shuichi Matsuda

  Plastic and reconstructive surgery. Global open 11 5 e4983  2023年05月 

  UNLABELLED: Arthroscopic partial trapeziectomy with suture-button suspensionplasty was developed for the surgical treatment of thumb carpometacarpal arthritis. However, the relationship between clinical results and radiographic evidence is unclear. METHODS: The authors retrospectively reviewed 33 consecutive patients who underwent arthroscopic partial trapeziectomy with suture-button suspensionplasty for thumb carpometacarpal arthritis between 2016 and 2021. Clinical and radiographic outcomes were recorded, and the correlations between them were evaluated. RESULTS: The average patient age at surgery was 69 years. Patient radiologic evidence was Eaton stage Ⅱ in three thumbs, Ⅲ in 25 thumbs, and Ⅳ in five thumbs. The average trapezial space ratio (TSR) was 0.36 immediately after the operation but declined to 0.32 after 6 months. In contrast, the average joint subluxation was reduced to 0.005 immediately after the operation compared with 0.28 before, and was maintained at 0.04 at final follow-up. A statically significant correlation was detected between grip strength and TSR (P = 0.03), and between pinch strength and TSR (P = 0.02). A significant correlation was detected between TSR and trapezium height (P = 0.0215), which remained after partial trapeziectomy. No correlation was detected between rope position and other clinical or radiographic scores. CONCLUSIONS: Suture-button can have an effect on the medialization of the first metacarpal base. Excessive trapeziectomy can result in functional deficiency of the thumb through metacarpal subsidence, which potentially causes loss of grip and pinch strength.
• Muscle Grafts with Doxorubicin Pretreatment Produce "Empty Tubes" in the Basal Laminae, Promote Contentious Maturation of the Regenerated Axons, and Bridge 20-mm Sciatic Nerve Defects in Rats.

  Hisataka Takeuchi; Akio Sakamoto; Ryosuke Ikeguchi; Souichi Ohta; Takashi Noguchi; Maki Ando; Koichi Yoshimoto; Daichi Sakamoto; Shuichi Matsuda

  Journal of reconstructive microsurgery 39 2 120 - 130 2023年02月 

  BACKGROUND:  We newly developed a muscle graft that employs a doxorubicin pretreatment technique. The aims of this study were to reveal the biological and morphological features of the muscle tissue in the second week (Study I), to reveal the regeneration outcomes of functional and kinematic assessments of longer-term follow-up (16 weeks, Study II), and to make assessments of the muscle graft with doxorubicin pretreatment in the critical-sized nerve defect model (20 mm, Study III). METHODS:  A total of 26 adult rats were used in this study. Doxorubicin treatment was accomplished by immersion in a doxorubicin solution for 10 minutes followed by a rinsing procedure. The rats were divided into three groups: the muscle graft with and without doxorubicin pretreatment (M-graft-w-Dox and M-graft-w/o-Dox) groups and the autologous nerve graft (N-graft) group. Assays of apoptosis, immunofluorescent histochemistry including CD68 (macrophage marker), scanning electron microscopy (SEM), morphometrical studies of the regenerated axons, nerve conduction studies, and kinematic studies were performed. RESULTS:  The M-graft-w-Dox group contained significantly larger numbers of apoptotic cells and CD68-positive cells. SEM revealed the existence of the basal lamina, so called "empty tubes," in the M-graft-w-Dox group. Study II showed contentious maturation of the regenerated axons, especially in the compound muscle action potentials. Study III showed that even at 20 mm, the M-graft-w-Dox group promoted axonal regeneration and functional regeneration. CONCLUSION:  The M-graft-w-Dox group showed superior regeneration results, and this easy and short-term procedure can expand the muscle graft clinical indication for the treatment of peripheral nerve defects.
• Nerve regeneration using the Bio 3D nerve conduit fabricated with spheroids.

  Ryosuke Ikeguchi; Tomoki Aoyama; Mai Tanaka; Takashi Noguchi; Maki Ando; Koichi Yoshimoto; Daichi Sakamoto; Terunobu Iwai; Yudai Miyazaki; Shizuka Akieda; Makoto Ikeya; Koichi Nakayama; Shuichi Matsuda

  Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs 25 4 289 - 297 2022年12月 

  Autologous nerve grafting is the gold standard method for peripheral nerve injury with defects. Artificial nerve conduits have been developed to prevent morbidity at the harvest site. However, the artificial conduit regeneration capacity is not sufficient. A Bio 3D printer is technology that creates three-dimensional tissue using only cells. Using this technology, a three-dimensional nerve conduit (Bio 3D nerve conduit) was created from several cell spheroids. We reported the first application of the Bio 3D nerve conduit for peripheral nerve injury. A Bio 3D nerve conduit that was created from several cells promotes peripheral nerve regeneration. The Bio 3D nerve conduit may be useful clinically to treat peripheral nerve defects.
• Anterolateral thigh flap for upper extremity reconstruction in older patients.

  Ryosuke Ikeguchi; Takashi Noguchi; Maki Ando; Koichi Yoshimoto; Daichi Sakamoto; Shuichi Matsuda

  Microsurgery 42 8 793 - 799 2022年11月 

  BACKGROUND: The anterolateral thigh (ALT) flap has been used in upper extremity reconstruction. However, there is no consensus about the age at which the flap can be used safely, which is a concern when applying ALT flaps for upper extremity reconstruction in older patients. We present the results of the use of ALT flap for upper extremity reconstruction in a series of older patients. PATIENTS AND METHODS: Seventeen patients who underwent ALT flaps for soft tissue defects in the upper extremities from 2010 to 2020 were included. The patients' mean age was 63.5 (range, 26-83) years. Ten of seventeen patients were smokers. Defect locations were the dorsum of the hand in seven patients, palm in two patients, dorsum and palm in two patients, and forearm in six patients. Etiologies of the defect were traumatic in 14 patients and malignant tumor in three patients. The defect size was 8 to 25 × 5 to 11 cm. When dissecting the perforators, we preserved the surrounding small muscular and fatty tissue with the perforators and to harvest them together to prevent intima damage. Flap thinning was performed for 16 flaps to adjust the flap thickness to match defect site requirements. We used an end-to-side or interposition arterial anastomosis to regulate the blood flow. RESULTS: The flap size was 9 to 28 × 5 to 13 cm. One patient had venous congestion and vein re-anastomosis was needed. All flaps survived. One patient had a methicillin-resistant Staphylococcus aureus infection and debridement and irrigation was needed. The mean follow-up period was 20 (range, 13-37) months. Fifteen patients returned their previous activities. The mean DASH score was 30.6 (range, 3-70). CONCLUSIONS: Regardless of patient age or smoking status, the ALT flap was a safe and reliable surgical option for soft tissue defect reconstruction of the upper extremity.
• Enthesopathy of the bicipital tuberosity of the radius treated under intraoperative computed tomography.

  Ryosuke Ikeguchi; Takashi Noguchi; Maki Ando; Koichi Yoshimoto; Daichi Sakamoto; Shuichi Matsuda

  European journal of medical research 27 1 34 - 34 2022年03月 

  BACKGROUND: There is no report of the application of intraoperative computed tomography to the extremities, and its usefulness is not mentioned. CASE PRESENTATION: We present a case of a patient with the elbow pain and loss of the forearm rotation due to the prominent bicipital tuberosity of the radius, which was diagnosed as enthesopathy. Surgical treatment to excise the prominent part of the bicipital tuberosity of the radius was recommended. However, it is difficult to perform the appropriate excision of the abnormal prominent part because of complications such as bicipital tendon rupture. The patient was successfully treated by surgical resection under the control of intraoperative computed tomography. CONCLUSIONS: Intraoperative computed tomography scan is a useful tool to assess the remaining volume of the abnormal bones.
• The efficacy of combining a vascularized biogenic conduit and a decellularized nerve graft in the treatment of peripheral nerve defects: An experimental study using the rat sciatic nerve defect model.

  Hisataka Takeuchi; Ryosuke Ikeguchi; Takashi Noguchi; Maki Ando; Koichi Yoshimoto; Daichi Sakamoto; Shuichi Matsuda

  Microsurgery 42 3 254 - 264 2022年03月 

  BACKGROUND: Although decellularized nerve grafts are often used as a bridging material in nerve defect repair, the lack of perfusion support in this procedure limits the regeneration capacity. To address this, we applied vascularized biogenic conduits, which are fibrous membranes prefabricated around the silicone rod that contain rich vascularity and macrophages, to nerve defect repair procedures using decellularized nerve grafts. The purpose of this study is to investigate the capacity of combining a vascularized biogenic conduit and a decellularized nerve graft for peripheral nerve regeneration using a 10-mm nerve defect model in rats. MATERIALS AND METHODS: Sixteen adult male rats (F344 rats, 10-12 weeks, 200-250 g) were used in this study. For the prefabrication of vascularized biogenic conduits, a silicone rod was transplanted next to the sciatic nerve. After 8 weeks, this silicone rod was enveloped in connective tissue, called a vascularized biogenic conduit. The first rat was used to investigate the histological characteristics of vascularized biogenic conduits through immunofluorescence studies. The remaining 15 rats were divided into three groups to evaluate the efficacy of the combination of a decellularized nerve graft and a vascularized biogenic conduit: a decellularized nerve graft (DNG) group, a decellularized nerve graft with a vascularized biogenic conduit (DNG-w-VBC) group, and an autologous nerve graft (ANG) group. Eight weeks after nerve graft surgery, the assessment results of both functional recovery (electrophysical studies and target muscle atrophy) and morphological recovery (total number, diameter, and myelin thickness of the regenerated axons) of the regenerated nerves were examined. RESULTS: Immunofluorescence studies revealed that the VBC contains extracellular matrix, vascular tissue, and macrophages. The results of the DNG-w-VBC group were superior to the DNG group in electrophysiological studies (CMAP; 6.29 ± 0.80% vs. 4.02 ± 3.35%, MNCV; 50.6 ± 8.4% vs. 25.7 ± 15.6%, p < .05, respectively), regenerated axon number (11,348 ± 812 vs. 7697 ± 2197, p < .05), and mean axon diameter (2.72 ± 0.33 μm vs. 1.64 ± 0.12 μm, p < .05). CONCLUSIONS: Our study confirms that vascularized biogenic conduits supply vascularity and macrophages to nerve defect sites. Combining vascularized biogenic conduits with decellularized nerve grafts to treat nerve defects offers superior functional and morphological recovery of regenerated axons.
• Mechanism of Peripheral Nerve Regeneration Using a Bio 3D Conduit Derived from Normal Human Dermal Fibroblasts.

  Hirofumi Yurie; Ryosuke Ikeguchi; Tomoki Aoyama; Akira Ito; Mai Tanaka; Takashi Noguchi; Hiroki Oda; Hisataka Takeuchi; Sadaki Mitsuzawa; Maki Ando; Koichi Yoshimoto; Shizuka Akieda; Koichi Nakayama; Shuichi Matsuda

  Journal of reconstructive microsurgery 37 4 357 - 364 2021年05月 

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

  Hirofumi Yurie; Ryosuke Ikeguchi; Tomoki Aoyama; Mai Tanaka; Hiroki Oda; Hisataka Takeuchi; Sadaki Mitsuzawa; Maki Ando; Koichi Yoshimoto; Takashi Noguchi; Shizuka Akieda; Koichi Nakayama; Shuichi Matsuda

  Cell transplantation 29 963689720951551 - 963689720951551 2020年 

  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.