Honors & Awards
Travel Award in Orthopaedic Research Translation, ORS (2018)
JOSSM USA-Travelling fellowship award, The Japanese Orthopaedic Society for Sports Medicine (2017)
Doctor of Philosophy, Yamagata University Faculty of Medicine, Japan (2018)
Doctor of Medicine, Yamagata University Faculty of Medicine, Japan (2004)
- Modulation of the Inflammatory Response and Bone Healing FRONTIERS IN ENDOCRINOLOGY 2020; 11
Macrophage Effects on Mesenchymal Stem Cell Osteogenesis in a Three-Dimensional in vitro Bone Model.
Tissue engineering. Part A
As musculoskeletal disorders continue to increase globally, there is an increased need for novel, in vitro models to efficiently study human bone physiology in the context of both healthy and diseased conditions. For these models, the inclusion of innate immune cells is critical. Specifically, signaling factors generated from macrophages play key roles in the pathogenesis of many musculoskeletal processes and diseases, including fracture, osteoarthritis, infection, etc. In this study, we aim to engineer three-dimensional (3D) and macrophage-encapsulated bone tissues in vitro, to model cell behavior, signaling, and other biological activities in vivo, in comparison to current two-dimensional (2D) models. We first investigated and optimized 3D culture conditions for macrophages, and then co-cultured macrophages with mesenchymal stem cells (MSCs) which were induced to undergo osteogenic differentiation to examine the effect of macrophage on new bone formation. Seeded within a 3D hydrogel scaffold fabricated from photocrosslinked methacrylated gelatin, macrophages maintained high viability and were polarized toward an M1 or M2 phenotype. In co-cultures of macrophages and human MSCs, MSCs displayed immunomodulatory activities by suppressing M1 and enhancing M2 macrophage phenotypes. Lastly, addition of macrophages, regardless of polarization state, increased MSC osteogenic differentiation, compared to MSCs alone, with pro-inflammatory M1 macrophages enhancing new bone formation most effectively. In summary, this study illustrates the important roles that macrophage signaling and inflammation play in bone tissue formation.
View details for DOI 10.1089/ten.TEA.2020.0041
View details for PubMedID 32312178
The efficacy of core decompression for steroidassociated osteonecrosisof the femoral head in rabbits.
Journal of orthopaedic research : official publication of the Orthopaedic Research Society
Although core decompression (CD) is often performed in the early stages of osteonecrosis of the femoral head (ONFH), the procedure does not always prevent subsequent deterioration and the effects of CD are not fully clarified.The aim of this study was to evaluate the efficacy of CD for steroid associated ONFH in rabbits.Twelve male and twelve female New Zealand rabbits were injected intramuscularly 20 mg/kg of methylprednisolone once and were divided into the disease control and CD groups. In the disease control group, rabbits had no treatment and were euthanized at 12 weeks post-injection. In the CD group, rabbits underwent left femoral CD at 4 weeks post-injection and were euthanized 8 weeks postoperatively. The left femurs were collected to perform morphological, biomechanical and histological analysis.Bone mineral density and bone volume fraction in the femoral head in the CD group were significantly higher than in the disease control group. However, no difference in the mechanical strength was observed between the two groups. Histological analysis showed thatalkaline phosphatase and CD31 positive cells significantly increased in the males after CD treatment. The number of empty lacunae in the surrounding trabecular bone was significantly higher in the CD group.The current study indicated that CD improved the morphological properties, but did not improve the mechanical strength in the femoral headat early stage ONFH.These data suggest the need for additional biological, mechanical strategies,and therapeutic windows to improve the outcome of early stage steroid associated ONFH. This article is protected by copyright. All rights reserved.
View details for DOI 10.1002/jor.24888
View details for PubMedID 33095462
IL-4 Overexpressing Mesenchymal Stem Cells within Gelatin-Based Microribbon Hydrogels Enhance Bone Healing in a Murine Long Bone Critical-size Defect Model.
Journal of biomedical materials research. Part A
Mesenchymal stem cell (MSC)-based therapy is a promising strategy for bone repair. Furthermore, the innate immune system, and specifically macrophages, play a crucial role in the differentiation and activation of MSCs. The anti-inflammatory cytokine IL-4 converts pro-inflammatory M1 macrophages into a tissue regenerative M2 phenotype, which enhances MSC differentiation and function. We developed lentivirus-transduced IL-4 over-expressing MSCs (IL-4 MSCs) that continuously produce IL-4 and polarize macrophages toward an M2 phenotype. In the current study, we investigated the potential of IL-4 MSCs delivered using a macroporous gelatin-based microribbon (μRB) scaffold for healing of critical size long bone defects in Mice. IL-4 MSCs within μRBs enhanced M2 marker expression without inhibiting M1 marker expression in the early phase, and increased macrophage migration into the scaffold. Six weeks after establishing the bone defect, IL-4 MSCs within μRBs enhanced bone formation and helped bridge the long bone defect. IL-4 MSCs delivered using macroporous μRB scaffold is potentially a valuable strategy for the treatment of critical size long bone defects. This article is protected by copyright. All rights reserved.
View details for DOI 10.1002/jbm.a.36982
View details for PubMedID 32363683
Modulation of the Inflammatory Response and Bone Healing.
Frontiers in endocrinology
2020; 11: 386
The optimal treatment for complex fractures and large bone defects is an important unsolved issue in orthopedics and related specialties. Approximately 5-10% of fractures fail to heal and develop non-unions. Bone healing can be characterized by three partially overlapping phases: the inflammatory phase, the repair phase, and the remodeling phase. Eventual healing is highly dependent on the initial inflammatory phase, which is affected by both the local and systemic responses to the injurious stimulus. Furthermore, immune cells and mesenchymal stromal cells (MSCs) participate in critical inter-cellular communication or crosstalk to modulate bone healing. Deficiencies in this inter-cellular exchange, inhibition of the natural processes of acute inflammation, and its resolution, or chronic inflammation due to a persistent adverse stimulus can lead to impaired fracture healing. Thus, an initial and optimal transient stage of acute inflammation is one of the key factors for successful, robust bone healing. Recent studies demonstrated the therapeutic potential of immunomodulation for bone healing by the preconditioning of MSCs to empower their immunosuppressive properties. Preconditioned MSCs (also known as "primed/ licensed/ activated" MSCs) are cultured first with pro-inflammatory cytokines (e.g., TNFα and IL17A) or exposed to hypoxic conditions to mimic the inflammatory environment prior to their intended application. Another approach of immunomodulation for bone healing is the resolution of inflammation with anti-inflammatory cytokines such as IL4, IL10, and IL13. In this review, we summarize the principles of inflammation and bone healing and provide an update on cellular interactions and immunomodulation for optimal bone healing.
View details for DOI 10.3389/fendo.2020.00386
View details for PubMedID 32655495
View details for PubMedCentralID PMC7325942
- Osteogenic ability of rat bone marrow concentrate is at least as efficacious as mesenchymal stem cells in vitro JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS 2019; 107 (8): 2500–2506
The Effect of Mesenchymal Stem Cell Sheets on Early Healing of the Achilles Tendon in Rats.
Tissue engineering. Part A
Bone marrow-derived mesenchymal stem cells (BMSCs) have potential to accelerate flexor tendon healing and allow for earlier rehabilitation. The ideal BMSC construct and delivery method to the repair site remains unknown. We investigated the efficacy of interposed scaffold-free BMSC sheets on early Achilles tendon healing in rats. BMSCs were isolated from the femora and tibias of male Sprague-Dawley rats aged 8 to 12 weeks and BMSC sheets were produced on temperature-responsive culture dishes. Ninety-five male Sprague-Dawley rats aged 8 to 12 weeks were utilized. A bilateral Achilles tendon repair model was created. One side was randomly selected, and the tendon was repaired with the interposed BMSC sheet (BMSC group). The other side was repaired without BMSCs (control group). The bilateral tendons were harvested at 5, 6, 7, 10 and 14 days postoperatively for biomechanical analysis, measurement of the gene expression level of tendon markers scleraxis and/or tenomodulin by real-time polymerase chain reaction, and histological evaluation. The BMSC group had significantly higher maximum load to failure and stiffness at 5 and 6 days compared to the control group. Moreover, the BMSC group showed significantly increased gene expression of scleraxis and/or tenomodulin at all timepoints. The cross sectional areas in the BMSC group were significantly larger at 5, 6 and 14 days. However, Hematoxylin and Eosin staining of the central part of the repair site revealed no significant differences at all timepoints These results suggest that the increased biomechanical strength afforded by BMSC sheet implantation into tendon repair sites may allow for the earlier onset of rehabilitation and improved clinical outcomes in flexor tendon surgery.
View details for DOI 10.1089/ten.TEA.2019.0163
View details for PubMedID 31608794
- Cell-Based and Scaffold-Based Therapies for Joint Preservation in Early-Stage Osteonecrosis of the Femoral Head: A Review of Basic Research. JBJS reviews 2019
- Treating Titanium Particle-Induced Inflammation with Genetically Modified NF-kappa B Sensing IL-4 Secreting or Preconditioned Mesenchymal Stem Cells in Vitro ACS BIOMATERIALS SCIENCE & ENGINEERING 2019; 5 (6): 3032–38
- Preconditioned or IL4-Secreting Mesenchymal Stem Cells Enhanced Osteogenesis at Different Stages TISSUE ENGINEERING PART A 2019
- Mesenchymal stem cell-macrophage crosstalk and bone healing BIOMATERIALS 2019; 196: 80–89
Treating Titanium Particle-Induced Inflammation with Genetically Modified NF-κB Sensing IL-4 Secreting or Preconditioned Mesenchymal Stem Cells in Vitro.
ACS biomaterials science & engineering
2019; 5 (6): 3032–38
Titanium and titanium-based alloys are widely used in orthopaedic implants. Total joint replacement is very successful; however, the foreign body response and chronic inflammation caused by implant-derived biomaterial debris still remain as unsolved issues. Aseptic loosening accompanied by wear debris-induced osteolysis (bone loss) is one of the most frequent causes for late failure and revision surgery. Mesenchymal stem cells (MSCs) and IL-4 may be possible treatment strategies because of their immunomodulatory properties. We investigated the efficacy of novel MSC-based treatments on immunomodulation and osteogenic differentiation in an innovative cell coculture model of titanium particle-induced inflammation in the periprosthetic tissues. MSCs and macrophages were collected from the bone marrow of Balb/c mice. Both MSCs and macrophages (representing endogenous cells at the periprosthetic tissue) were seeded on the bottom wells of the 24-well transwell plates. We generated genetically modified NF-κB sensing IL-4 secreting MSCs (inflammatory responsive MSCs) and MSCs preconditioned by lipopolysaccharide and TNF-α to further enhance their immunomodulatory function. These modified MSCs (representing exogenous therapeutic cells implanted to the periprosthetic tissue) were seeded on the upper chambers of the transwell plates. These cocultures were then exposed to titanium particles for 7 days. NF-κB sensing IL-4 secreting MSCs showed strong immunomodulation (significantly reduced TNF-α and induced Arg1 expression) and promoted early osteogenesis (significantly induced Runx2, ALP, and β-catenin as well as reduced Smurf2 expression) at day 7. IL-4 secreting MSCs also decreased TNF-α protein secretion as early as day 3 and increased IL-1ra protein secretion at day 7, suggesting efficacious immunomodulation of particle-induced inflammation. Preconditioned MSCs did not show significant immunomodulation in this short-term experiment, but ALP and β-catenin expression were significantly induced at day 7. Our results suggest that genetically modified IL-4 secreting MSCs and preconditioned MSCs have the potential to optimize bone regeneration in inflammatory conditions including periprosthetic osteolysis.
View details for DOI 10.1021/acsbiomaterials.9b00560
View details for PubMedID 32391436
View details for PubMedCentralID PMC7207059
Optimization and characterization of calcium phosphate transfection in mesenchymal stem cells.
Tissue engineering. Part C, Methods
Mesenchymal stem cells (MSCs) have been used as a therapy to modulate diverse biological processes. To fulfill the requirements for different MSC therapies, safe and effective gene transfer methods for MSCs are critical. Calcium phosphate transfection is an inexpensive and well-described method without discernible biosafety issues; however, an optimal protocol has not been developed for MSCs. In this report, we optimized the protocol of calcium phosphate transfection for murine MSCs, and compared this protocol with other gene transfer methods in different strains of mice and in human cells. We found that transfection efficiency and cell viability showed an inverse relationship depending on serum concentration during the process of calcium phosphate transfection, in which 2% serum was chosen in the optimized protocol. The optimized protocol of calcium phosphate transfection showed a fine balance between efficiency (about 70-80%) and viability (doubling original cell number) compared to other methods. Human MSCs were more resistant to this protocol (about 30% efficiency) compared with murine MSCs. Moreover, MSC potential for osteogenesis, adipogenesis, and chondrogenesis was not affected by calcium phosphate transfection. Finally, MSCs transfected with the luciferase gene were injected into the murine distal femoral bone marrow cavity to monitor gene expression overtime in vivo. MSCs in the bone marrow environment showed extended expression of the luciferase that was transfected by calcium phosphate. This report provides an optimized protocol for calcium phosphate transfection for murine MSCs and characterizes gene over-expression in MSCs in the in vitro and in vivo environments.
View details for DOI 10.1089/ten.TEC.2019.0147
View details for PubMedID 31441373
Precise immunomodulation of the M1 to M2 macrophage transition enhances mesenchymal stem cell osteogenesis and differs by sex.
Bone & joint research
2019; 8 (10): 481–88
Up to 10% of fractures result in undesirable outcomes, for which female sex is a risk factor. Cellular sex differences have been implicated in these different healing processes. Better understanding of the mechanisms underlying bone healing and sex differences in this process is key to improved clinical outcomes. This study utilized a macrophage-mesenchymal stem cell (MSC) coculture system to determine: 1) the precise timing of proinflammatory (M1) to anti-inflammatory (M2) macrophage transition for optimal bone formation; and 2) how such immunomodulation was affected by male versus female cocultures.A primary murine macrophage-MSC coculture system was used to demonstrate the optimal transition time from M1 to M2 (polarized from M1 with interleukin (IL)-4) macrophages to maximize matrix mineralization in male and female MSCs. Outcome variables included Alizarin Red staining, alkaline phosphatase (ALP) activity, and osteocalcin protein secretion.We found that 96 hours of M1 phenotype in male cocultures allowed for maximum matrix mineralization versus 72 hours in female cocultures. ALP activity and osteocalcin secretion were also enhanced with the addition of IL-4 later in male versus female groups. The sex of the cells had a statistically significant effect on the optimal IL-4 addition time to maximize osteogenesis.These results suggest that: 1) a 72- to 96-hour proinflammatory environment is critical for optimal matrix mineralization; and 2) there are immunological differences in this coculture environment due to sex. Optimizing immunomodulation during fracture healing may enhance and expedite the bone regeneration response. These findings provide insight into precise immunomodulation for enhanced bone healing that is sex-specific.Cite this article: K. Nathan, L. Y. Lu, T. Lin, J. Pajarinen, E. Jämsen, J-F. Huang, M. Romero-Lopez, M. Maruyama, Y. Kohno, Z. Yao, S. B. Goodman. Precise immunomodulation of the M1 to M2 macrophage transition enhances mesenchymal stem cell osteogenesis and differs by sex. Bone Joint Res 2019;8:481-488. DOI: 10.1302/2046-3758.810.BJR-2018-0231.R2.
View details for DOI 10.1302/2046-3758.810.BJR-2018-0231.R2
View details for PubMedID 31728188
View details for PubMedCentralID PMC6825050
Trained murine mesenchymal stem cells have anti-inflammatory effect on macrophages, but defective regulation on T-cell proliferation.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Mesenchymal stem cell (MSC)-mediated immunomodulation affects both innate and adaptive immune systems. These responses to environmental cues, such as pathogen-associated molecular patterns, damage-associated molecular patterns, or proinflammatory cytokines, are crucial for resolution of inflammation, as well as successful tissue healing and regeneration. We observed that intermittent, repeated exposure of MSCs to LPS induced stronger NF-kappaB activation than singular stimulation. A similar phenomenon, named innate immune memory or trained immunity, has been reported with macrophages. However, the potential regulation of "immune memory" in nonclassic immune cells, such as MSCs, has not been reported. In the current study, we chose IFN-gamma plus TNF-alpha restimulation-induced iNOS expression as a model of MSC activation, because IFN-gamma and TNF-alpha play crucial roles in MSC-mediated immunomodulation. The iNOS expression was enhanced in LPS-trained MSCs, 3 d after a washout period following primary stimulation. LPS-trained MSCs enhanced the anti-inflammatory (arginase 1 and CD206) marker expression, but decreased the proinflammatory marker (TNF-alpha, IL-1beta, iNOS, and IL-6) expression using an MSC-macrophage coculture model. In contrast, LPS-trained MSCs demonstrated a defective regulation on CD4 T-cell proliferation. Mechanistic studies suggested that histone methylation and the JNK pathway are involved in LPS-trained immunomodulation in MSCs. Our results demonstrate differential immunomodulatory effects of trained MSCs on macrophages and T cells. These immunomodulatory consequences are critical, because they will have a major impact on current MSC-based cell therapies.-Lin, T., Pajarinen, J., Kohno, Y., Huang, J.-F., Maruyama, M., Romero-Lopez, M., Nathan, K., Yao, Z., Goodman, S. B. Trained murine mesenchymal stem cells have anti-inflammatory effect on macrophages, but defective regulation on T-cell proliferation.
View details for PubMedID 30521384
- The effects of a functionally-graded scaffold and bone marrow-derived mononuclear cells on steroid-induced femoral head osteonecrosis BIOMATERIALS 2018; 187: 39–46
- NF kappa B sensing IL-4 secreting mesenchymal stem cells mitigate the proinflammatory response of macrophages exposed to polyethylene wear particles JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A 2018; 106 (10): 2744–52
Transplanted interleukin-4--secreting mesenchymal stromal cells show extended survival and increased bone mineral density in the murine femur.
BACKGROUND: Mesenchymal stromal cell (MSC)-based therapy has great potential to modulate chronic inflammation and enhance tissue regeneration. Crosstalk between MSC-lineage cells and polarized macrophages is critical for bone formation and remodeling in inflammatory bone diseases. However, the translational application of this interaction is limited by the short-term viability of MSCs after cell transplantation.METHODS: Three types of genetically modified (GM) MSCs were created: (1) luciferase-expressing reporter MSCs; (2) MSCs that secrete interleukin (IL)-4 either constitutively; and (3) MSCs that secrete IL-4 as a response to nuclear factor kappa-light-chain-enhancer of activated B cell (NFkappaB) activation. Cells were injected into the murine distal femoral bone marrow cavity. MSC viability and bone formation were examined in vivo. Cytokine secretion was determined in a femoral explant organ culture model.RESULTS: The reporter MSCs survived up to 4 weeks post-implantation. No difference in the number of viable cells was found between high (2.5 * 106) and low (0.5 * 106) cell-injected groups. Injection of 2.5 * 106 reporter MSCs increased local bone mineral density at 4 weeks post-implantation. Injection of 0.5 * 106 constitutive IL-4 or NFkappaB-sensing IL-4-secreting MSCs increased bone mineral density at 2 weeks post-implantation. In the femoral explant organ culture model, LPS treatment induced IL-4 secretion in the NFkappaB-sensing IL-4-secreting MSC group and IL-10 secretion in all the femur samples. No significant differences in tumor necrosis factor (TNF)alpha and IL-1beta secretion were observed between the MSC-transplanted and control groups in the explant culture.DISCUSSION: Transplanted GM MSCs demonstrated prolonged cell viability when transplanted to a compatible niche within the bone marrow cavity. GM IL-4-secreting MSCs may have great potential to enhance bone regeneration in disorders associated with chronic inflammation.
View details for PubMedID 30077567
Diagnosis and treatment of osteochondritis dissecans of the humeral capitellum.
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association
2018; 23 (2): 213–19
Osteochondritis dissecans (OCD) of the humeral capitellum is a critical elbow injury in adolescent overhead throwing athletes. However, its etiology remains unknown. Medical examinations using ultrasonography found that the prevalence of capitellar OCD among adolescent baseball players was approximately from 1% to 3%. A plain anteroposterior radiograph with the elbow in 45° of flexion is essential for the diagnosis of an OCD lesion. The stability of OCD lesions is evaluated on plain radiographs, computed tomography, and magnetic resonance imaging (MRI). Imaging features of the unstable lesions are an epiphyseal closure of the capitellum or a lateral epicondyle, a displaced fragment, or irregular contours of the articular surface and a high signal interface on T2-weighted MRI. A stable lesion has the potential to be healed with conservative treatment. By contrast, surgical treatment should be considered if there is no radiographic improvement within 3 months. In addition, surgery should be performed for the lesions that cause pain during daily activities, have a locking phenomenon, or which are assessed by imaging as obviously unstable. Arthroscopic debridement/loose body removal can be performed for small lesions (≤12 mm in diameter). For large lesions (>12 mm), preservation and/or reconstruction of the articular surface should be selected, such as bone-peg fixation of the lateral part of the fragment and osteochondral autograft transplantation (OAT) from the knee. In the future directions, there is no comparative study of OAT from the knee and rib. In addition, little is known about its long-term outcome, or resulting osteoarthritis. A recent meta-analysis showed that grafts harvested from the knee may lead to donor site morbidity (7.8%). Thus, a novel cartilage tissue engineering approach is anticipated.
View details for DOI 10.1016/j.jos.2017.11.013
View details for PubMedID 29276039
Outcome of conservative treatment for Little League shoulder in young baseball players: factors related to incomplete return to baseball and recurrence of pain.
Journal of shoulder and elbow surgery
2018; 27 (1): 1–9
The purpose of this study was to investigate the factors associated with poor results and pain recurrence in young baseball players with Little League shoulder (LLS).Eighty-seven young baseball players with LLS (mean age, 12.1 years) underwent conservative treatment. Of the players, 68 (78%) underwent conservative treatment involving the prohibition of throwing for an average of 1.2 months whereas the remaining 19 (22%) continued throwing with limitations. We analyzed the factors associated with poor results at 2 months and pain recurrence.At 2 months, 18% of participants reported the presence of pain, and the results regarding the return to baseball were as follows: complete return in 43%, incomplete return in 33%, and no return in 24%. A total of 83 subjects (95%) had completely returned at an average of 2.8 months. Pain recurrence was present in 20 subjects (25%) at an average of 6.2 months. Statistical analysis showed that the following factors were significantly associated with poor results at 2 months: longer period from initial presentation to throwing prohibition and worse shoulder flexibility (P = .04 and P = .01, respectively). It also revealed that the following factors were significantly associated with pain recurrence: higher frequency of pain at 2 months and longer duration until complete return (P = .0003 and P = .04, respectively).It is important for subjects with LLS to be prohibited from throwing immediately after initial presentation. Good shoulder flexibility was associated with a return to baseball without pain. A complete return in subjects who had pain at 2 months was significantly delayed, and these subjects exhibited more rapidly recurring pain after their return.
View details for DOI 10.1016/j.jse.2017.08.018
View details for PubMedID 29054382
Danger of frustrated sensors: Role of Toll-like receptors and NOD-like receptors in aseptic and septic inflammations around total hip replacements
JOURNAL OF ORTHOPAEDIC TRANSLATION
2017; 10: 68–85
The innate immune sensors, Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), can recognize not only exogenous pathogen-associated molecular patterns (PAMPs), but also endogenous molecules created upon tissue injury, sterile inflammation, and degeneration. Endogenous ligands are called damage-associated molecular patterns (DAMPs), and include endogenous molecules released from activated and necrotic cells as well as damaged extracellular matrix. TLRs and NLRs can interact with various ligands derived from PAMPs and DAMPs, leading to activation and/or modulation of intracellular signalling pathways. Intensive research on the innate immune sensors, TLRs and NLRs, has brought new insights into the pathogenesis of not only various infectious and rheumatic diseases, but also aseptic foreign body granuloma and septic inflammation of failed total hip replacements (THRs). In this review, recent knowledge is summarized on the innate immune system, including TLRs and NLRs and their danger signals, with special reference to their possible role in the adverse local host response to THRs.
View details for PubMedID 29130033
Comparison of the Effects of Osteochondral Autograft Transplantation With Platelet-Rich Plasma or Platelet-Rich Fibrin on Osteochondral Defects in a Rabbit Model.
The American journal of sports medicine
2017; 45 (14): 3280–88
Although osteochondral autograft transplantation (OAT) provides satisfactory outcomes for osteochondral defects, for large defects OAT is often inadequate because of graft availability. Osteochondral allograft transplantation is an alternative treatment for large defects, but this approach is limited by graft storage constraints and carries disease transmission risks. Platelet-rich fibrin (PRF) is a second-generation platelet concentrate, and its positive effect on articular cartilage has been reported. However, the effect of PRF with OAT of osteochondral defects is unknown.To compare the effects of OAT with platelet-rich plasma (PRP) and PRF on osteochondral defects in a rabbit model.Controlled laboratory study.Forty-two juvenile rabbits were divided into control, PRP, and PRF groups. In the control and PRP groups, a cylindrical osteochondral defect (5 mm in diameter and 2 mm in depth) was created on the patellar groove, and an osteochondral graft (3.5 mm in diameter and 5 mm in length) harvested from the contralateral side was inserted into the distal portion of the defect. After wound closure, either normal saline or PRP was injected in the knee. In the PRF group, a PRF clot was placed in the defect before grafting. The surgical site was macroscopically and histologically assessed after 3 and 12 weeks.At 3 weeks, the PRF group (n = 8) was macroscopically healed compared with the other 2 groups (control, n = 7; PRP, n = 6) ( P < .005). Histologically, osteochondral graft cartilage of the PRF group had normal cellularity and higher amounts of safranin O staining relative to the other 2 groups ( P < .005). At 12 weeks, all 3 groups (n = 8 per group) were macroscopically healed with normal or nearly normal cartilage, and osteochondral graft cartilage was histologically hyaline cartilage. In contrast, the PRF group healed with hyaline-like cartilage at nongrafted defects, whereas the other 2 groups healed with fibrocartilage ( P < .001).OAT with PRF maintained hyaline cartilage, and the nongrafted defect healed with hyaline-like cartilage.PRF has the potential to improve clinical outcomes of OAT used to treat osteochondral lesions.
View details for DOI 10.1177/0363546517721188
View details for PubMedID 28853913
Ultrasonographic Assessment of the Flexor Pollicis Longus Tendon After Plate Fixation.
2017; 40 (1): e104–e108
Rupture of the flexor pollicis longus tendon is a major complication after volar locking plate fixation of distal radius fracture. This study used ultrasonography to assess the flexor pollicis longus tendon and intermediate tissue. The study assessed 27 patients (28 wrists) who underwent removal of the volar locking plate. Before plate removal, radiography and ultrasonography were performed to assess the relation between the flexor pollicis longus tendon and the volar locking plate. Intraoperatively, the authors evaluated the intermediate tissues between the flexor pollicis longus tendon and the distal volar margin of the plate. Preoperative and intraoperative findings were compared. Intraoperative findings were strongly related to the distance between the flexor pollicis longus tendon and the volar locking plate on ultrasonography. The sensitivity of ultrasonography in detecting thin, membrane-like intermediate tissue through which the plate was visible was 95%, and the specificity was 89% if the distance between the flexor pollicis longus tendon and the plate was less than 0.7 mm. Compression of the flexor pollicis longus tendon was seen in 11 cases (39.3%), and this finding suggested the presence of thin, membrane-like intermediate tissue. The study results showed that ultrasonography could be used to identify the type of intermediate tissue between the flexor pollicis longus tendon and the volar locking plate. [Orthopedics. 2017; 40(1):e104-e108.].
View details for DOI 10.3928/01477447-20161017-01
View details for PubMedID 27783838
Treatment for Ulnar Neuritis Around the Elbow in Adolescent Baseball Players: Factors Associated With Poor Outcome.
The American journal of sports medicine
2017; 45 (4): 803–9
Ulnar neuritis around the elbow is one of the injuries seen in throwing athletes. Outcomes of nonsurgical treatment and factors associated with failure outcomes have not been reported.To investigate the outcomes of treatments for ulnar neuritis in adolescent baseball players.Case series; Level of evidence, 4.We assessed 40 male baseball players with a mean age of 15.0 years (range, 13-17 years) who presented with ulnar neuritis. There were 19 pitchers and 21 fielders whose throwing side was affected. All patients had elbow pain, and 13 patients had hand numbness on the ulnar side. The mean Kerlan-Jobe Orthopaedic Clinic (KJOC) overhead athlete shoulder and elbow score was 52.5 at the first follow-up visit (n = 36 patients). Thirteen patients were identified with ulnar nerve subluxation, and 23 patients had concomitant elbow ulnar collateral ligament (UCL) injury. All patients underwent nonsurgical treatment, which included rehabilitation exercises and prohibition of throwing. If the nonsurgical treatment failed, we recommended surgical treatment. We investigated the outcomes of the nonsurgical and surgical treatments. Return to sports was evaluated, combined with factors associated with return to sports in nonsurgical treatment by univariate and multivariate statistical analysis.The mean follow-up period was 23.6 months (range, 6-39 months). After nonsurgical treatment, 24 patients (60%) returned to the previous competition level after a mean of 2.4 months. Two patients returned to a recreational level. One patient gave up playing baseball at 2 months. The remaining 13 patients underwent surgery and returned to sports after a mean of 2.0 months postoperatively, and 12 had no limitation of sports activities. Multivariate logistical regression analysis demonstrated that hand numbness, ulnar nerve subluxation, and UCL injury were associated with failure of nonsurgical treatment ( P < .05). In addition, KJOC score of <45 at the first follow-up tended to be associated with poor outcomes of nonsurgical treatment ( P = .06).Hand numbness on the ulnar side, ulnar nerve subluxation, and UCL injury are strong predictors of poor outcomes after nonsurgical treatment for ulnar neuritis, and surgery provides excellent results.
View details for DOI 10.1177/0363546516675169
View details for PubMedID 27940806
Bone-peg grafting for osteochondritis dissecans of the humeral capitellum.
Journal of orthopaedic surgery (Hong Kong)
2016; 24 (1): 51–56
To review the outcome of bone-peg grafting for osteochondritis dissecans (OCD) grade II lesions of the humeral capitellum.Records of 10 male adolescent baseball players aged 10 to 15 (mean, 12.3) years who underwent bone-peg grafting for OCD grade II lesions of the humeral capitellum of the dominant arm were reviewed. The mean time from symptom onset to presentation was 11 (range, 1-36) months. The mean duration of conservative treatment was 5 (range, 1-25) months. The mean time from symptom onset to surgery was 17 (range, 3-39) months; it was >6 months in 6 patients. The mean size of the lesions was 13x14 mm. Patients were assessed for elbow pain, range of elbow and forearm motion, Timmerman- Andrews elbow score, return to sports activity level, and radiographic evidence of healing, osteoarthritic changes, and radial head hypertrophy.The mean follow-up period was 25 (range, 10-52) months. Postoperatively, elbow pain was absent in 6, mild in 2, and moderate in 2 patients. The mean range of elbow motion changed from 136º to 139° (p=0.80). The mean Timmerman-Andrews elbow score improved from 163 to 189 (p=0.014); it was excellent in 7, good in 2, and fair in one patient. The mean extent of lesion healing was 71% (range, 33-100%). Five patients achieved complete healing after a mean of 5.2 (range, 5-6) months and returned to sports at a competitive level. The other 5 achieved partial healing of 33 to 56% (mean, 41%) that occurred laterally but not medially. Two of them returned to sports at a competitive level: one changed the throwing side and another had radial head hypertrophy. The remaining 3 underwent arthroscopic debridement of the unhealed lesion at 5, 10, and 15 months. One patient developed secondary osteoarthritis and further underwent costal osteochondral autografting 10 months later. None of the 5 patients with partial healing versus 4 of the 5 patients with complete healing underwent surgery within 6 months of symptom onset. All 3 patients with a dot at the interface versus 2 of the 6 patients with a line at the interface between the fragment and the lesion on MRI had complete healing.Bone-peg grafting is a viable option for OCD grade II lesions of the humeral capitellum when performed within 6 months of symptom onset and when the interface between the fragment and the lesion appears as a dot (rather than a line) on MRI.
View details for DOI 10.1177/230949901602400113
View details for PubMedID 27122513
Complications of Distal Radius Fractures Treated by Volar Locking Plate Fixation.
2016; 39 (5): e893–6
The current study investigated the incidence of complications after surgery for distal radial fractures. This multicenter retrospective study was conducted at 11 institutions. A total of 824 patients who had distal radius fractures that were treated surgically between January 2010 and August 2012 were identified. The study patients were older than 18 years and were observed for at least 12 weeks after surgery for distal radius fractures with a volar locking plate. Sex, age, fracture type according to AO classification, implants, wrist range of motion, grip strength, fracture consolidation rate, and complications were studied. Analysis included 694 patients, including 529 women and 165 men, with a mean age of 64 years. The mean follow-up period was 27 weeks. The fracture consolidation rate was 100%. There were 52 complications (7.5%), including 18 cases of carpal tunnel syndrome, 12 cases of peripheral nerve palsy, 8 cases of trigger digit, 4 cases of tendon rupture (none of the flexor pollicis longus), and 10 others. There was no rupture of the flexor pollicis longus tendon because careful attention was paid to the relationship between the implant and the tendon. Peripheral nerve palsy may have been caused by intraoperative traction in 7 cases, temporary fixation by percutaneous Kirschner wires in 3 cases, and axillary nerve block in 1 case; 1 case appeared to be idiopathic. Tendon ruptures were mainly caused by mechanical stress. [Orthopedics.2016; 39(5):e893-e896.].
View details for DOI 10.3928/01477447-20160517-05
View details for PubMedID 27220118
Outcomes of an open autologous osteochondral plug graft for capitellar osteochondritis dissecans: time to return to sports.
The American journal of sports medicine
2014; 42 (9): 2122–27
Autologous osteochondral plug grafts have been used for capitellar osteochondritis dissecans (OCD), and good clinical results have been described. However, little is known about the optimal timing of return to sports.To investigate the clinical outcomes of open autologous osteochondral plug grafts for capitellar OCD and to address the timing of return to sports.Case series; Level of evidence, 4.Thirty-three male patients with a mean age at the time of surgery of 13.6 years (range, 11-17 years) and with advanced lesions of capitellar OCD underwent a procedure using open autologous osteochondral plug grafts. All patients played baseball, and the lesion affected their throwing side. Thirteen lesions were arthroscopically classified as International Cartilage Repair Society (ICRS) OCD III and 20 lesions as ICRS OCD IV. The mean size of the lesions (sagittal × coronal) was 16 × 14 mm. One to 3 osteochondral plug grafts, with a mean diameter of 7 mm (range, 5-9 mm), were harvested from the lateral femoral condyle and transplanted to the defects. Patients were allowed to begin throwing after 3 months and to return to sports after 6 months. The mean follow-up was 28.4 months (range, 12-76 months), during which elbow pain, Timmerman and Andrews scores, return to sports, and radiographs were evaluated.After surgery, 30 patients (91%) had no elbow pain, and 3 patients (9%) had occasional mild throwing pain. The mean total arc of elbow motion increased significantly from 116° to 133° (P < .05). The mean Timmerman and Andrews score improved significantly from 143 to 190 (P < .05). All except 2 patients returned to a competitive level at which they had previously played after a mean of 6.9 months (range, 6-14 months). One patient chose another sport, and another retired from baseball after high school graduation. All patients achieved graft incorporation, and there was no postoperative enlargement of osteophytes on radiographs. One patient had mild anterior knee pain at the donor site during exercise. The remaining patients had no knee pain. The mean Lysholm score was 99.8.The results of this study indicate that an open autologous osteochondral plug graft allows a return to the previous competitive level of throwing by a mean of 7 months postoperatively.
View details for DOI 10.1177/0363546514538759
View details for PubMedID 24950681
Assessment of medial elbow laxity by gravity stress radiography: comparison of valgus stress radiography with gravity and a Telos stress device.
Journal of shoulder and elbow surgery
2014; 23 (4): 561–66
Valgus instability was reported to be higher with the elbow in 60° of flexion, rather than in 30° of flexion, although there are no studies using valgus stress radiography by gravity (gravity radiography) with the elbow in 60° of flexion.Fifty-seven patients with medial elbow pain participated. For both elbows, valgus stress radiography by use of a Telos device (Telos radiography) and gravity radiography, with the elbow in 60° of flexion, were performed for the assessment of medial elbow laxity. In both radiographs, the medial elbow joint space (MJS) on the affected side was compared with that on the opposite side, and the increase in the MJS on the affected side was assessed.For the Telos radiographs, the mean MJS was 4.7 mm on the affected side and 4.0 mm on the opposite side, with the mean increase in the MJS on the affected side being 0.7 mm. For the gravity radiographs, the mean MJS was 5.0 mm on the affected side and 4.2 mm on the opposite side, with the mean increase in the MJS on the affected side being 0.8 mm. There were significant correlations between the Telos and gravity radiographs in the MJS on the affected side, the MJS on the opposite side, and the increase in the MJS on the affected side (respectively, P < .0001). There was also a high level of intraobserver and interobserver reliability for the assessment of the gravity radiographs.Gravity radiography is useful for assessment of medial elbow laxity, similar to Telos radiography.
View details for DOI 10.1016/j.jse.2014.01.002
View details for PubMedID 24630547
Characteristics and prognosis of medial epicondylar fragmentation of the humerus in male junior tennis players.
Journal of shoulder and elbow surgery
2014; 23 (10): 1514–20
Although medial epicondylar fragmentation of the humerus is a reported elbow injury in junior tennis players, there have been only a few studies on this entity, and none have investigated the characteristics and prognosis of medial epicondylar fragmentation.Forty-one male junior tennis players, aged 11 to 14 years (mean, 13 years), underwent elbow examination by ultrasonography. Elbow re-examination was performed in subjects with medial epicondylar fragmentation at an average of 20 months (12-30 months) after the initial examination.On examination, 9 subjects (22%) had elbow pain. Ultrasonography showed that 6 subjects (15%) had medial epicondylar fragmentation, all of whom had elbow pain. Medial epicondylar fragmentation was present in 5 (38%) of 13 subjects aged 11 to 12 years and in 1 (4%) of 28 aged 13 to 14 years. More subjects aged 11 to 12 years had medial epicondylar fragmentation (P = .0084). All 6 subjects with medial epicondylar fragmentation continued to play tennis between the initial elbow examination and the re-examination. At re-examination, although ultrasonography showed that 5 developed bone union and 1 had nonunion, 3 subjects (50%) reported elbow pain.Our results demonstrated that subjects aged 11 to 12 years had a high frequency (38%) of medial epicondylar fragmentation. Although medial epicondylar fragmentation was the main cause of elbow pain (67%) at the initial elbow examination, all 6 players with medial epicondylar fragmentation continued to play tennis between the initial elbow examination and the re-examination. At re-examination, 5 subjects presented spontaneous bone union (83%), but 3 subjects (50%) reported elbow pain.
View details for DOI 10.1016/j.jse.2014.06.044
View details for PubMedID 25220198
Preoperative imaging criteria for unstable osteochondritis dissecans of the capitellum.
Clinical orthopaedics and related research
2013; 471 (4): 1137–43
The stability of an osteochondritis dissecans (OCD) lesion of the humeral capitellum may be determined by intraoperative probing with unstable lesions being displaceable. Although preoperative imaging is used to diagnose and determine treatment of these lesions, it is unclear whether unstable lesions on imaging correspond to those found intraoperatively.We therefore examined the concordance between preoperative imaging and intraoperative instability and examined the imaging features of the patients who healed without surgery.We retrospectively reviewed 61 patients who underwent OCD of the humeral capitellum surgery or nonoperative treatment. All patients had plain radiography, MRI, and/or CT scans. The presence or absence of stability was determined intraoperatively by the International Cartilage Repair Society OCD classification. We determined the sensitivity, specificity, and predictive value of various imaging findings to predict instability.The following preoperative imaging features were associated with intraoperative instability: a displaced fragment, epiphyseal closure of the capitellum, or a lateral epicondyle observed on radiographs; irregular contours of the articular surface or a high signal interface on T2-weighted MRI; and a displaced fragment observed on CT. Unstable lesions were more common when the epiphysis of the capitellum was closed. Intralesional segmentation was sensitive for detecting an unstable lesion, whereas displaced type on the radiographs and displaced fragment on the CT were specific. The following imaging findings were not seen in nonoperative patients: displaced type and closure of the epiphyseal line on radiographs, irregular contours of the articular surface, articular defects, and T2 high signal intensity interface between the fragments and their bed on the MRI or a displaced fragment on the CT.Although we found high sensitivity for some preoperative findings on imaging, none reached 100% of sensitivity. Preoperative MRI related to the intraoperative assessment of stability.Level III, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.
View details for DOI 10.1007/s11999-012-2462-9
View details for PubMedID 22773394
View details for PubMedCentralID PMC3586018
Radiographic features of Kirner's deformity.
2013; 53 (2): 78–82
We conducted a study of Kirner's deformity to investigate its radiologic features and consider its possible causes. Sixty-seven patients with Kirner's deformity, 41 in our series and 26 retrieved in a survey of the literature were investigated. We divided Kirner's deformity into three types according to the site of curvature: the epiphyseal line, diaphysis, and distal tip. Among our series, 12 hands were affected in males and 26 in females. The gender of the patients for the other three hands was unknown. Twelve cases occurred on the right side, five on the left side, and 24 on both sides. Radiographic data for 34 hands were available. The palmar surface of the distal phalanx was at a mean angle of 27.4 degrees to the long axis of the middle phalanx. Epiphyseal line curvature was seen in four hands (mean patient age, 11 years), diaphysis curvature in 10 (mean age, 12.4 years), and distal tip curvature in 20 (mean age, 26.5 years). Dorsal subluxation of the distal phalanx was noticed in six hands (18%). Radiographic data for 26 hands reported previously were analyzable. The differences between epiphyseal line or diaphysis curvature and distal tip curvature in terms of age were significant in both the present study and the literature.
View details for DOI 10.1111/cga.12010
View details for PubMedID 23751041
Snapping elbow with congenital radial head dislocation: case report.
The Journal of hand surgery
2010; 35 (6): 981–85
An 11-year-old boy with congenital radial head dislocation experienced painful snapping of his left elbow upon movement. He had no previous history of trauma. A plain radiograph of his left elbow showed anterior dislocation of the radial head and flexion deformity of the hypoplastic radial neck. Arthroscopy showed that the snapping of the elbow occurred between the annular ligament and the dislocated radial head during elbow flexion and extension. After the annular ligament was released, the snapping immediately disappeared. Five years after the surgery, the patient has no pain or snapping upon elbow movement.
View details for DOI 10.1016/j.jhsa.2010.02.026
View details for PubMedID 20456870
De Quervain disease caused by abductor pollicis longus tenosynovitis: a report of three cases.
Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand
2009; 14 (1): 43–47
De Quervain disease is caused by a stenosing tenosynovitis in the first dorsal compartment, and the main aetiology is extensor pollicis brevis (EPB) tenosynovitis. We encountered three cases in which EPB tenosynovitis was absent and abductor pollicis longus (APL) tenosynovitis was confirmed during operation. In the treatment of de Quervain disease, APL tenosynovitis should be paid as much attention as EPB tenosynovitis.
View details for DOI 10.1142/S0218810409004220
View details for PubMedID 19598322