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The treatment of patients with femoral head fractures with regard to fixation versus excision is controversial. This study aimed to compare the results of fixation and excision in hip arthroscopy–assisted surgery. This retrospective study included adult patients with femoral head fractures who were treated with hip arthroscopy surgery from March 2016 to April 2020, with a minimum follow-up of 24 months. The patients were divided into two groups: Group 1 (fixation group) and Group 2 (excision group). To compare the therapeutic effects between the two groups, clinical and radiographic outcomes, operative time, pain score, length of hospital stay after surgery and related complications were investigated. There were 13 (mean duration, 47.5 months; range, 24–72 months) and 8 (mean duration, 48.6 months; range, 26–74 months) patients in the fixation and excision groups, respectively. The excision group had better functional results than the fixation group in terms of the median modified Harris hip score (P = 0.009). No significant differences were observed in operative time, pain score or hospital stay after surgery between the two groups. Further, no osteonecrosis of the femoral head or traumatic arthritis occurred in either group. A piece of fracture fragment >2 cm can be considered for hip arthroscopy–assisted internal fixation, whereas the others can be removed. The excision group had better outcomes than the fixation group. Hence, hip arthroscopy–assisted internal fixation or excision of bony fragments led to satisfactory short-term clinical and radiological results for the treatment of Pipkin Type I and II femoral head fractures.

Extracorporeal shockwave therapy (ESWT) and adipose-derived mesenchymal stem cells (ADSCs) have been used clinically for the treatment of osteonecrosis of the femoral head (ONFH). The study elucidated that ESWT, ADSCs, and combination therapy modulated pro-inflammatory cytokines in the articular cartilage and subchondral bone of early rat ONFH.ESWT and ADSCs were prepared and isolated for treatment. Micro-CT, pathological analysis, and immunohistochemistry were performed and analysed.After treatments, subchondral bone of ONFH was improved in trabecular bone volume (BV/TV) (P0.001), thickness (Tb.Th) (P0.01 and 0.001), and separation (Tb.Sp) (P0.001) and bone mineral density (BMD) (P0.001) using micro-CT analysis. The articular cartilage was protected and decreased apoptosis markers after all the treatments. The expression of IL33 (P0.001), IL5 (P0.001), IL6 (P0.001), and IL17A (P0.01) was significantly decreased in the ESWT, ADSCs, and Combination groups as compared with ONFH group. The IL33 receptor ST2 was significantly increased after treatment (P0.001) as compared with ONFH group. The Combination group (P0.01) decreased the expression of IL6 better than the ESWT and ADSCs groups.ESWT, ADSCs and combination therapy significantly protected articular cartilage and subchondral bone of early rat ONFH by modulating the expression of pro-inflammatory cytokines including, IL33 and its receptor ST2, IL5, IL6, and IL17A.

Pipkin type IV femoral head (FH) fracture–dislocations are usually treated via open surgery. There are many surgical approaches for the treatment of this difficult fracture depending on the fracture pattern. Obesity presents another challenging problem in surgical treatment and sometimes leads to a poorer outcome. We discuss herein a patient of a high body mass index (BMI) with a Pipkin type IV FH fracture who underwent open reduction internal fixation (ORIF) of anacetabular fracture with reconstruction plates and hip arthroscopy-assisted fixation of the FH fracture with two Herbert screws via the posterior approach. The intra-articular osteochondral loose bodies were excised by hip arthroscopy simultaneously. The joint congruency and screw positions were checked during surgery by arthroscopy. After 6 months, clinical and computed tomography (CT) follow-ups showed excellent results. The patient of a high BMI recovered immediately and had a satisfactory short-term outcome after hip arthroscopy-assisted surgery. We concluded that hip arthroscopy-assisted surgery is a viable option for the treatment of Pipkin type IV FH fracture–dislocations.

Our study compared the effects of extracorporeal shockwave therapy (ESWT) on the subchondral bone and the articular cartilage in the treatment of early osteoarthritis (OA) of rat knee. The rats were divided into 5 groups which included Sham group, Meniscus group (ESWT applied on medial meniscus), OA group (arthrotomy and medial menisectomy (MMx) and anterior cruciate ligament transection (ACLT), T(M) group (arthrotomy and MMx and ACLT followed by ESWT on medial tibial subchondral bone) and Articular cartilage group (arthrotomy and MMx and ACLT followed by ESWT on medial articular cartilage). Evaluations included the pathological changes of the synovium, articular cartilage and subchondral bone, and compared with ESWT on the meniscus, medial tibial subchondral bone and articular cartilage. The ESWT (0.25 mJ/mm² and 800 impulses) did not cause any damages on the cartilage of the meniscus and the tissue of the joint when compared with Sham group. Among the treatment of osteoarthritic groups (OA, T(M) and Articular cartilage groups), T(M) group showed significant in pathological examination, micro-CT analysis, cartilage grading score and grading of synovium changes by compared with OA and Articular cartilage groups (P < 0.05) in the treatment of early OA knee. In immunohistochemical analysis, T(M) group significantly increased the expression of TGF-β1 but reduced DMP-1, MMP-13 and ADAMTS-5 in the cartilage by compared with OA group and Articular cartilage group (P < 0.05). Our results showed that subchondral bone was an excellent target than articular cartilage for ESWT on early knee osteoarthritis.

Adipose-derived mesenchymal stem cells (ADSCs) and shockwave (SW) therapy have been shown to exert a chondroprotective effect for osteoarthritis (OA). The results of this study demonstrated that autologous ADSCs had dose-dependent and synergistic effects with SW therapy (0.25 mJ/mm2 with 800 impulses) in OA rat knee joint. Autologous, high-dose 2 × 106 ADSCs (ADSC2 group) combined with SW therapy significantly increased the bone volume, trabecular thickness, and trabecular number among in the treatment groups. ADSC2 combined with SW therapy significantly reduced the synovitis score and OARSI score in comparison with other treatments. In the analysis of inflammation-induced extracellular matrix factors of the articular cartilage in OA, the results displayed that ADSC2 combined with SW therapy had a greater than other treatments in terms of reducing tumor necrosis factor-inducible gene (TSG)-6 and proteoglycan (PRG)-4, in addition to increasing tissue inhibitor matrix metalloproteinase (TIMP)-1 and type II collagen. Furthermore, ADSC2 combined with SW therapy significantly reduced the expression of inflammation-induced bone morphogenetic protein (BMP)-2 and BMP-6. Therefore, the results demonstrated that ADSC2 combined with SW therapy had a synergistic effect to ameliorate osteoarthritic pathological factors in OA joints.

Avascular necrosis (AVN) of the femoral head (AVNFH) is a disease caused by injury to the blood supply of the femoral head, resulting in a collapse with osteonecrosis and damage to the articular cartilage. Extracorporeal shockwave therapy (ESWT) has been demonstrated to improve AVNFH owing to its anti-inflammation activity, angiogenesis effect, and tissue regeneration in clinical treatment. However, there are still so many pieces of the jigsaw that need to be fit into place in order to ascertain the mechanism of ESWT for the treatment of AVNFH. The study demonstrated that ESWT significantly protected the trabecular bone volume fraction BV/TV ( P < 0.01 ) and the trabecular thickness ( P < 0.001 ), while in contrast, the trabecular number and trabecular separation were not significantly different after treatment as compared with AVNFH. ESWT protected the articular cartilage in animal model of AVNFH. The levels of IL1-β and IL33 were significantly induced in the AVNFH group ( P < 0.001 ) as compared with Sham and ESWT groups and reduced in ESWT group ( P < 0.001 ) as compared with AVNFH group. In addition, the expression of the receptor of IL33, ST2, was reduced in AVNFH and induced after ESWT ( P < 0.001 ). The expression of IL17A was induced in the AVNFH group ( P < 0.001 ) and reduced in the ESWT group ( P < 0.001 ). Further, the expression of the receptor of IL17A, IL17RA, was reduced in the AVNFH group ( P < 0.001 ) and improved to a normal level in the ESWT group as compared with Sham group ( P < 0.001 ). Taken together, the results of the study indicated that ESWT modulated the expression of IL1-β, pro-inflammatory cytokines IL33 and IL17A, and their receptors ST2 and IL17RA, to protect against loss of the extracellular matrix in the articular cartilage of early AVNFH.

Osteoporosis (OP) causes bone loss and weakness, increasing the risk of bone fracture. In this study, rats were divided into Sham, OP, SW(F) (0.25 mJ/mm2 with 1600 impulses to the left medial femur), and SW(T) (0.25 mJ/mm2 with 1600 impulses to the left medial tibia). The bone strength results following SW(T) were better than SW(F) in the modulus, extension at peak load, handleability, and strain at break. SW(T) had the best prevention for bone loss in both lower limbs of ovariectomized (OVX) rats. The cartilage cellular matrixes of both knees were improved in SW(T) and SW(F) compared to that of OP. Serum bone morphogenetic protein 2 (BMP2) in rats undergoing SW(T) or SW(F) was significantly improved compared to that in Sham and OP. The expressions of BMP2, BMP4, and SMAD family member 4 (Smad4) in addition to the Wnt family member 3A (Wnt3a) and Cyclin D1 signaling key factors were significantly induced in the cartilage of both knees by shockwave (SW). SW(T) presented the best efficacy to induce serum BMP2 to prevent bone loss from both lower limbs. Here, we display the protective effects of SW therapy to induce BMP2, BMP4, Smad4, Wnt3a, and Cyclin D1 signaling factors for cartilage loss in both knees of OVX rats.

BackgroundAcromioclavicular joint (ACJ) dislocation is a relatively common shoulder injury. For the treatment of cases of severe ACJ dislocation (Rockwood type III–V), hook plate fixation is an easy-to-master and minimally-invasive approach to surgical intervention. Over stress on the acromion following hook plate fixation often leads to acromial complications such as osteolysis and loss of reduction. We hypothesized that suspensory reconstruction alongside hook plate fixation might provide a superior stability and reduce complications as compared with hook plate fixation alone. The purpose of the study was to assess the clinical and radiographic outcomes of these two surgical modalities.MethodsWe retrospectively enrolled 49 patients with acute ACJ dislocation from May 2010 to December 2018. Among them, 19 patients received hook plate fixation only (HP group), and 19 underwent concomitant hook plate fixation and loop suspension fixation with two mersilene sutures (HM group). The demographic data of the patients were recorded and analyzed. All patients underwent a shoulder X-ray initially, immediately postoperatively, and at 1, 3, 6 and 12 months to measure the relative coracoclavicular distance (rCCD). Clinical assessment of shoulder function outcome was conducted using the Constant Murley Score (CMS); the University of California at Los Angeles (UCLA) Shoulder Score was also measured at the latest follow-up.ResultsThere were no significant differences in the demographic data between the two groups. With regards to the CMS and the UCLA score, the HM group and HP group both had excellent outcomes, and no significant differences in scores were observed between groups (CMS: 93.90 ± 6.16 versus 94.47 ± 7.26,p = 0.47; UCLA score: 32.84 ± 2.91 versus 34.32 ± 1.16,p = 0.07). However, the HM group demonstrated substantial superiority in terms of maintenance of the rCCD over the HP group (91.47 ± 27.47 versus 100.75 ± 48.70,p = 0.015). In addition, there was less subacromial osteolysis in the HM group than the HP group (52.6% versus 15.8%,p = 0.038).ConclusionBoth fixations yielded excellent functional outcomes. However, concomitant hook plate fixation with loop suspensory reconstruction demonstrated the fewer acromion complications and statistical differences in reduction maintenance with less clinical significance.

The dose-dependent effects of adipose-derived mesenchymal stem cell-conditioned medium (ADSC-CM) were compared with those of shockwave (SW) therapy in the treatment of early osteoarthritis (OA). Anterior cruciate ligament transaction (ACLT) with medial meniscectomy (MMx) was performed in rats divided into sham, OA, SW, CM1 (intra-articular injection of 100 μL ADSC-CM into knee OA), and CM2 (intra-articular injection of 200 μL ADSC-CM) groups. Cartilage grading, grading of synovium changes, and specific molecular analysis by immunohistochemistry staining were performed. The OARSI and synovitis scores of CM2 and SW group were significantly decreased compared with those of the OA group (p &lt, 0.05). The inflammatory markers interleukin 1β, terminal deoxynucleotidyl transferase dUTP nick end labeling and matrix metalloproteinase 13 were significantly reduced in the CM2 group compared to those in the SW and CM1 groups (p &lt, 0.001). Cartilage repair markers (type II collagen and SRY-box transcription factor 9, SOX9) expression were significantly higher in the CM2 group than in the other treatment groups (p &lt, 0.001, p &lt, 0.05). Furthermore, inflammation-induced growth factors such as bone morphogenetic protein 2 (BMP2), BMP5, and BMP6 were significantly reduced in the treatment groups, and the CM2 group showed the best results among the treatments (p &lt, 0.05). In conclusion, ADSC-CM and SW ameliorated the expression of inflammatory cytokines and inflammation-induced BMPs to protect the articular cartilage of the OA joint.

We assessed the pathological changes of articular cartilage and subchondral bone on different locations of the knee after extracorporeal shockwave therapy (ESWT) in early osteoarthritis (OA). Rat knees under OA model by anterior cruciate ligament transaction (ACLT) and medial meniscectomy (MM) to induce OA changes. Among ESWT groups, ESWT were applied to medial (M) femur (F) and tibia (T) condyles was better than medial tibia condyle, medial femur condyle as well as medial and lateral (L) tibia condyles in gross osteoarthritic areas (p T(M+L) > F(M) in OA rat knees.

The goal of our research was demonstrated that multiple molecules in microenvironments of the early osteoarthritis (OA) joint tissue may be actively responded to extracorporeal shockwave therapy (ESWT) treatment, which potentially regulated biological function of chondrocytes and synovial cells in early OA knee. We demonstrated that shockwave treatment induced the expression of protein-disulfide isomerase-associated 3 (Pdia-3) which was a significant mediator of the 1α,25-Dihydroxyvitamin D 3 (1α,25(OH)2D3) rapid signaling pathway, using two-dimensional electrophoresis, histological analysis and quantitative polymerase chain reaction (qPCR). We observed that the expression of Pdia-3 at 2 weeks was significantly higher than that of other group at 4, 8, and 12 weeks post-shockwave treatment in early OA rat knee model. The other factors of the rapid membrane signaling pathway, including extracellular signal-regulated protein kinases 1 (ERK1), osteopontin (OPG), alkaline phosphatase (ALP), and matrix metallopeptidase 13 (MMP13) were examined and were found to be significantly increased at 2 weeks post-shockwave treatment by qPCR in early OA of the knee. Our proteomic data revealed significant Pdia-3 expression in microenvironments of OA joint tissue that could be actively responded to ESWT, which may potentially regulate the biological functions of chondrocytes and osteoblasts in the treatment of the early OA of the knee.

Purpose:Femoral head fracture dislocations are serious articular fractures that are associated with soft tissue injuries and are challenging to treat. Arthroscopic surgery may be a way to treat fracture reduction and fixation, thereby avoiding the need for extensive arthrotomy.Methods:We followed up a consecutive series of seven patients with femoral head fracture dislocation via a scope-assisted percutaneous headless screw fixation between 2016 and 2017. The clinical and radiological results were assessed.Results:The locations of the fracture were all involving infra-foveal area. The mean follow-up duration was 18 (range 12–24) months. The mean Harris hip score was 90.8 (range 88–93) at the latest follow-up. None of the patients showed early osteoarthritis, heterotopic ossification, or avascular necrosis. The average maximal displacement of the fracture site was improved from preoperative 6.79 mm (range 4.21–12.32) to postoperative 2.76 mm (range 0.97–3.97). Concomitant intra-articular hip lesions secondary to traumatic hip dislocation can also be treated.Conclusion:Managing the infra-foveal fracture of the femoral head using arthroscopic reduction and fixation with headless screws can be a safe and minimally invasive option. More patients and longer follow-up are needed for a definite conclusion.

Background VP1 of the chicken anemia virus (CAV) is a structural protein that is required for virus encapsulation. VP1 proteins are present both in the nucleus and cytoplasm; however, the functional nuclear localization signal (NLS) and nuclear export signal (NES) of VP1 are still unknown. This study aimed to characterize the NLS and NES motifs of VP1 using bioinformatics methods and multiple-site fragment deletions, and investigate shuttling of VP2 from nucleus to cytoplasm by co-transfection with VP1. Methods Two putative NLS motifs were predicted by the WoLF PSORT and NLStradamus programs from the amino acid sequence of VP1. Three NES motifs of VP1 were predicted by the NetNES 1.1 Server and ELM server programs. All mutants were created by multiple-site fragment deletion mutagenesis. VP1 and VP2 were co-expressed in cells using plasmid transfection. Results A functional NLS motif was identified at amino acid residues 3 to 10 (RRARRPRG) of VP1. Critical amino acids 3 to 10 were significantly involved in nuclear import in cells and were evaluated using systematic deletion mutagenesis. Three NES motifs of VP1 were predicted by the NetNES 1.1 Server and ELM server programs. A functional NES was identified at amino acid residues 375 to 388 (ELDTNFFTLYVAQ). Leptomycin B (LMB) treatment demonstrated that VP1 export from nucleus to cytoplasm occurred through a chromosome region maintenance 1 (CRM1)-dependent pathway. With co-expression of VP1 and VP2 in cells, we observed that VP1 may transport VP2 from nucleus to cytoplasm. Conclusion Our data showed that VP1 of CAV contained functional NLS and NES motifs that modulated nuclear import and export through a CRM1-dependent pathway. Further, VP1 may play a role in the transport of VP2 from nucleus to cytoplasm.

Background: This study tested the hypothesis that hyperbaric oxygen (HBO) therapy enhanced the circulating levels of endothelial progenitor cells (EPCs), soluble angiogenesis factors, and blood flow in ischemic areas in patients with peripheral arterial occlusive disease (PAOD). Methods: In total, 57 consecutive patients with PAOD undergoing the HBO therapy (3 atmospheres (atm) for 2 h each time) were prospectively enrolled into the present study. Venous blood sampling was performed to assess the circulating levels of EPCs and soluble angiogenesis factors prior to and during five sessions of HBO therapy. Additionally, skin perfusion pressure (SPP), an indicator of blood flow in ischemic areas, was measured by moorVMS-PRES. Results: The results demonstrated that the circulating levels of EPCs (cluster of differentiation (CD)34+/CD133+/CD45dim, CD31+/CD133+/CD45dim, CD34+) and soluble angiogenesis factors&mdash, vascular endothelial growth factor/stromal cell-derived factor 1/hepatocyte growth factor/fibroblast growth factor (VEGF/SDF-1&alpha, /HGF/FGF) were significantly increased post-HBO therapy as compared to pre-HBO therapy (all p &lt, 0.01). Additionally, Matrigel assay showed that the angiogenesis was significantly increased in post-HBO therapy as compared to prior to therapy (p &lt, 0.001). Furthermore, SPP was significantly increased in the ischemic area (i.e., plantar foot and mean SPP of the ischemic foot) in post-HBO therapy as compared to pre-HBO therapy (all p &lt, 0.01). Importantly, the HBO therapy did appear to result in complications, and all the patients were uneventfully discharged without amputation. Conclusions: HBO therapy augmented circulating levels of EPCs and angiogenesis factors, and improved the blood flow in the ischemic area.

Extracorporeal shock wave (ECSW) and adipose-derived mesenchymal stem cells (ADMSCs) have been recognized to have capacities of anti-inflammation and angiogenesis. We tested the hypothesis that ECSW and ADMSC therapy could attenuate ischemia-reperfusion- (IR-) induced thigh injury (femoral artery tightened for 6 h then the tightness was relieved) in rats. Adult male SD rats (n=30) were divided into group 1 (sham-control), group 2 (IR), group 3 (IR + ECSW/120 impulses at 0.12 mJ/mm2 given at 3 h/24 h/72 h after IR), group 4 (allogenic ADMSC/1.2 × 106 cell intramuscular and 1.2 × 106 cell intravenous injections 3 h after IR procedure), and group 5 (ECSW + ADMSC). At day 7 after the IR procedure, the left quadriceps muscle was harvested for studies. At 18 h after the IR procedure, serum myoglobin/creatine phosphokinase (CPK) levels were highest in group 2, lowest in group 1, and with intermediate values significantly progressively reduced in groups 3 to 5 (all p<0.0001). By day 5 after IR, the mechanical paw-withdrawal threshold displayed an opposite pattern of CPK (all p<0.0001). The protein expressions of inflammatory, oxidative-stress, apoptotic, fibrotic, DNA-damaged, and mitochondrial-damaged biomarkers and cellular expressions of inflammatory and DNA-damaged biomarkers exhibited an identical pattern of CPK among the five groups (all p<0.0001). The microscopic findings of endothelial-cell biomarkers and number of arterioles expressed an opposite pattern of CPK, and the angiogenesis marker was significantly progressively increased from groups 1 to 5, whereas the histopathology showed that muscle-damaged/fibrosis/collagen-deposition areas exhibited an identical pattern of CPK among the five groups (all p<0.0001). In conclusion, ECSW-ADMSC therapy is superior to either one applied individually for protecting against IR-induced thigh injury.

This study compared the effects of extracorporeal shock wave therapy (ESWT) and alendronate sodium (alendronate) in osteoarthritis (OA) of rat knees. The control group was subjected to a sham surgery and did not receive either ESWT or alendronate treatment. The OA group underwent anterior cruciate ligament transection (ACLT) and medial meniscectomy (MM) surgery and did not receive either ESWT or alendronate. The ESWT group underwent ACLT and MM surgery and received ESWT after the surgery. The alendronate group received alendronate after ACLT and MM surgery. The evaluations included radiograph, bone mineral density (BMD), serum C-telopeptide collagen II (CTX-II), cartilage oligomeric protein (COMP), alkaline phosphatase and osteocalcin, histopathological examination and immunohistochemical analysis. Radiographs at 12 weeks showed pronounced OA changes in the OA group. The BMD values, CTX-II, COMP, alkaline phosphatase and osteocalcin showed no significant difference between ESWT and alendronate groups. In histopathology, the Mankin and Safranin O scores significantly increased in the OA, ESWT and alendronate groups, but without any significant difference between the ESWT and alendronate groups. In immunohistochemical analysis, the von Willebrand factor (vWF), vascular endothelial factor (VEGF), soluble vascular cell adhesion molecule (sVCAM), proliferating cell nuclear antigen (PCNA), bone morphogenetic protein 2 (BMP-2), and osteocalcin expressions in articular cartilage and subchondral bone showed a significant decrease in the OA group, but no difference was noted between the ESWT and alendronate groups. In conclusion, ESWT and alendronate sodium demonstrate equal protective effects from developing osteoarthritis of the knee in rats.

Background: Shockwave was shown to enhance the healing of anterior cruciate ligament (ACL) reconstruction in rabbits. This study evaluated the effect of extracorporeal shockwave therapy (ESWT) on ACL reconstruction in human subjects. We hypothesized that ESWT may improve human ACL reconstruction. Methods: Fifty-three patients were randomized into two groups with 26 patients in ESWT group and 27 patients in control group. The ESWT group underwent single-bundle hamstring autograft ACL reconstruction and received ESWT immediately after surgery. The control group underwent ACL surgery without ESWT. Both groups received the same rehabilitation postoperatively. The evaluations included Lysholm score, IKDC score and KT-1000, radiograph, bone mineral density, and magnetic resonance imaging. Results: ESWT group showed significantly better Lysholm score than control group at 1 and 2 y postoperatively (P < 0.001 and 0.001, respectively). No significant difference was noted in IKDC score between the two groups (P ¼ 0.080 and 0.076, respectively). The KT-1000 values were significantly better in ESWT group than control group at 2 y postoperatively (P ¼ 0.027). The tibia tunnel on X-ray was significantly smaller in ESWT group compared with control group at 2 y (P ¼ 0.018). The bone mineral density values showed no discernable difference between the two groups at 6 mo and 2 y (P ¼ 0.522 and 0.984, respectively). On magnetic resonance imaging, ESWT group showed significant decrease in tibia tunnel enlargement at 6 mo and 2 y compared with the control group (P ¼ 0.024 and

For recurrent patellar dislocation, reconstruction of the medial patellofemoral ligament (MPFL) with replacement autografts has often been performed but with only little data on the tensile properties of the MPFL to guide graft selection. With its complex anatomy and geometry, these properties are difficult to obtain. In this study, we showed how the orientation of the femur-MPFL-patella complex (FMPC) during uniaxial tensile testing can have a significant effect on its structural properties. Twenty two FMPCs were isolated from porcine stifle joints and randomly assigned to two groups of 11 each. For the first group, the specimens were loaded to failure with the patella oriented 30 degrees away from the direction of the applied load to mimic its orientation in situ, called natural orientation. In the second group, the patella was aligned in the direction of the tensile load, called non-natural orientation. The stiffness for the natural orientation group was 65 ± 13 N/mm, 32% higher than that for the non-natural orientation group (50 ± 17 N/mm; p < 0.05). The ultimate loads were 438 ± 128 N and 386 ± 136 N, respectively (p > 0.05). Ten out of 11 specimens in the natural orientation group failed at the femoral attachment (the narrowest portion of the MPFL) compared to 6 out of 11 in the non-natural orientation group. Our findings suggest that the specimen orientation that mimics the in-situ loading conditions of the MPFL should be used to obtain more representative data for the structural properties of the FMPC.

Dysregulation of cartilage homeostasis and the changes in the density and the architecture of the subchondral bone were postulated as a potent mechanically pathological activity contributing to osteoarthritis (OA) pathogenesis. Extracorporeal shockwave therapy (ESWT) is a new, none invasive and effective method in the treatment of animal OA model. In the current study, we demonstrated that shockwave induced the expression of protein-disulfide isomerase-associated 3 (Pdia-3) which is a multifunctional protein hypothesized to be a significant mediator for 1α,25-Dihydroxyvitamin D3 (1α,25(OH)2D3) signaling pathway using two-dimensional electrophoresis. Histological analysis and quantitative polymerase chain reaction (qPCR) were verified and observed that the expression of Pdia-3 at 2 weeks was significantly higher than that of any other group at 4 weeks, 8 weeks, and 12 weeks post-shockwave treatment in early OA knee of rat. The other factors of the 1α,25(OH)2D3 rapid membrane signaling pathway including extracellular signal-regulated protein kinases 1 (ERK1), osteopontin (OPG), alkaline phosphatase (ALP), and matrix metallopeptidase 13 (MMP13) were measured and significantly increased by qPCR at 2 weeks post-shockwave treatment in early OA knee. Our proteomic data revealed significant Pdia-3 expression in microenvironments of joint tissue that could be actively responded to ESWT, which may potentially regulate biological function of chondrocytes and osteoblasts in the treatment of OA knee.

Extracorporeal shockwave therapy (ESWT) is a new non-invasive method to induce tissue regeneration and repair the damaged osteoarthritis (OA) of knee. Previous studies suggested subchondral bone as the key target for OA treatment. However, the relationship of the effect and different locations of subchondral bone is unknown. The purpose of the study was to investigate whether the subchondral bone of medial tibia as the target for ESWT in early OA knee treatment and compared with various locations on lateral tibia and femur condyles. Application of ESWT on the medial tibial subchondral bone ameliorated 38% in gross pathological OA changes (compared to OA, P < 0.001), 94 % in OARSI score (compared to OA, P < 0.001) and 45% in cartilage defect (compared to OA, P < 0.001), 17% in bone mineral density (compared to OA, P < 0.001) than lateral tibia and femur. In micro-CT analysis, ESWT on medial tibial subchondral bone increased bone volume (61% vs 44% in tibia and 62% vs 53% in femur, P < 0.05), yield stress (6 MPa vs 4 MPa in tibia and 4 MPa vs 2 MPa in femur, P < 0.05) and decreased bone porosity (38% vs 53% in tibia and 37% vs 46% in femur, P < 0.05) than OA. The TUNEL, PCNA and osteocalcin significantly influenced the levels of molecular expression in different locations of ESWT application. Our results confirm that application of ESWT to the medial tibial subchondral bone has more effective therapy for OA knee than lateral locations of joint knee.

Extracorporeal shockwave therapy (ESWT) has shown chondroprotective effects on the initiation of the osteoarthritis (OA) changes of the rat knee. This study evaluated 69 significant expressed profiles of microRNA (miRNA) in the articular cartilage and subchondral bone after ESWT. There were 118 target genes identified for miRNAs of interest in articular cartilage and 214 target genes in subchondral bone by next generation sequencing (NGS). In principal component analysis (PCA), the relationships of miRNA expression in bone and cartilage were improved after ESWT. Global functional annotation showed that predicted targets were involved in cartilage development, inflammatory and immune response, ion binding, angiogenesis, cell adhesion, cell cycle, transcription and translation, gene expression, NTP binding, signal transduction, collagen fibril organization, apoptotic process, chondrocyte differentiation, cell differentiation, bone development as well as cell proliferation. The miRNAs profile and the target genes were comprehensively surveyed and compared in articular cartilage and subchondral bone of early OA knee before and after ESWT. Our study represents the direct assessment to date of miRNA expression profiling in early OA articular cartilage and subchondral bone. The results provide insights that could contribute to the development of new biomarkers and therapeutic strategies for OA changes and the treatment with ESWT.

This study investigated the effect of plasmid cytomegalovirus (pCMV)-bone morphogenetic protein 2 (BMP-2) gene therapy on the healing of the tendon-bone interface after anterior cruciate ligament (ACL) reconstruction in rabbits.The pCMV-BMP-2 was synthesized from full-length human BMP-2 complementary deoxyribonucleic acid, followed by cloning into pCMV Script vector (Clontech Laboratories, Inc., San Jose, CA), and was delivered by a xenogeneic (rat kidney) cell line. The ACL was reconstructed by the transfer of extensor digital tendon in the proximal tibia. In the study group the pCMV-BMP-2 gene-transfected normal rat kidney cells mixed with calcium alginate gel were placed at the tendon-bone interface, whereas no pCMV-BMP-2 was used in the control group. The evaluations included radiography, bone mineral density, magnetic resonance imaging, biomechanical study, histologic examination, and immunohistochemical analysis.Bone mineral density showed no significant difference between the groups (P.05). Magnetic resonance imaging showed significantly better contact between tendon and bone in the study group compared with the control group (P.0001). In the biomechanical study, significantly higher failure load and maximal graft tension were noted in the study group compared with the control group (P = .034). The modes of graft failure were rupture of the tendon proper in 78% and graft pullout from the bone tunnel in 22% of specimens in the study group versus graft rupture in 22% and graft pullout in 78% in the control group (P = .018). On histologic examination, the study group showed significantly better integration between tendon and bone, as well as more bone tissue around the tendon graft, than the control group (P = .0004). On immunohistochemical analysis, the study group showed significantly higher expressions of von Willebrand factor, vascular endothelial growth factor, proliferation cell nuclear antigen, and BMP-2 than the control group (P.05).The pCMV-BMP-2 gene therapy significantly improved the healing of tendon to bone and promoted angiogenesis and osteogenesis at the tendon-bone interface after ACL reconstruction in the rabbit model.Application of pCMV-BMP-2 gene therapy may be an effective adjunct therapy in ACL reconstruction.

Cocktail therapy consists of extracorporeal shock wave treatment (ESWT), hyperbaric oxygen therapy (HBO) and alendronate. We hypothesized that this combined therapy may produce better results than ESWT alone when treating hip necrosis. This prospective, randomized study evaluated the effectiveness of cocktail therapy in early hip necrosis, and then compared it to shock wave treatment alone. Sixty-three patients (98 hips) were randomly divided into two groups. Group A consisted of 28 patients (50 hips) who received cocktail therapy, and group B consisted of 35 patients (48 hips) who received only ESWT. Each affected hip was treated with 6,000 shocks of ESWT at 28 kV (equivalent to 0.62 mJ/mm2) in a single session. Cocktail patients also received HBO therapy performed in a multi-place chamber daily for 20 treatments, and they were administered 70 mg of alendronate orally per week for 1 year. The evaluations included clinical assessment, radiograph and MRI. After a minimum of 2-years of follow-up, the overall results showed 74% improved, 16% unchanged and 10% worsened in group A; and 79.2% improved, 10.4% unchanged and 10.4% worsened in group B (P = 0.717). Total hip replacement (THR) was performed for 10% of group A and 10.4% of group B (P = 0.946). MRI showed significant reduction in bone marrow edema and a trend of decrease in the size of the lesions in both groups, however, no difference was noted between the two groups. Cocktail therapy is effective for early hip necrosis, but the results are comparable to ESWT in short-term follow up. The joint effects of HBO and alendronate over EWST were not observed. Long-term results are needed to determine whether or not the synergistic effects of ESWT, HBO and alendronate over ESWT alone exist in early hip necrosis.

The hypothesis of this study is that anterolateral (A-L) trans-tibia approach is better than anteromedial (A-M) technique in posterior cruciate ligament (PCL) reconstruction. The purpose of this prospective clinical study was to compare the functional outcomes of A-M and A-L trans-tibia approach in arthroscopic PCL reconstruction.Between 1999 and 2003, 55 patients (55 knees) with an average age of 30 +/- 11 years (range 16-60 years) underwent arthroscopic single-bundle reconstruction for symptomatic isolated PCL tear. Patients were randomly divided into two groups with 28 patients (28 knees) undergoing A-M trans-tibia approach on odd-numbered days, and 27 patients (27 knees) with A-L trans-tibia approach on even-numbered days. Hamstring auto grafts were used in all cases. All patients received the same rehabilitation program postoperatively. The evaluation parameters included clinical assessment, functional outcome, ligament laxity and radiographic changes of the affected knee.Significant improvements in pain and function of the knee were observed at an average follow-up of 48 +/- 15.9 months for A-M and 45.0 +/- 13.7 months for A-L approach. However, the difference between the two techniques was statistically not significant. In IKDC for symptom-activity level, normal or nearly normal knees were noted in 68% of A-M and 67% of A-L approach, respectively, but no difference was noted between the two groups. In ligament laxity, approximately two-thirds of the knees showed normal posterior laxity with no difference between the two groups. Radiographs of the knee showed no discernible difference in the overall alignment and degenerative changes as well as the sizes of bone tunnel between the two groups.A-M and A-L trans-tibia arthroscopic PCL reconstructions produced comparable clinical results in short-term follow-up. Contrary to our initial hypothesis, the theoretical disadvantages of A-M technique including graft failure were not observed during the follow-up period. Long-term results are needed to confirm the adverse effects of A-M trans-tibia approach in PCL reconstruction.

Tendon-bone healing is crucial in success of anterior cruciate ligament (ACL) reconstruction surgery. Demineralized bone matrix (DBM) is a physiological component that has the inherent potential of bone regeneration. We hypothesized that the alternative bone substitute can affect the structural properties of tendon graft in tibial tunnel healing. Five 12-week-old New Zealand white rabbits in study group underwent unilateral ACL reconstructions plus the application of 0.5 cc DBM in the tibial tunnel. The assessment included radiological assessment and histologic and immunohistochemical analyses. Radiological examination revealed that DBM group had the least displacement of tendon in tibial tunnel (0.4 ± 0.12; P = 0.03). Histologic examination showed significantly better integration between tendon and bone in DBM group (77.62 ± 2.08; P = 0.001). On immunohistochemical analysis, the DBM group showed significantly higher expressions of bone morphogenetic protein-2 and vascular endothelial growth factor than control group (51.98 ± 3.02, 84.06 ± 1.86; P = 0.001, P < 0.001). DBM enhances the tendon-bone healing in ACL reconstruction. DBM has the potential use in ACL surgery.

The causes of graft failure after anterior cruciate ligament (ACL) reconstruction are multifactorial including the methods of graft fixation. The purpose of this study was to examine the ACL graft failure in three different methods of graft fixations including interference screw fixation, suture-post fixation and combined interference screw and suture-post fixation. We hypothesized that the fixation method after ACL reconstruction can affect the graft healing in tibial tunnel. Eighteen New Zealand white rabbits were categorized into three groups according to the method of fixation in unilateral ACL reconstruction with long digital extensor autograft. Histological examination demonstrated that the combined fixation and suture-post fixation groups showed significantly better integration between tendon and bone (P = 0.04). In immunohistochemical analysis, the combined fixation and suture-post fixation groups showed significantly higher BMP-2 and VEGF expressions than interference screw (P

Ligaments and tendons are dense connective tissues that are important in transmitting forces and facilitate joint articulation in the musculoskeletal system. Their injury frequency is high especially for those that are functional important, like the anterior cruciate ligament (ACL) and medial collateral ligament (MCL) of the knee as well as the glenohumeral ligaments and the rotator cuff tendons of the shoulder. Because the healing responses are different in these ligaments and tendons after injury, the consequences and treatments are tissue- and site-specific. In this review, we will elaborate on the injuries of the knee ligaments as well as using functional tissue engineering (FTE) approaches to improve their healing. Specifically, the ACL of knee has limited capability to heal, and results of non-surgical management of its midsubstance rupture have been poor. Consequently, surgical reconstruction of the ACL is regularly performed to gain knee stability. However, the long-term results are not satisfactory besides the numerous complications accompanied with the surgeries. With the rapid development of FTE, there is a renewed interest in revisiting ACL healing. Approaches such as using growth factors, stem cells and scaffolds have been widely investigated. In this article, the biology of normal and healing ligaments is first reviewed, followed by a discussion on the issues related to the treatment of ACL injuries. Afterwards, current promising FTE methods are presented for the treatment of ligament injuries, including the use of growth factors, gene delivery, and cell therapy with a particular emphasis on the use of ECM bioscaffolds. The challenging areas are listed in the future direction that suggests where collection of energy could be placed in order to restore the injured ligaments and tendons structurally and functionally.

This study investigated the effectiveness of extracorporeal shockwave therapy (ESWT) in osteoporotic (OP) osteoarthritis (OA) of rat knee. Fifty-six rats were divided into seven groups including sham, OA, OP, OA + OP, OA + ESWT, OP + ESWT, and OA + OP + ESWT groups. The evaluations included gross pathology, bone mineral density (BMD), micro-computed tomography (micro-CT) scan, bone-strength test, histopathologic examination, and immunohistochemical analysis. On gross pathology, group OA + OP showed larger areas of osteoarthritic changes than did groups OA and OP, as compared with the sham group. BMD and bone strength significantly decreased in groups OA, OP, and OA + OP relative to the sham group, and ESWT significantly improved BMD and bone-strength changes. On micro-CT scan, the subchondral plate thickness significantly decreased, and the bone porosity increased in groups OA, OP, and OA + OP, and ESWT significantly improved the changes in subchondral-plate thickness and bone porosity. In histopathologic examination, Mankin score and safranin O score significantly increased in groups OA and group OA + OP, but not in group OP relative to the sham group, and ESWT significantly improved the changes. In immunohistochemical analysis, Dickkopf-1 (DKK-1) significantly increased, but vessel endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA), and bone morphogenetic protein 2 (BMP-2) decreased in groups OA, OP, and OA + OP relative to the sham group, and ESWT significantly reversed the changes. Osteoporosis increased the severity of cartilage damage in osteoarthritis of the knee. ESWT showed effectiveness in the reduction of osteoporotic osteoarthritis of the knee in rats.