Medial-pivot total knee arthroplasty enhances tibiofemoral axial rotation stability in weight-bearing mid-range flexion compared to posterior-stabilised system.

PURPOSE: Total knee arthroplasty (TKA) stands as a primary intervention for severe knee ailments, yet concerns remain regarding postoperative patient satisfaction and flexion instability. This study aims to evaluate the in-vivo kinematics of medial-pivot (MP) and posterior-stabilised (PS) designs during step-up activity, in comparison to the kinematics of the nonoperated contralateral knee. METHODS: Sixteen patients with PS-TKA and 14 with MP-TKA were retrospectively examined. Clinical outcomes were assessed using patient-completed questionnaires. Motion during step-up was captured using a dual fluoroscopic system. Statistical analysis was applied to evaluate the in-vivo tibiofemoral six-degree-of-freedom kinematics and articular contact positions between the two groups. RESULTS: Despite being older, patients in the MP group reported higher postoperative subjective scores for weight-bearing functional activities. The axial rotation centres of MP-TKA located on the medial tibial plateau exhibited less variance compared to PS-TKA and contralateral knees. Compared to the contralateral knee (contralateral to medial-pivot [C-MP] or contralateral to posterior-stabilised [C-PS]), the MP group exhibited limited range of motion in terms of anteroposterior translation (MP: 3.6 ± 1.3 mm vs. C-MP: 7.4 ± 2.5 mm, p < 0.01) and axial rotation (MP: 6.6 ± 1.9° vs. C-MP: 10.3 ± 4.9°, p = 0.02), as well as in the PS group for anteroposterior translation (PS: 3.9 ± 1.7 mm vs. C-PS: 7.2 ± 3.7 mm, p < 0.01). CONCLUSION: The MP group with better postoperative ratings demonstrated a more stable MP axial rotation pattern during step-up activity compared to the PS group, underscoring the pivotal role of prosthetic design in optimising postoperative rehabilitation and functional recovery. LEVEL OF EVIDENCE: Level III.

Role of nano-hydrogels coated exosomes in bone tissue repair.

With the development of nanotechnology, nanomaterials are widely applied in different areas. Some nanomaterials are designed to be biocompatible and can be used in the medical field, playing an important role in disease treatment. Exosomes are nanoscale vesicles with a diameter of 30-200 nm. Studies have shown that exosomes have the effect of angiogenesis, tissue (skin, tendon, cartilage, et al.) repair and reconstruction. Nano-hydrogels are hydrogels with a diameter of 200 nm or less and can be used as the carrier to transport the exosomes into the body. Some orthopedic diseases, such as bone defects and bone infections, are difficult to handle. The emergence of nano-hydrogels coated exosomes may provide a new idea to solve these problems, improving the prognosis of patients. This review summarizes the function of nano-hydrogels coated exosomes in bone tissue repair, intending to illustrate the potential use and application of nano-hydrogels coated exosomes in bone disease.

Larger Medial Contact Area and More Anterior Contact Position in Medial-Pivot than Posterior-Stabilized Total Knee Arthroplasty during In-Vivo Lunge Activity.

This study aimed to compare the in-vivo kinematics and articular contact status between medial-pivot total knee arthroplasty (MP-TKA) and posterior stabilized (PS) TKA during weight-bearing single-leg lunge. 16 MP-TKA and 12 PS-TKA patients performed bilateral single-leg lunges under dual fluoroscopy surveillance to determine the in-vivo six degrees-of-freedom knee kinematics. The closest point between the surface models of the femoral condyle and the polyethylene insert was used to determine the contact position and area. The nonparametric statistics analysis was performed to test the symmetry of the kinematics between MP-TKA and PS-TKA. PS-TKA demonstrated a significantly greater range of AP translation than MP-TKA during high flexion (p = 0.0002). Both groups showed a significantly greater range of lateral compartment posterior translation with medial pivot rotation. The contact points of PS-TKA were located significantly more posterior than MP-TKA in both medial (10°-100°) and lateral (5°-40°, 55°-100°) compartments (p < 0.0500). MP-TKA had a significantly larger contact area in the medial compartment than in the lateral compartment. In contrast, no significant differences were observed in PS-TKA. The present study revealed no significant differences in clinical outcomes between the MP and PS groups. The PS-TKA demonstrated significantly more posterior translations than MP-TKA at high flexion. The contact points are located more posteriorly in PS-TKA compared with MP-TKA. A larger contact area and medial pivot pattern during high flexion in MP-TKA indicated that MP-TKA provides enhanced medial pivot rotation.

Greater trochanteric osteotomy and subtrochanteric osteotomy in primary/revision total hip arthroplasty.

Osteotomy of the femur is necessary in some cases of primary/revision total hip arthroplasty (THA) procedure. There are two mainly used femur osteotomy methods in THA: greater trochanteric osteotomy and subtrochanteric osteotomy. Greater trochanteric osteotomy can improve hip exposure, provide greater stability against dislocation and favorably influence the abductor moment arm. Whether in the primary or revision THA, greater trochanteric osteotomy has its unique position. Subtrochanteric osteotomy adjusts the degree of femoral de-rotation and corrects the leg length. It is widely used in hip preservation and arthroplasty surgery. All osteotomy methods have specific indications, while nonunion is the commonest complication. In this paper, we analyze the greater trochanteric osteotomy and the subtrochanteric osteotomy in primary/revision THA and summarize the characteristics of different osteotomy methods.

Medial stability and lateral flexibility of the collateral ligaments during mid-range flexion in medial-pivot total knee arthroplasty patients demonstrates favorable postoperative outcomes.

PURPOSE: The objectives of the present study were to investigate the length change in different bundles of the superficial medial collateral ligament (sMCL) and lateral collateral ligament (LCL) during lunge, and to evaluate their association with Knee Society Score (KSS) following medial-pivot total knee arthroplasty (MP-TKA). METHODS: Patients with unilateral MP-TKA knees performed a bilateral single-leg lunge under dual fluoroscopy surveillance to determine the in-vivo six degrees-of-freedom knee kinematics. The contralateral non-operated knees were used as the control group. The attachment sites of the sMCL and LCL were marked to calculate the 3D wrapping length. The sMCL and LCL were divided into anterior, intermediate, and posterior portions (aMCL, iMCL, pMCL, aLCL, iLCL, pLCL). Correlations between lengths/elongation rate of ligament bundles from full extension to 100° flexion and the KSS were examined. RESULTS: The sMCL and LCL demonstrated relative stability in length at low flexion, but sMCL length decreased whereas LCL increased with further flexion on operated knees. The sMCL length increased at low flexion and remained stable with further flexion, while the LCL length decreased with flexion on the contralateral non-operated knees. The lengths of aMCL, iMCL, and pMCL showed moderate (0.5 < r < 0.7, p < 0.05) negative correlations with the KSS, and the lengths of aLCL, iLCL, and pLCL were positively correlated with the KSS at mid flexion on operated knees (p < 0.05). The elongation rates of aLCL, iLCL, and pLCL were negatively correlated with the KSS at high flexion on operated knees (p < 0.05). However, no significant correlations between the length of different bundles of sMCL or LCL with KSS were found on contralateral non-operated knees. CONCLUSIONS: The elongation pattern of sMCL/LCL on MP-TKA knees showed differences with contralateral non-operated knees. The sMCL is tense at low to middle flexion and relaxed at high flexion, while LCL is relaxed at low to middle flexion and tense at high flexion following MP-TKA. Medial stability and proper lateral flexibility during mid flexion were associated with favorable postoperative outcomes in MP-TKA patients. In contrast, lateral relaxation at deep flexion should be avoided when applying soft-tissue balancing in MP-TKA. LEVEL OF EVIDENCE: Level III.

Alignment analysis of Brainlab knee 3 navigation-guided total knee arthroplasty using the adjusted mechanical method.

Purpose: With the application of navigation technology in Total Knee Arthroplasty (TKA), TKA procedures have become various. Studies have shown that navigation can improve the alignment of patients' lower limbs. To verify this conclusion, we collected the clinical data from patients who underwent Brainlab knee 3 navigation-guided TKA. Brainlab knee 3 is a completely new software that takes a different approach to address the current challenges of navigated TKA. During the procedure, we applied the Adjusted Mechanical Alignment (AMA) principle and took soft tissue balance as a priority. We aim to explore the patients' lower limb alignment changes who underwent the Brainlab knee 3 navigation-guided TKA using the AMA method. Methods: Fifty consecutive patients who underwent total knee arthroplasty using the Brainlab knee3 knee navigation system (Smith&Nephew) from January to August 2021 by the same doctor (Yunsu Chen) in the Department of Joint Surgery of the Shanghai Sixth People's Hospital were included. Hip-Knee-Ankle Angle (HKAA), anatomic Femur Tibia Angle (FTA), Lateral Distal Femoral Angle (LDFA), and medial proximal tibia angle (MPTA) were measured on preoperative and postoperative full-length lower-limbs x-ray films or weight-bearing anterior and lateral knee radiographs for observational and descriptive study. The preoperative and postoperative knee alignment changes were analyzed through paired t-test or nonparametric Wilcoxon test using SPSS 25.0 software. Results: Pre-operative and post-operative HKAA both obeyed normal distribution. The mean preoperative HKAA was 169.8° (154.9-178.7°) with a standard deviation of 5.41; the postoperative HKAA was 175.7° (168.4-180.0°) with a standard deviation of 2.81. Using the two-sample paired t-test to analyze, the result showed P = 0.000 < 0.05; a statistically significant difference exists. The preoperative and postoperative FTA obeyed normal distribution as well. The mean preoperative FTA was 174.7° (163.4-179.9°) with a standard deviation of 3.90; postoperative 175.6° (167.0-179.9°) with a standard deviation of 2.77. Using the two-sample paired t-test to analyze, the result showed P = 0.140 > 0.05, the difference was not statistically significant. The preoperative LDFA was normally distributed, while postoperative LDFA was not. The mean preoperative LDFA was 90.7° (83.5-99.6°) with a standard deviation of 3.83; the median of postoperative LDFA was 91.6° (86.0-103.2°) with an interquartile range of 2.93. Using the two-sample paired Wilcoxon test, the result showed P = 0.052 > 0.05; the difference was not statistically significant. Preoperative MPTA obeyed normal distribution, while postoperative MPTA did not. The mean preoperative MPTA was 83.5° (72.7-92.9°), with a standard deviation of 3.66; the median of postoperative MPTA was 89.3° (84.6-95.6°), with an interquartile range of 1.45. Using the two-sample paired Wilcoxon test, the result shows P = 0.000 < 0.05; a statistically significant difference exists. Conclusion: In our study, AMA alignment was applied in Brainlab Knee3 computer navigation-assisted total knee arthroplasty. The femoral and tibial osteotomy angles were minimally adjusted according to soft tissue situations to reduce soft tissue release. We found AMA alignment provides good control of knee alignment in the coronal plane of the lower limbs, which is a reliable technique.

Bioactive Film-Guided Soft-Hard Interface Design Technology for Multi-Tissue Integrative Regeneration.

Control over soft-to-hard tissue interfaces is attracting intensive worldwide research efforts. Herein, a bioactive film-guided soft-hard interface design (SHID) for multi-tissue integrative regeneration is shown. Briefly, a soft bioactive film with good elasticity matchable to native ligament tissue, is incorporated with bone-mimic components (calcium phosphate cement, CPC) to partially endow the soft-film with hard-tissue mimicking feature. The hybrid film is elegantly compounded with a clinical artificial ligament to act as a buffer zone to bridge the soft (ligament) and hard tissues (bone). Moreover, the bioactive film-decorated ligament can be rolled into a 3D bio-instructive implant with spatial-controllable distribution of CPC bioactive motifs. CPC then promotes the recruitment and differentiation of endogenous cells in to the implant inside part, which enables a vascularized bone growth into the implant, and forms a structure mimicking the biological ligament-bone interface, thereby significantly improving osteointegration and biomechanical property. Thus, this special design provides an effective SHID-guided implant-bioactivation strategy unreached by the traditional manufacturing methods, enlightening a promising technology to develop an ideal SHID for translational use in the future.

[Application of sliding trochanteric osteotomy in total hip arthroplasty for Crowe type â £ developmental dysplasia of the hip].

OBJECTIVE: To investigate the effectiveness of sliding trochanteric osteotomy (STO) in total hip arthroplasty (THA) for Crowe type Ⅳ developmental dysplasia of the hip (DDH). METHODS: Between July 2016 and April 2021, 52 patients (57 hips) with Crowe type Ⅳ DDH who underwent primary THA were enrolled according to inclusion criteria. There were 5 males and 47 females with a median age of 51 years (range, 18-76 years). There were 47 cases of single hip and 5 cases of bilateral hips. The leg length discrepancy (LLD) was 50.50 (44.00, 55.00) mm, visual analogue scale (VAS) score was 8.0 (6.0, 9.0), and Harris score was 58.0±5.0 before operation. Trendelenburg sign was positive in 46 patients (46 hips). All patients underwent STO and THA using Wagner-cone stem. The operation time, intraoperative blood loss, blood transfusion volume, Trendelenburg sign, and related complications were observed. During follow-up, VAS and Harris scores were recorded to evaluate the hip pain and function. X-ray film was used to measure the LLD and observe the bone union situations. RESULTS: The operation time was 90-125 minutes (mean, 105 minutes). Introperative blood loss was 420-800 mL (mean, 640 mL). Ten patients underwent blood transfusion and the amount of allogeneic blood transfusion was 2-4 U (mean, 3 U). All incisions healed by first intention after operation. All patients were followed up 4-60 months (median, 24 months). At last follow-up, LLD was 6.00 (4.00, 7.75) mm, showing significant difference when compared with that before operation ( Z=-6.278, P=0.000). After operation, 51 hips (89.5%) achieved bone union at the osteotomy site, 4 hips (7.0%) had fibrous union, and 2 hips (3.5%) had nonunion. The healing time of osteotomy was 3-12 months, with an average of 6 months. At last follow-up, the VAS score was 3.0 (2.0, 5.0) and the Harris score was 85.0±6.0. The differences between pre- and post-operation were significant ( Z=-6.176, P=0.000; t=-25.285, P=0.000). Trendelenburg sign remained positive in 4 patients (4 hips) at last follow-up and the difference was significant when compared with preoperative ( χ 2=67.947, P=0.000). One patient had a medial femoral cortical fracture when Wagner-cone stem was implanted during operation, and 2 patients had early symptoms of sciatic nerve palsy after operation, and no other related complications occurred. CONCLUSION: For Crowe type Ⅳ DDH patients, STO applied in THA can reduce the resected bone mass, provide better exposure of hip as well as improve function of hip abductor muscle. Wagner-cone stem is recommended.

Improvement of mechanical properties of zein porous scaffold by quenching/electrospun fiber reinforcement.

As a novel bone substitute material, zein-based scaffolds (ZS) should have suitable mechanical properties and porosity. ZS has shown good compressive properties matching cancellous bone, but there is still a demand to improve its mechanical properties, especially tensile and bending properties without adding plasticizers. The present study explored two simple and environment-friendly factors for this purpose: fiber reinforcement and quenching. Addition of electrospun zein fibers enhanced all mechanical properties significantly including compressive, tensile, and bending moduli; compressive and bending strengths of ZS with both higher (70-80%) and lower (50-60%) porosities, no matter whether heating treated or not treated. Especially, all these parameters were further enhanced significantly by addition of heating treated fibers. AFM provided evidence that high temperature modification could significantly alter the micro-elastic properties of zein electrospun fibers, i.e., increased stiffness of fibers. Quenching treatment also enhanced compressive, tensile, and bending strengths significantly. Finally, quenching treated ZS were implanted into critical-sized bone defects (15 mm) of the rabbit model to compare the repair efficacy with a commercial ß-tricalcium phosphate product. The results demonstrated that there were no remarkable differences in bone reconstructions between these two materials.

Loss of Knee Flexion and Femoral Rollback of the Medial-Pivot and Posterior-Stabilized Total Knee Arthroplasty During Early-Stance of Walking in Chinese Patients.

Background The medial-pivot (MP) prosthesis was developed to produce more physiological postoperative knee kinematics and better patient satisfaction than traditional prostheses, but outcomes are inconsistent in different studies of Caucasian patients. This study aimed to investigate the postoperative patient satisfaction and in vivo knee kinematics of the MP and posterior-stabilized (PS) prosthesis during gait activity in Chinese patients. Methods A retrospective analysis of 12 patients was received for this study in each MP group and PS group. Patient-reported satisfaction level and Forgotten Joint Score (FJS) were evaluated with questionnaires. A dual fluoroscopic imaging system was used to investigate in vivo knee kinematics of MP and PS total knee arthroplasty (TKA) during treadmill walking at a speed of 0.4 m/s. Results Comparable promising patient satisfaction and overall FJS (MP 60.7 ± 15.35 vs. PS 51.3 ± 17.62, p = 0.174) were found between the MP and PS groups. Peak flexion appeared at around 70% of gait cycle with values of 52.4 ± 7.4° for MP and 50.1 ± 3.6° for PS groups (no difference). Both groups maintained a stable position at the stance phase and began to translated anteriorly at toe-off with an amount of 4.5 ± 2.3 mm in the MP and 6.6 ± 2.7 mm in the PS (p = 0.08) group until late swing. The range of this external rotation motion was 5.9 ± 4.8 and 6.2 ± 4.1° (p = 0.79) for the MP and PS, respectively. Conclusion A similar knee kinematics pattern characterized by a loss of early-stance knee flexion and femoral rollback during walking was observed in the MP and PS TKAs. Our study confirmed similar effectiveness of MP TKA compared to PS TKA in Chinese patients, while the change of knee kinematics of both implants during slow walking should be noted.

Optimizing the Femoral Offset for Restoring Physiological Hip Muscle Function in Patients With Total Hip Arthroplasty.

OBJECTIVE: Femoral offset (FO) restoration is significantly correlated with functional recovery following total hip arthroplasty (THA). Accurately assessing the effects of FO changes on hip muscles following THA would help improve function and optimize functional outcomes. The present study aimed to (1) identify the impact of FO side difference on the hip muscle moment arms following unilateral THA during gait and (2) propose the optimal FO for a physiological hip muscle function. METHODS: In vivo hip kinematics from eighteen unilateral THA patients during gait were measured with a dual-fluoroscopic imaging system. The moment arms of thirteen hip muscles were calculated using CT-based 3D musculoskeletal models with the hip muscles' lines of actions. The correlation coefficient (R) between FO and hip muscle moment arm changes compared with the non-implanted hip was calculated. We considered that the FO reconstruction was satisfactory when the abductor moment arms increased, while the extensor, adductor, and flexor moment arms decreased less than 5%. RESULTS: A decreased FO following THA was significantly correlated with a decrease of the abductor and external rotator moment arms during the whole gait (R > 0.5) and a decrease of extensor moment arms during the stance phase (R > 0.4). An increased FO following THA was significantly associated with shorter flexor moment arms throughout the gait (R < -0.5) and shorter adductor moment arms in the stance phase (R < -0.4). An increase in FO of 2.3-2.9 mm resulted in increased abductor moment arms while maintaining the maximum decrease of the hip muscles at less than 5.0%. CONCLUSION: An increase of 2-3 mm in FO could improve the abductor and external rotator function following a THA. Accurate surgical planning with optimal FO reconstruction is essential to restoring normal hip muscle function in THA patients.

Correction: Chondroitin sulfate-polydopamine modified polyethylene terephthalate with extracellular matrix-mimetic immunoregulatory functions for osseointegration.

Correction for 'Chondroitin sulfate-polydopamine modified polyethylene terephthalate with extracellular matrix-mimetic immunoregulatory functions for osseointegration' by Ya-Min Li et al., J. Mater. Chem. B, 2019, 7, 7756-7770, DOI: 10.1039/C9TB01984G.

A triple-coated ligament graft to facilitate ligament-bone healing by inhibiting fibrogenesis and promoting osteogenesis.

Absence of ligament-bone healing due to poor bioactivity and hyperplasia of fibrous tissue caused by immune response severely impairs ligament grafts' functional duration in anterior cruciate ligament (ACL) reconstruction. While osteogenic modification is a popular technique for promoting ligament-bone integration, inadequate osseointegration remains a common experience, due to occupying fibrous hyperplasia and impaired osteogenesis potential. In the present study, a triple-nano-coating polyethylene terephthalate (PET) graft was developed by polydopamine self-assembly, chondroitin sulfate (CS) chemical-grafting and BMP-2 physical-immobilization to facilitate robust ligament-bone healing, The CS/polydopamine-modified PET (C-pPET) graft was demonstrated to inhibit fibrogenesis by regulating polarization of macrophages and promoting the secretion of anti-inflammatory factors. Moreover, the immunoregulatory function of CS cooperated with BMP-2 to facilitate osteogenic differentiation of stem cells, promoting the expression of ALP, Runx2, OCN and COL I. Bone regeneration was significantly enhanced at early-middle stage in the BMP-loaded pPET (B/pPET) group, while occurring at middle-late stage in the C-pPET group. Continuous new bone formation and optimal ligament-bone healing were observed in the B/C-pPET group via sequential and synergistic immune osteogenesis by CS and cytokine osteogenesis by BMP-2. Thus, the present study revealed a practical avenue for the promotion of ligament-bone healing through the development of a triple-nano-coating engineered ligament combining immunoregulatory anti-fibrogenesis and sequential-synergistic osteogenesis, which holds a great potential for improving the clinical efficacy of ligament graft in ACL reconstruction. STATEMENT OF SIGNIFICANCE: A triple-nano-coating polyethylene terephthalate (PET) graft was developed by polydopamine self-assembly, chondroitin sulfate (CS) chemical-grafting and BMP-2 physical-immobilization to facilitate robust ligament-bone healing. This study demonstrated that the multifunctional ligament grafts could reshape the local immune microenvironment by regulating macrophage phenotype and immune cytokine secretion to inhibit the fibrous hyperplasia and regulate stem cell towards osteogenic differentiation to promote bone regeneration. The present study demonstrates that efficient ligament-bone healing is achieved via the combination of immunoregulatory anti-fibrogenesis and dual osteogenesis of immunoregulation and cytokine induction.

Adverse effects of total hip arthroplasty on the hip abductor and adductor muscle lengths and moment arms during gait.

BACKGROUND: Precise evaluation of the hip abductor and adductor muscles function in total hip arthroplasty (THA) patients during gait could help prevent postoperative complications and optimize the rehabilitation training program. The purpose of this study was to elucidate the effects of THA on the hip abductor and adductor muscle lengths and moment arms of in vivo patients during gait. METHODS: Ten unilateral THA patients received CT scans and dual fluoroscopic imaging for the hip kinematics during gait. The hip abductor and adductor muscle insertions were digitized on the 3D hip model for the determination of their dynamic lines of action and moment arms. Changes in the hip abductor and adductor muscle lengths and moment arms of THA patients between the implanted and non-implanted sides were quantified during gait. RESULTS: The adductor longus, adductor brevis, and pectineus of the implanted hips had significantly (P < 0.05) less elongation than that of the non-implanted side during the stance phase. The gluteus medius, gluteus minimus, and piriformis moment arms of the implanted side were significantly shorter. The piriformis muscle moment arm was significantly larger. In the double support phase, the adductor magnus and adductor longus moment arms of the implanted sides were significantly decreased. CONCLUSIONS: Results suggested that the adverse effects of THA on hip stability. Development of a rehabilitation program considering the effects of THA is essential. Accurate surgical techniques may reduce the impact of THA on the peripheral muscles.

Chondroitin sulfate-polydopamine modified polyethylene terephthalate with extracellular matrix-mimetic immunoregulatory functions for osseointegration.

Optimal integration between the polyethylene terephthalate (PET) graft and host bone is a prerequisite to obtain a satisfactory outcome after graft implantation for ligament reconstruction. Recent studies indicate that complex biosignals including immunoregulation, cell recruitment, and osteogenic differentiation provided by the extracellular matrix (ECM) are conducive to promoting osseointegration. In the present study, a chondroitin sulfate (CS)/polydopamine-modified PET graft was developed to regulate the local immune microenvironment, guide stem cell behavior, and promote new bone formation. We found that CS-modified PET grafts significantly regulated the macrophage phenotype switching from M1 to M2 and promoted the expression of pro-repair cytokines including interleukin (IL)-4, IL-10 and transforming growth factor (TGF)-ß1. Moreover, the immunoregulatory function of CS-modified PET guided stem cell behaviors, including recruitment, adhesion, and proliferation, and enhanced the osteogenic differentiation of stem cells. In vivo experiments confirmed that CS-modified PET switched the local immune microenvironment status from pro-inflammatory to anti-inflammatory, up-regulated osteogenic marker expression, and promoted the bone regeneration process, so as to achieve graft-bone osseointegration. These results indicate that an ECM-biomimetic immunoregulatory coating is an effective approach to promote graft integration. This study proposes an effective strategy for an artificial graft to achieve graft-bone osseointegration through immunoregulatory osteogenesis.

Formulation of zein based compression coated floating tablets for enhanced gastric retention and tunable drug release.

The present study aimed to investigate the potential of zein (a protein obtained from corn) for development of gastroretentive floating tablets for the first time. A compression coated tablet design with outer floating layer and inner drug containing layer was followed to achieve floating over gastric fluid with sustained release of drug. Captopril was used as a model drug for this purpose. Eight formulations were developed and the influence of different components on drug release and floating behavior was evaluated. The drug in coating layer was found to be released at faster rate while sustained release behavior was observed from core layer. In vivo pharmacokinetic studies on rabbits showed significant increase in bioavailability and mean residence time (MRT). Moreover, radiographic study exhibited gastric retention of prepared tablets >12 h. In conclusion, zein can be used for development of gastroretentive floating tablets and by adjusting amount of different formulation factors, desired drug release rate can be achieved.

[Comparison of combined intravenous and topical use of tranexamic acid with different dosage in primary total knee arthroplasty].

Objective: To compare the efficacy and safety of intra-articular combined with intravenous administration of tranexamic acid (TXA) with different dosage for reducing blood loss in primary total knee arthroplasty (TKA). Methods: Between January 2017 and June 2017, 90 patients suffering from unilateral osteoarthritis who underwent primary TKA were randomly scheduled to three interventions, named groups A, B, and C. Single dosage of TXA via intravenous injection (IV) and different dosages of TXA via intra-articular injection (IA) were utilized in three groups, respectively. All patients in three groups received 1 g TXA IV at 10 minutes preoperatively, and received 1, 2, and 3 g TXA IA diluted in 50 mL saline after wound closure in groups A, B and C, respectively. The age, gender, body mass index, affected side of the knee, grade of osteoarthritis, grade of America Society of Anesthesiologist, preoperative hemoglobin (Hb) concentration, platelet count, preoperative prothrombin time, and activated partial thromboplastin time were not significantly different between groups ( P>0.05). The postoperative wound blood drainage, Hb concentration at 1, 3, and 7 days after operation, transfusion rate, and thromboembolic complications were observed. All patients were routinely observed for deep vein thrombosis (DVT) by the color Doppler ultrasonography at 1 week, 1 month, and 3 months after operation, and the symptomatic pulmonary embolism (PE) were observed. Results: All patients in three groups were followed up 7-12 months (mean, 8.4 months). There was no significant difference in operation time between groups ( P>0.05). The postoperative wound blood drainage was significantly less in groups B and C than that in group A ( P<0.05), whereas no significant difference was found between group B and group C ( P>0.05). Incision skin necrosis occurred in 1 case of group B and fat liquefaction occurred in 1 case of group C. The other incisions of 3 groups healed by first intention. There was no significant difference in incision complication incidence between groups. The Hb concentration was significantly higher in groups B and C than that in group A at 1, 3, and 7 days after operation ( P<0.05). While between group B and group C, the significant difference of Hb concentration only existed at 1 day after operation ( P<0.05). The number of patients who got blood transfusion was significantly less in group B (4 cases, 13.3%) and group C (5 cases, 16.7%) than that in group A (9 cases, 30%) ( P< 0.05), but no significant difference was found between group B and group C ( P>0.05). The result of color Doppler ultrasonography showed that 1 case got DVT in the contralateral calf at 3 weeks in group B. And there was no symptomatic PE in 3 groups. Conclusion: Combined administration of IV and IA TXA in a clinically relevant reduction in blood loss was effective and safe in primary TKA, and no thromboembolic complication was observed. The combination of 1 g IV with 2 g IA could be the optional choice.

Emodin attenuates titanium particle-induced osteolysis and RANKL-mediated osteoclastogenesis through the suppression of IKK phosphorylation.

Aseptic loosening due to wear particles is a serious challenge for orthopedic surgeons, sabotaging the long-term success of total joint arthroplasty. The existing treatments for aseptic loosening are still far from satisfactory, necessitating more aggressive drug exploration. Here, we examined the effect of emodin on titanium particle-induced osteolysis and further investigated its underlying mechanism in vivo and in vitro. Thirty-two C57BL/6 mice were randomly assigned into four groups: the Sham group (sham operation with vehicle injection), Vehicle group (titanium particle treatment with vehicle injections), Low group (titanium particle treatment with injections of 10 mg/kg/day emodin) and High group (titanium particle treatment with injections of 50 mg/kg/day emodin). Micro-CT scanning and histological analysis revealed that after emodin injections, the inflammatory response and bone destruction were markedly ameliorated. TRAP staining showed that osteoclast numbers were also dramatically reduced. Throughout the in vitro culture period, emodin significantly decreased the bone resorption area, number of osteoclasts and formation of F-actin rings. Mechanistic studies suggested that reduced NF-κB signaling might be mediating the inhibitory effects of emodin. Collectively, our findings suggest that emodin, a natural product extracted from Rheum palmatum, may be developed as a promising candidate for the treatment of wear particle-induced osteolysis and subsequent aseptic loosening.

In vivo analysis of the effects of CoCrMo and Ti particles on inflammatory responses and osteolysis.

Metal wear particles play a major role in periprosthetic osteolysis and aseptic loosening in patients with total joint arthroplasty. The ability to induce osteolysis depends on the size, shape, dose, and type of the particles. However, much remains unknown regarding which type of metal particles are most reactive. We compared the inflammatory response and bone loss induced by two metal wear particles, cobalt-chromium-molybdenum (CoCrMo) and titanium (Ti), in a mouse calvaria model of osteolysis. We found that CoCrMo particles caused markedly greater bone resorption than Ti particles, according to three-dimensional images of the calvariae. CoCrMo particles activated more functional osteoclasts by significantly increasing the expression of the osteoclast-specific gene tartrate-specific acid phosphatase (Trap), calcitonin receptor (Ctr), and nuclear factor of activated T cells c1 (Nfatc1), and induced a greater increase in the ratio of receptor activator of nuclear factor kappa B ligand (RANKL)/osteoprotegerin (OPG) than Ti particles. CoCrMo particles also induced a stronger local inflammatory response, markedly increasing the expression and secretion of tumor necrosis factor-α and interleukin-1ß compared with Ti particles. Therefore, CoCrMo particles induced a more severe inflammatory response and greater osteolysis than Ti particles in vivo.

Anthocyanin suppresses CoCrMo particle-induced osteolysis by inhibiting IKKα/ß mediated NF-κB signaling in a mouse calvarial model.

Wear particle-induced osteolysis and bone resorption have been identified as critical factors of implant failure and total joint revision, in which nuclear factor kappa B (NF-κB) signaling and chronic inflammation have been shown to play key roles. Although anthocyanin is known to have anti-inflammatory function via blocking NF-κB pathway, it is still unclear whether anthocyanin has a protective effect on particle-induced osteolysis. In the present study, we aimed to investigate the detailed effects and the underlying mechanism of anthocyanin on CoCrMo particle-induced osteolysis in a mouse calvavial model. One hundred and twelve male BALB/c mice were divided randomly into four groups: sham group (sham operation and injection with PBS), vehicle group (CoCrMo particle treatment and injection with PBS), low-dose anthocyanin group (CoCrMo particle treatment and injecting anthocyanin with 0.1mg/g/day), and high-dose anthocyanin group (CoCrMo particle treatment and injecting anthocyanin with 0.4mg/g/day). Mice were sacrificed after two weeks, harvesting the calvariae tissue for in depth analysis by micro-CT, histomorphometry, immunohistochemical and molecular biology analysis. As expected, anthocyanin markedly inhibited CoCrMo particle-induced inflammatory infiltration and decreased bone loss in vivo. Anthocyanin also reversed the increase in the ratio of receptor activator of nuclear factor kappa B ligand (RANKL)/osteoproteger (OPG) and suppressed osteoclast formation in CoCrMo particle-stimulated calvaria. Additionally, anthocyanin significantly reduced the expression and secretion of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) in the calvaria of CoCrMo-stimulated mice. Furthermore, we confirmed that anthocyanin attenuated osteolysis by blocking NF-κB pathway via inhibiting inhibitor of nuclear factor kappa-B kinase α/ß (IKKα/ß) phosphorylation. In conclusion, our study demonstrated that anthocyanin can protect against CoCrMo particle-induced inflammatory osteolysis via inhibiting the IKKα/ß-NF-κB pathway, and have a potential therapeutic effect on the treatment of wear particle-induced osteolysis.