Development and evaluation of an injectable ChitHCl-MgSO4-DDA hydrogel for bone regeneration: In vitro and in vivo studies on cell migration and osteogenesis enhancement.

Nonunion and delayed union of the bone are situations in orthopedic surgery that can occur even if the bone alignment is correct and there is sufficient mechanical stability. Surgeons usually apply artificial bone grafts in bone fracture gaps or in bone defect sites for osteogenesis to improve bone healing; however, these bone graft materials have no osteoinductive or osteogenic properties, and fit the morphology of the fracture gap with difficulty. In this study, we developed an injectable chitosan-based hydrogel with MgSO4 and dextran oxidative, with the purpose to improve bone healing through introducing an engineered chitosan-based hydrogel. The developed hydrogel can gelate and fit with any morphology or shape, has good biocompatibility, can enhance the cell-migration capacity, and can improve extracellular calcium deposition. Moreover, the amount of new bone formed by injecting the hydrogel in the bone tunnel was assessed by an in vivo test. We believe this injectable chitosan-based hydrogel has great potential for application in the orthopedic field to improve fracture gap healing.

Biofunctionalized hydrogel composed of genipin-crosslinked gelatin/hyaluronic acid incorporated with lyophilized platelet-rich fibrin for segmental bone defect repair.

Segmental bone defects can arise from trauma, infection, metabolic bone disorders, or tumor removal. Hydrogels have gained attention in the field of bone regeneration due to their unique hydrophilic properties and the ability to customize their physical and chemical characteristics to serve as scaffolds and carriers for growth factors. However, the limited mechanical strength of hydrogels and the rapid release of active substances have hindered their clinical utility and therapeutic effectiveness. With ongoing advancements in material science, the development of injectable and biofunctionalized hydrogels holds great promise for addressing the challenges associated with segmental bone defects. In this study, we incorporated lyophilized platelet-rich fibrin (LPRF), which contains a multitude of growth factors, into a genipin-crosslinked gelatin/hyaluronic acid (GLT/HA-0.5 % GP) hydrogel to create an injectable and biofunctionalized composite material. Our findings demonstrate that this biofunctionalized hydrogel possesses optimal attributes for bone tissue engineering. Furthermore, results obtained from rabbit model with segmental tibial bone defects, indicate that the treatment with this biofunctionalized hydrogel resulted in increased new bone formation, as confirmed by imaging and histological analysis. From a translational perspective, this biofunctionalized hydrogel provides innovative and bioinspired capabilities that have the potential to enhance bone repair and regeneration in future clinical applications.

Fortification of Iron Oxide as Sustainable Nanoparticles: An Amalgamation with Magnetic/Photo Responsive Cancer Therapies.

Due to their non-toxic function in biological systems, Iron oxide NPs (IO-NPs) are very attractive in biomedical applications. The magnetic properties of IO-NPs enable a variety of biomedical applications. We evaluated the usage of IO-NPs for anticancer effects. This paper lists the applications of IO-NPs in general and the clinical targeting of IO-NPs. The application of IONPs along with photothermal therapy (PTT), photodynamic therapy (PDT), and magnetic hyperthermia therapy (MHT) is highlighted in this review's explanation for cancer treatment strategies. The review's study shows that IO-NPs play a beneficial role in biological activity because of their biocompatibility, biodegradability, simplicity of production, and hybrid NPs forms with IO-NPs. In this review, we have briefly discussed cancer therapy and hyperthermia and NPs used in PTT, PDT, and MHT. IO-NPs have a particular effect on cancer therapy when combined with PTT, PDT, and MHT were the key topics of the review and were covered in depth. The IO-NPs formulations may be uniquely specialized in cancer treatments with PTT, PDT, and MHT, according to this review investigation.

The Complex Interplay between Imbalanced Mitochondrial Dynamics and Metabolic Disorders in Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) is a global burden, with an increasing number of people affected and increasing treatment costs. The advances in research and guidelines improve the management of blood glucose and related diseases, but T2DM and its complications are still a big challenge in clinical practice. T2DM is a metabolic disorder in which insulin signaling is impaired from reaching its effectors. Mitochondria are the "powerhouses" that not only generate the energy as adenosine triphosphate (ATP) using pyruvate supplied from glucose, free fatty acid (FFA), and amino acids (AA) but also regulate multiple cellular processes such as calcium homeostasis, redox balance, and apoptosis. Mitochondrial dysfunction leads to various diseases, including cardiovascular diseases, metabolic disorders, and cancer. The mitochondria are highly dynamic in adjusting their functions according to cellular conditions. The shape, morphology, distribution, and number of mitochondria reflect their function through various processes, collectively known as mitochondrial dynamics, including mitochondrial fusion, fission, biogenesis, transport, and mitophagy. These processes determine the overall mitochondrial health and vitality. More evidence supports the idea that dysregulated mitochondrial dynamics play essential roles in the pathophysiology of insulin resistance, obesity, and T2DM, as well as imbalanced mitochondrial dynamics found in T2DM. This review updates and discusses mitochondrial dynamics and the complex interactions between it and metabolic disorders.

Comparison of two different types of hybrid Tibial fixations for anterior cruciate ligament reconstruction: a prospective comparative cohort study.

BACKGROUND: Previous studies have compared different kinds of fixations for anterior cruciate ligament reconstruction. Nevertheless, there is no optimal method to date. To the best of authors' knowledge, there is no article discussing the combination of adjustable suspensory device and interference screw for hybrid tibial fixation. METHODS: In total, 66 patients (n = 34, adjustable suspensory device and interference screw; n = 32, cortical screw and interference screw) were analyzed. Their International Knee Documentation Committee score and Tegner activity level scale were evaluated before and after a 2-year follow-up. The Single Assessment Numeric Evaluation score was evaluated after a 2-year follow-up. Physical exams such as range of motion, anterior knee pain (VAS > = 3) and Lachman test were assessed before and at least 12 months after surgery. To evaluate tunnel widening, anteroposterior and lateral view radiography was conducted 1 day and at least 12 months after surgery. A more than 10% change was considered tibial tunnel widening. Mann-Whitney U test, independent t test, paired t test, Fisher's exact test and chi-squared test were used to compare the variables. Linear and logistic regression models were applied to adjust for potential confounders. RESULTS: No variable except gender (P = 0.006) showed significant difference with regard to demographic data. After adjustment, there was no statistically significant difference between the groups regarding post-operative physical exams. Patients who used adjustable suspensory device and interference screw had lower post-operative Single Assessment Numeric Evaluation score (adjusted ß - 8.194; P = 0.017), Tegner activity level scale (adjusted ß - 1.295; P = 0.001) and pre-operative degrees of knee flexion (adjusted ß - 2.825; P = 0.026). Less percentage of tunnel widening in the lateral view of radiographs was seen in patients in group of adjustable suspensory device and interference screw (adjusted ß - 1.733; P = 0.038). No significant difference was observed in the anteroposterior view of radiographs (adjusted ß - 0.667; P = 0.26). CONCLUSION: In these 66 patients, we observed less tibial tunnel widening and lower post-operative functional scores in the group of adjustable suspensory device and interference screw. Both groups displayed similar outcomes of physical exams as well as improvement after operation. The proposed method may become an alternative option. Nonetheless, the quality of our study is still limited, and thus further studies are warranted to determine the efficacy and further application. TRIAL REGISTRATION: Joint Institutional Review Board of Taipei Medical University, Taipei, Taiwan (No: N201805094 ). STUDY DESIGN: Prospective comparative cohort study; Level of evidence, II.

Combining Mg-Zn-Ca Bulk Metallic Glass with a Mesoporous Silica Nanocomposite for Bone Tissue Engineering.

Mg-Zn-Ca bulk metallic glass (BMG) is a promising orthopedic fixation implant because of its biodegradable and biocompatible properties. Structural supporting bone implants with osteoinduction properties for effective bone regeneration have been highly desired in recent years. Osteogenic growth peptide (OGP) can increase the proliferation and differentiation of mesenchymal stem cells and enhance the mineralization of osteoblast cells. However, the short half-life and non-specificity to target areas limit applications of OGP. Mesoporous silica nanoparticles (MSNs) as nanocarriers possess excellent properties, such as easy surface modification, superior targeting efficiency, and high loading capacity of drugs or proteins. Accordingly, we propose a system of combining the OGP-containing MSNs with Mg-Zn-Ca BMG materials to promote bone regeneration. In this work, we conjugated cysteine-containing OGP (cgOGP, 16 a.a.) to interior walls of channels in MSNs and maintained the dispersity of MSNs via PEGylation. An in vitro study showed that metal ions released from Mg-Zn-Ca BMG promoted cell proliferation and migration and elevated alkaline phosphatase (ALP) activity and mineralization. On treating cells with both BMG ion-containing Minimum Essential Medium Eagle-alpha modification (α-MEM) and OGP-conjugated MSNs, enhanced focal adhesion turnover and promoted differentiation were observed. Hematological analyses showed the biocompatible nature of this BMG/nanocomposite system. In addition, in vivo micro-computed tomographic and histological observations revealed that our system stimulated osteogenesis and new bone formation around the implant site.

Comparison of minimally invasive percutaneous fixation and open reduction internal fixation for patella fractures: a meta-analysis.

BACKGROUND: Open reduction internal fixation (ORIF) has long been the conventional procedure for managing displaced patella fracture. This surgical approach has certain drawbacks, which might affect clinical outcomes and patient prognosis. Minimally invasive percutaneous fixation (MIPF) was proposed to overcome these disadvantages. Few in-depth investigations have been performed to determine the superiority of MIPF over ORIF. The aim of this study was to compare the efficacies of MIPF and ORIF for patella fractures. METHODS: The PubMed, Cochrane Library, Embase, and Scopus databases were searched for relevant studies from November 26 to December 17, 2020. Non-English publications and pediatric orthopedic articles were excluded. Statistical analysis was performed using Review Manager, version 5.4, with mean differences (MDs), standardized mean differences (SMDs), odds ratios (ORs), and respective 95% confidence intervals (CIs) calculated using a random effects model. The primary outcomes were the pain score, knee range of motion, and joint functionality. The secondary outcomes were the surgical time, complications, and implant removal rate. RESULTS: Six articles with a total of 304 patients were included in the meta-analysis. Pooled analysis revealed that patients with MIPF had a significantly reduced pain score (MD = - 1.30, 95% CI = - 1.77 to -0.82; p < 0.00001) and increased knee extension angles (MD = 0.72, 95% CI = 0.18 to 1.25; p = 0.009) at 3-month follow-up. Furthermore, knee flexion angles (MD = 8.96, 95% CI = 5.81 to 12.1; p < 0.00001) and joint functionality (SMD = 0.54, 95% CI = 0.21 to 0.86; p = 0.001) had statistically improved at 2 years. However, no difference was observed between MIPF and ORIF with regard to the surgical time. The risk of complications (OR = 0.10, 95% CI = 0.05 to 0.18; p < 0.00001) and implant removal rate (OR = 0.20, 95% CI = 0.07 to 0.57; p = 0.003) were significantly lower with MIPF than with ORIF. CONCLUSIONS: MIPF is more favorable than ORIF in terms of the pain score, knee range of motion, joint functionality, complications, and implant removal rate. Thus, it can be adopted as an alternative to ORIF.

Bioactive Glass Fiber-Reinforced Plastic Composites Prompt a Crystallographic Lophelia Atoll-Like Skeletal Microarchitecture Actuating Periosteal Cambium.

The touchstone for bone replacing or anchoring trauma implants, besides resorption, includes functional ankylosis at a fixation point and replacement by viable functional neo-bone tissues. These parameters redefined the concept of "resorbability" as "bioresorbability." Interference screws are the most commonly used resorbable anchoring implants for anterior cruciate ligament (ACL) reconstruction (surgery). Over the years, the bioresorbable screw fixation armamentarium has amplified countless choices, but instability and postimplantation complications have raised concerns about its reliability and efficacy. Owing to this interest, in this work, bioactive glass fiber-reinforced plastic (BGFP) composites with (BGFPnb5) and without (BGFP5) niobicoxide composing multiplexed network modifiers are reported as bioresorbable bone-anchoring substitutes. These synergistically designed composites have a fabricated structure of continuous, unidirectional BG fibers reinforced in an epoxy resin matrix using "melt-drawing and microfabrication" technology. The BGFP microarchitecture is comprised of multiplexed oxide components that influence bioactive response in a distinctive lophelia atoll-like apatite formation. Furthermore, it assists in the proliferation, adherence, and migration of bone marrow-derived mesenchymal stem cells. It also exhibits superior physicochemical characteristics such as surface roughness, hydrophilic exposure, distinctive flexural strength, and bioresorption. Thus, it induces restorative bone osseointegration and osteoconduction and actuates periosteum function. In addition, the BGFP influences the reduction of DH5-α Escherichia coli in suspension culture, demonstrating potential antibacterial efficacy. In conclusion, the BGFP composite therapeutic efficacy demonstrates distinctive material characteristics aiding in bone regeneration and restoration that could serve as a pioneer in orthopedic regenerative medicine.

Photothermal-Irradiated Polyethyleneimine-Polypyrrole Nanopigment Film-Coated Polyethylene Fabrics for Infrared-Inspired with Pathogenic Evaluation.

Influenza, pneumonia, and pathogenic infection of the respiratory system are boosted in cold environments. Low temperatures also result in vasoconstriction, restraint of blood flow, and decreased oxygen to the heart, and the risk of a heart attack would increase accordingly. The present face mask fabric fails to preserve its air-filtering function as its electrostatic function vanishes once exposed to water. Therefore, its filtering efficacy would be decreased meaningfully, making it nearly impracticable to reuse the disposable face masks. The urgent requirement for photothermal fabrics is also rising. Nanobased polyethyleneimine-polypyrrole nanopigments (NPP NPs) have been developed and have strong near-infrared spectrum absorption and exceptional photothermal convertible performance. Herein, the mask fabric used PE-fiber-constructed membrane (PEFM) was coated by the binding affinity of the cationic polyethyleneimine component of NPP NPs forming NPP NPs-PEFM. To the best of our knowledge, no study has investigated NPP NP-coated mask fabric to perform infrared red (solar or body) photothermal conversion efficacy to provide biocompatible warming, remotely photothermally captured antipathogen, and antivasoconstriction in vivo. This pioneering study showed that the developed NPP NPs-PEFM could be washable, reusable, breathable, biocompatible, and photothermal conversable for active eradication of pathogenic bacteria. Further, it possesses warming preservation and antivasoconstriction.

Injury mechanism affects the stability of suture-button syndesmosis fixation.

BACKGROUND: Ankle syndesmosis injury is a common condition, and the injury mechanism can be sorted into pure syndesmosis injury, Weber-B, and Weber-C type fractures. This study aims to evaluate the treatment outcomes and stability of suture-button fixation for syndesmosis injury with different injury mechanisms. We hypothesized that injury mechanisms would alter the stability of suture-button fixation. METHODS: We retrospectively reviewed 63 patients with ankle syndesmosis injury who underwent surgery with TightRope (Arthrex, Naples, FL, USA) from April 2014 to February 2019. The stability of suture-button fixation with TightRope was evaluated by comparing the preoperative, postoperative, and final follow-up measurements of tibiofibular clear space (TFCS), tibiofibular overlap (TFO), and medial clear space (MCS). A subgroup analysis for each demographic group and injury type including pure syndesmosis injury, Weber-B, and Weber-C type fractures were performed. RESULTS: Syndesmosis was effectively reduced using TightRope. After the index surgery, the tibiofibular clear space was reduced from 7.73 to 4.04 mm, the tibiofibular overlap was increased from 3.05 to 6.44 mm, and the medial clear space was reduced from 8.12 to 3.54 mm. However, syndesmosis widening was noted at the final follow-up, especially in Weber-C type fractures (TFCS 3.82 to 4.45 mm, p < 0.01 and TFO 6.86 to 6.29 mm, p = 0.04). Though widened, the final follow-up values of tibiofibular clear space and tibiofibular overlap were in the acceptable range. Postoperatively and at the final follow-up, medial clear space was found to be significantly larger in the Weber-C group than in the pure syndesmosis and Weber-B groups (p < 0.05). CONCLUSIONS: Suture-button fixation can offer anatomic reduction and dynamic fixation in syndesmosis injuries. However, when using this modality for Weber-C type fractures, more attention should be focused on the accuracy of reduction, especially of medial clear space, and rediastasis should be carefully monitored. TRIAL REGISTRATION: This trial was retrospectively approved by TMU-JIRB. Registration number N202004122, and the date of approval was May 06, 2020. LEVEL OF EVIDENCE: III.

Novel transplant of combined platelet-rich fibrin Releasate and bone marrow stem cells prevent bone loss in Ovariectomized osteoporotic mice.

BACKGROUND: Osteoporosis is a metabolic bone disorder characterized by deterioration in the quantity and quality of bone tissue, with a consequent increase susceptibility to fracture. METHODS: In this study, we sought to determine the efficacy of platelet-rich fibrin releasates (PRFr) in augmenting the therapeutic effects of stem cell-based therapy in treating osteoporotic bone disorder. An osteoporosis mouse model was established through bilateral ovariectomy on 12-week-old female ICR (Institute of Cancer Research) mice. Eight weeks postoperatively, the ovariectomized (OVX) mice were left untreated (control) or injected with PRFr, bone marrow stem cells (BMSCs), or the combination of BMSCs and PRFr. Two different injection (single versus quadruple) dosages were tested to investigate the accumulative effects of BMSCS and PRFr on bone quality. Eight weeks after injection, the changes in tibial microstructural profiles included the percentage of bone volume versus total tissue volume (BV/TV, %), bone mineral density (BMD, g/cm3), trabecular number (Tb.N, number/mm), and trabecular separation (Tb.Sp, mm) and bony histology were analyzed. RESULTS: Postmenopausal osteoporosis model was successfully established in OVX mice, evidenced by reduced BMD, decreased BV/TV, lower Tb.N but increased Tb.Sp. Eight weeks after injection, there was no significant change to BMD and bone trabeculae could be detected in mice that received single-injection regimen. In contrast, in mice which received 4 doses of combined PRFr and BMSCs, the BMD, BV/TV, and TB.N increased, and the TB.Sp decreased significantly compared to untreated OVX mice. Moreover, the histological analysis showed the trabecular spacing become narrower in OVX-mice treated with quadruple injection of BMSCs and combined PRFr and BMSCs than untreated control. CONCLUSION: The systemic administration of combined BMSCs and PRFr protected against OVX-induced bone mass loss in mice. Moreover, the improvement of bony profile scores in quadruple-injection group is better than the single-injection group, probably through the increase in effect size of cells and growth factors. Our data also revealed the combination therapy of BMSCs and PRFr has better effect in enhancing osteogenesis, which may provide insight for the development of a novel therapeutic strategy in osteoporosis treatment.

Concentrated stress effects of contoured and non-contoured high Tibial osteotomy plates: A finite-element study.

BACKGROUND: The TomoFix plate has been extensively used in high tibial osteotomy surgery to stabilize the distracted tibial bones. However, distal pain related to plate irritation was considered one of the most relevant complications for this fixation device. This study aimed to correlate reports of distal pain with the profiles of the distracted tibia and initial plate and plate contour. METHODS: This study used the finite-element method to investigate the profile-, distraction-, and contour-induced effects on stress distribution of the distal tibia-plate contact. The associations of two tibia profiles (normal and concave), distraction angles, and two plate profiles (contoured and non-contoured) were discussed in this study. The areas and stresses of the distal tibia-plate contact were chosen as comparison indices. FINDINGS: Before weight-bearing, the non-contoured plates of the normal and concave tibia profiles consistently showed less contact area at the distal tibia-plate region. Consequently, the physiological loads make the non-contoured plate subject to more concentrated bone stresses and thus may induce more pain at the distal tibia-plate region than a contoured plate. When the distraction angle decreases, the tibia-plate gap increases. Prior to fixation, the tibia-plate gap can be evaluated by the profiles of the distracted tibia and non-contoured plate by use of anteroposterior radiograph and computer-aided simulation. INTERPRETATION: In the situations of a lower distraction angle or a large tibia-plate gap, the use of a plate bender or a lag screw is recommended in order to contour the plate for reducing the concentrated stress at the distal tibia-plate region.

Thermosensitive Chitosan-Gelatin-Glycerol Phosphate Hydrogels as Collagenase Carrier for Tendon-Bone Healing in a Rabbit Model.

Healing of an anterior cruciate ligament graft in bone tunnel yields weaker fibrous scar tissue, which may prolong an already prolonged healing process within the tendon-bone interface. In this study, gelatin molecules were added to thermosensitive chitosan/ß-glycerol phosphate disodium salt hydrogels to form chitosan/gelatin/ß-glycerol phosphate (C/G/GP) hydrogels, which were applied to 0.1 mg/mL collagenase carrier in the tendon-bone junction. New Zealand white rabbit's long digital extensor tendon was detached and translated into a 2.5-mm diameter tibial plateau tunnel. Thirty-six rabbits underwent bilateral surgery and hydrogel injection treatment with and without collagenase. Histological analyses revealed early healing and more bone formation at the tendon-bone interface after collagenase partial digestion. The area of metachromasia significantly increased in both 4-week and 8-week groups after collagenase treatment (p < 0.01). Micro computed tomography showed a significant increase in total bone volume and bone volume/tissue volume in the 8 weeks after collagenase treatment, compared with the control group. Load-to-failure was significantly higher in the treated group at 8 weeks (23.8 ± 8.13 N vs 14.3 ± 3.9 N; p = 0.008). Treatment with collagenase digestion resulted in a 66% increase in pull-out strength. In conclusion, injection of C/G/GP hydrogel with collagenase improves tendon-to-bone healing in a rabbit model.

Microplasma Cross-Linked Graphene Oxide-Gelatin Hydrogel for Cartilage Reconstructive Surgery.

Herein, we report the cartilage tissue engineering application of nanographene oxide (NGO)-reinforced gelatin hydrogel fabricated by utilizing a microplasma-assisted cross-linking method. NGO sheets with surface functionalities were introduced to enhance the mechanical and biomedical properties of gelatin-based hydrogels. Highly energetic reactive radicals were generated from the nonthermal plasma (NTP), which is used to facilitate the cross-linking and polymerization during the polymeric hydrogel fabrication. The NTP treatment substantially reinforced a small amount (1 wt %) of NGO into the gelatin hydrogel. Systematic material characterization thus shows that the fabricated hydrogel possessed unique properties such as moderate surface roughness and adhesiveness, suitable pores sizes, temperature-dependent viscoelasticity, and controllable degradability. In vitro studies demonstrated that the as-fabricated hydrogel exhibited excellent cell-material interactions with SW 1353 cells, bone marrow-derived mesenchymal stem cells, and a rat chondrocyte cell line, thereby exhibiting appropriate cytocompatibility for cartilage tissue engineering applications. Furthermore, an in vivo study indicated that the formation of a healthy hyaline cartilage after the microfracture was enhanced by the fabricated hydrogel implant, offering a potential biocompatible platform for microfracture-based cartilage reconstructive surgery.

Effects of Genital Nerve Stimulation Amplitude on Bladder Capacity in Spinal Cord Injured Subjects.

BACKGROUND/PURPOSE: Few studies have investigated the effects of changing the amplitude of dorsal genital nerve stimulation (GNS) on the inhibition of neurogenic detrusor overactivity in individuals with spinal cord injury (SCI). The present study determined the acute effects of changes in GNS amplitude on bladder capacity gain in individuals with SCI and neurogenic detrusor overactivity. METHODS: Cystometry was used to assess the effects of continuous GNS on bladder capacity during bladder filling. The cystometric trials were conducted in a randomized sequence of cystometric fills with continuous GNS at stimulation amplitudes ranging from 1 to 4 times of threshold (T) required to elicit the genitoanal reflex. RESULTS: The bladder capacity increased minimally and maximally by approximately 34% and 77%, respectively, of the baseline bladder capacity at 1.5 T and 3.2 T, respectively. Stimulation amplitude and bladder capacity were significantly correlated (R = 0.55, P = 0.01). CONCLUSION: This study demonstrates a linear correlation between the stimulation amplitude ranging from 1 to 4T and bladder capacity gain in individuals with SCI in acute GNS experiments. However, GNS amplitude out of the range of 1-4T might not be exactly a linear relationship due to subthreshold or saturation factors. Thus, further research is needed to examine this issue. Nevertheless, these results may be critical in laying the groundwork for understanding the effectiveness of acute GNS in the treatment of neurogenic detrusor overactivity.

A bioinspired hyperthermic macrophage-based polypyrrole-polyethylenimine (Ppy-PEI) nanocomplex carrier to prevent and disrupt thrombotic fibrin clots.

Fibrinolytic treatments for venous or arterial thrombotic syndromes using systemic administration of thrombolytics, such as streptokinase, can induce life-threatening bleeding complications. In this study, we offer the first proof of concept for a targeted photothermal fibrin clot prevention and reduction technology using macrophages loaded with polypyrrole-polyethylenimine nanocomplexes (Ppy-PEI NCs) and subjected to near-infrared radiation (NIR). We first show that the developed Ppy-PEI NCs could be taken up by defensive macrophages in vitro through endocytosis. The Ppy-PEI NCs generated local hyperthermia upon NIR treatment, which appeared to produce reactive oxygen species in Ppy-PEI NC-loaded macrophages. Preliminary evidence of efficacy as an antithrombotic tool is provided, in vitro, using fibrinogen-converted fibrin clots, and in vivo, in a rat femoral vascular thrombosis model generated by exposure to ferric chloride substance. The in vivo biocompatibility, photothermal behavior, biodistribution, and histological observation of cellular interactions with the Ppy-PEI NCs in the rat model provide rationale in support of further preclinical studies. This Ppy-PEI NC/NIR-based method, which uses a unique macrophage-guided targeting approach to prevent and lyse fibrin clots, may potentially overcome some of the disadvantages of current thrombolytic treatments. STATEMENT OF SIGNIFICANCE: Fibrinolytic treatments for venous or arterial thrombotic syndromes using systemic administration of thrombolytics, such as streptokinase, can induce life-threatening bleeding complications. In this study, we offer the first proof of concept for a targeted photothermal fibrin clot reduction technology using macrophages loaded with polypyrrole-polyethylenimine nanocomplexes (Ppy-PEI NCs) and subjected to near-infrared radiation (NIR). We first show that the developed Ppy-PEI NCs can be taken up by defensive macrophages in vitro through endocytosis. The Ppy-PEI NCs generated local hyperthermia upon NIR treatment, which appeared to produce reactive oxygen species in Ppy-PEI NC-loaded macrophages. Preliminary evidence of efficacy as an antithrombotic tool is provided, in vitro, using fibrinogen-converted fibrin clots, and in vivo, in a rat femoral vascular thrombosis model generated by exposure to ferric chloride substance. The in vivo biocompatibility, photothermal behavior, biodistribution, and histological observation of cellular interactions with the Ppy-PEI NCs in the rat model provide rationale in support of further preclinical studies. This Ppy-PEI NC/NIR-based method, which uses a unique macrophage-guided targeting approach to disintegrate fibrin clots, may potentially overcome some of the disadvantages of current thrombolytic treatments.

Sintered dicalcium pyrophosphate treatment attenuates estrogen deficiency-associated disc degeneration in ovariectomized rats.

BACKGROUND: Estrogen deficiency is associated with musculoskeletal disorders. Sintered dicalcium pyrophosphate (SDCP) is a novel antiosteoporotic agent. In this study, we examined its use for restoration of bone quality and attenuation of disc degeneration in ovariectomy rats. METHODS: Sixty female Sprague Dawley rats were randomly divided into 3 groups, namely sham group undergoing sham surgery, ovariectomy (OVX) group receiving an equivalent volume of isotonic sodium chloride solution, and OVX/SDCP group orally administered with 0.25 mg/mL SDCP. Animals were sacrificed at 3 and 6 months post ovariectomy and lumbar vertebrae and intervertebral discs were harvested. Bone mineral density, micro-computed tomography analysis, and biomechanical testing were performed to assess bone quality. Histological analysis with hematoxylin and eosin, Alcian blue, and Masson's trichrome stain were conducted to determine disc degeneration. Immunohistochemistry and real-time PCR were carried out to measure the expressions of aggrecan, type I collagen, type II collagen, and MMP-1, MMP-3, and MMP-13. RESULTS: SDCP improved bone quality as observed by the results of increased bone mineral density and stiffness in OVX rats. The improvement in disc degeneration induced by estrogen withdrawal was associated with reduced gene expressions of MMPs and increased production of collagen type II. CONCLUSION: SDCP prevents osteoporosis and ameliorates disc degeneration in OVX rats. It represents a favorable therapeutic agent for osteoporotic and osteoarthritic conditions in clinical practice.

A Gelatin Hydrogel-Containing Nano-Organic PEI⁻Ppy with a Photothermal Responsive Effect for Tissue Engineering Applications.

The introduction and designing of functional thermoresponsive hydrogels have been recommended as recent potential therapeutic approaches for biomedical applications. The development of bioactive materials such as thermosensitive gelatin-incorporated nano-organic materials with a porous structure and photothermally triggerable and cell adhesion properties may potentially achieve this goal. This novel class of photothermal hydrogels can provide an advantage of hyperthermia together with a reversibly transformable hydrogel for tissue engineering. Polypyrrole (Ppy) is a bioorganic conducting polymeric substance and has long been used in biomedical applications owing to its brilliant stability, electrically conductive features, and excellent absorbance around the near-infrared (NIR) region. In this study, a cationic photothermal triggerable/guidable gelatin hydrogel containing a polyethylenimine (PEI)⁻Ppy nanocomplex with a porous microstructure was established, and its physicochemical characteristics were studied through dynamic light scattering, scanning electronic microscopy, transmission electron microscopy, an FTIR; and cellular interaction behaviors towards fibroblasts incubated with a test sample were examined via MTT assay and fluorescence microscopy. Photothermal performance was evaluated. Furthermore, the in vivo study was performed on male Wistar rat full thickness excisions model for checking the safety and efficacy of the designed gelatin⁻PEI⁻Ppy nanohydrogel system in wound healing and for other biomedical uses in future. This photothermally sensitive hydrogel system has an NIR-triggerable property that provides local hyperthermic temperature by PEI⁻Ppy nanoparticles for tissue engineering applications. Features of the designed hydrogel may fill other niches, such as being an antibacterial agent, generation of free radicals to further improve wound healing, and remodeling of the promising photothermal therapy for future tissue engineering applications.

Arthroscopic extended rotator interval release for treating refractory adhesive capsulitis.

PURPOSE: To present the clinical results of arthroscopic extended rotator interval release with a stretching program for treating refractory adhesive capsulitis. STUDY DESIGN: Case series; level of evidence, 4. METHODS: Arthroscopy-assisted extended rotator interval tissue release including anterior capsular was performed in 26 patients with refractory adhesive capsulitis. All rotator interval tissues, except the medial sling of the biceps, were excised and the excursion of the subscapularis tendon was restored and freely mobilized. The preoperative mean passive forward flexion was 101°, whereas external rotation at the side was 10°. Patients were followed for a minimum of 2 years and their visual analog scale for pain, muscle power, range of motion, Constant score, modified American Shoulder and Elbow Surgeons Shoulder Evaluation Form score, and modified University of California at Los Angeles score were recorded. RESULTS: Visual pain scale and the aforementioned clinical scores improved postoperatively. The patients exhibited a significant postoperative difference in forward flexion, external rotation, and internal rotation. Postoperative mean passive forward flexion was 172°, whereas external rotation at the side was 58°. There was no difference in the muscle power postoperatively including abduction, internal rotation, and external rotation. CONCLUSIONS: Our study revealed satisfactory subjective and objective clinical results after a 2-year follow-up. Arthroscopy-assisted extended rotator interval release with a stretching program could be an alternative treatment for refractory adhesive capsulitis.

Differentiation Effects of Platelet-Rich Plasma Concentrations on Synovial Fluid Mesenchymal Stem Cells from Pigs Cultivated in Alginate Complex Hydrogel.

This article studied the effects of platelet-rich plasma (PRP) on the potential of synovial fluid mesenchymal stem cells (SF-MSCs) to differentiate. The PRP and SF-MSCs were obtained from the blood and knees of pigs, respectively. The identification of SF-MSCs and their ability to differentiate were studied by histological and surface epitopes, respectively. The SF-MSCs can undergo trilineage mesenchymal differentiation under osteogenic, chondrogenic, and adipocyte induction. The effects of various PRP concentrations (0%, 20% and 50% PRP) on differentiation were evaluated using the SF-MSCs-alginate system, such as gene expression and DNA proliferation. A 50% PRP concentration yielded better differentiation than the 20% PRP concentration. PRP favored the chondrogenesis of SF-MSCs over their osteogenesis in a manner that depended on the ratios of type II collagen/type I collagen and aggrecan/osteopontin. Eventually, PRP promoted the proliferation of SF-MSCs and induced chondrogenic differentiation of SF-MSCs in vitro. Both PRP and SF-MSCs could be feasibly used in regenerative medicine and orthopedic surgeries.