Daily low-intensity pulsed ultrasound stimulation mitigates joint degradation and pain in a post-traumatic osteoarthritis rat model.

Objectives: The aim of this study was to investigate the effects of low-intensity pulsed ultrasound (LIPUS) in a post-traumatic osteoarthritis (OA) rat model and in vitro. Methods: Thirty-eight male, four-month-old Sprague Dawley rats were randomly assigned to Sham, Sham â€‹+ â€‹US, OA, and OA â€‹+ â€‹US. Sham surgery was performed to serve as a negative control, and anterior cruciate ligament transection was used to induce OA. Three days after the surgical procedures, Sham â€‹+ â€‹US and OA â€‹+ â€‹US animals received daily LIPUS treatment, while the rest of the groups received sham ultrasound (US) signals. Behavioral pain tests were performed at baseline and every week thereafter. After 31 days, the tissues were collected, and histological analyses were performed on knees and innervated dorsal root ganglia (DRG) neurons traced by retrograde labeling. Furthermore, to assess the activation of osteoclasts by LIPUS treatment, RAW264.7 â€‹cells were differentiated into osteoclasts and treated with LIPUS. Results: Joint degradation in cartilage and bone microarchitecture were mitigated in OA â€‹+ â€‹US compared to OA. OA â€‹+ â€‹US showed improvements in behavioral pain tests. A significant increase of large soma-sized DRG neurons was located in OA compared to Sham. In addition, a greater percentage of large soma-sized innervated neurons were calcitonin gene-related peptide-positive. Daily LIPUS treatment suppressed osteoclastogenesis in vitro, which was confirmed via histological analyses and mRNA expression. Finally, lower expression of netrin-1, a sensory innervation-related protein, was found in the LIPUS treated cells. Conclusion: Our findings demonstrate that early intervention using LIPUS treatment has protective effects from the progression of knee OA, including reduced tissue degradation, mitigated pain characteristics, improved subchondral bone microarchitecture, and less sensory innervation. Furthermore, daily LIPUS treatment has a suppressive effect on osteoclastogenesis, which may be linked to the suppression of sensory innervation in OA. The translational potential of this article: This study presents a new potential for early intervention in treating OA symptoms through the use of LIPUS, which involves the suppression of osteoclastogenesis and the alteration of DRG profiles. This intervention aims to delay joint degradation and reduce pain.

Evolution from Bioinert to Bioresorbable: In Vivo Comparative Study of Additively Manufactured Metal Bone Scaffolds.

Additively manufactured scaffolds offer significant potential for treating bone defects, owing to their porous, customizable architecture and functionalization capabilities. Although various biomaterials have been investigated, metals - the most successful orthopedic material - have yet to yield satisfactory results. Conventional bio-inert metals, such as titanium (Ti) and its alloys, are widely used for fixation devices and reconstructive implants, but their non-bioresorbable nature and the mechanical property mismatch with human bones limit their application as porous scaffolds for bone regeneration. Advancements in additive manufacturing have facilitated the use of bioresorbable metals, including magnesium (Mg), zinc (Zn), and their alloys, as porous scaffolds via Laser Powder Bed Fusion (L-PBF) technology. This in vivo study presents a comprehensive, side-by-side comparative analysis of the interactions between bone regeneration and additively manufactured bio-inert/bioresorbable metal scaffolds, as well as their therapeutic outcomes. The research offers an in-depth understanding of the metal scaffold-assisted bone healing process, illustrating that Mg and Zn scaffolds contribute to the bone healing process in distinct ways, but ultimately deliver superior therapeutic outcomes compared to Ti scaffolds. These findings suggest that bioresorbable metal scaffolds hold considerable promise for the clinical treatment of bone defects in the near future.

Bioactive superparamagnetic iron oxide-gold nanoparticles regulated by a dynamic magnetic field induce neuronal Ca2+ influx and differentiation.

Treating neurodegenerative diseases, e.g., Alzheimer's Disease, remains a significant challenge due to the limited neuroregeneration rate in the brain. The objective of this study is to evaluate the hypothesis that external magnetic field (MF) stimulation of nerve growth factor functionalized superparamagnetic iron oxide-gold (NGF-SPIO-Au) nanoparticles (NPs) can induce Ca2+ influx, membrane depolarization, and enhance neuron differentiation with dynamic MF (DMF) outperforming static MF (SMF) regulation. We showed the that total intracellular Ca2+ influx of PC-12 cells was improved by 300% and 535% by the stimulation of DMF (1 Hz, 0.5 T, 30min) with NGF-SPIO-Au NPs compared to DMF alone and SMF with NGF-SPIO-Au NPs, respectively, which was attributed to successive membrane depolarization. Cellular uptake performed with the application of sodium azide proved that DMF enhanced cellular uptake of NGF-SPIO-Au NPs via endocytosis. In addition, DMF upregulated both the neural differentiation marker (ß3-tubulin) and the cell adhesive molecule (integrin-ß1) with the existence of NGF-SPIO-Au NPs, while SMF did not show these effects. The results imply that noninvasive DMF-stimulated NPs can regulate intracellular Ca2+ influx and enhance neuron differentiation and neuroregeneration rate.

Blending with transition metals improves bioresorbable zinc as better medical implants.

Zinc (Zn) is a new class of bioresorbable metal that has potential for cardiovascular stent material, orthopedic implants, wound closure devices, etc. However, pure Zn is not ideal for these applications due to its low mechanical strength and localized degradation behavior. Alloying is the most common/effective way to overcome this limitation. Still, the choice of alloying element is crucial to ensure the resulting alloy possesses sufficient mechanical strength, suitable degradation rate, and acceptable biocompatibility. Hereby, we proposed to blend selective transition metals (i.e., vanadium-V, chromium-Cr, and zirconium-Zr) to improve Zn's properties. These selected transition metals have similar properties to Zn and thus are beneficial for the metallurgy process and mechanical property. Furthermore, the biosafety of these elements is of less concern as they all have been used as regulatory approved medical implants or a component of an implant such as Ti6Al4V, CoCr, or Zr-based dental implants. Our study showed the first evidence that blending with transition metals V, Cr, or Zr can improve Zn's properties as bioresorbable medical implants. In addition, three in vivo implantation models were explored in rats: subcutaneous, aorta, and femoral implantations, to target the potential clinical applications of bioresorbable Zn implants.

Progress, Opportunities, and Challenges of Magneto-Plasmonic Nanoparticles under Remote Magnetic and Light Stimulation for Brain-Tissue and Cellular Regeneration.

Finding curable therapies for neurodegenerative disease (ND) is still a worldwide medical and clinical challenge. Recently, investigations have been made into the development of novel therapeutic techniques, and examples include the remote stimulation of nanocarriers to deliver neuroprotective drugs, genes, growth factors, and antibodies using a magnetic field and/or low-power lights. Among these potential nanocarriers, magneto-plasmonic nanoparticles possess obvious advantages, such as the functional restoration of ND models, due to their unique nanostructure and physiochemical properties. In this review, we provide an overview of the latest advances in magneto-plasmonic nanoparticles, and the associated therapeutic approaches to repair and restore brain tissues. We have reviewed their potential as smart nanocarriers, including their unique responsivity under remote magnetic and light stimulation for the controlled and sustained drug delivery for reversing neurodegenerations, as well as the utilization of brain organoids in studying the interaction between NPs and neuronal tissue. This review aims to provide a comprehensive summary of the current progress, opportunities, and challenges of using these smart nanocarriers for programmable therapeutics to treat ND, and predict the mechanism and future directions.

Improved mechanical, degradation, and biological performances of Zn-Fe alloys as bioresorbable implants.

Zinc (Zn) is a promising bioresorbable implant material with more moderate degradation rate compared to magnesium (Mg) and iron (Fe). However, the low mechanical strength and localized degradation behavior of pure Zn limit its clinical applications. Alloying is one of the most effective ways to overcome these limitations. After screening the alloying element candidates regarding their potentials for improvement on the degradation and biocompatibility, we proposed Fe as the alloying element for Zn, and investigated the in vitro and in vivo performances of these alloys in both subcutaneous and femoral tissues. Results showed that the uniformly distributed secondary phase in Zn-Fe alloys significantly improved the mechanical property and facilitated uniform degradation, which thus enhanced their biocompatibility, especially the Zn-0.4Fe alloy. Moreover, these Zn-Fe alloys showed outstanding antibacterial property. Taken together, Zn-Fe alloys could be promising candidates as bioresorbable medical implants for various cardiovascular, wound closure, and orthopedic applications.

Biomechanical Comparison of Krackow Repair and Percutaneous Achilles Repair System for Achilles Tendon Rupture Fixation: A Cadaveric and Finite Element Analysis Study.

Background: Open and percutaneous repair surgeries are widely used for the Achilles tendon rupture. However, prior biomechanic studies of these 2 approaches have mixed conclusions; therefore, we designed a cadaver and finite element (FE) model biomechanical study to compare the mechanical differences between the percutaneous Achilles repair system (PARS) and Krackow open repair under tensile load and rotation. Methods: Sixteen Achilles tendons were extracted from fresh-frozen cadaver ankles and the calcaneums were fixed in mortar. A force control dynamic tensile mechanical test was performed at 1 Hz with 30- and 100-N cyclic loads. Initial intact baseline testing was followed by an incision on all Achilles tendons, 4 cm from the calcaneus insertion, which were then repaired using the PARS (n = 8) or Krackow (n = 8) method. Recorded force-displacement values were used to calculate mechanical parameters, and statistical significance of differences was determined by unpaired (between repair techniques) and paired (intact vs repaired) t tests. Material properties of the Achilles tendon in the FE model were modified and a 10-Nm flexion was simulated for intact and surgical groups. Results: No differences were found between intact tendons assigned to PARS or Krackow repairs in Young's modulus (P = .582) and stiffness (P = .323). Pre- and postoperative Young's modulus was significantly decreased for both groups (Intact 230.60±100.76 MPa vs PARS 142.44±37.37 MPa, P < .012; Intact 207.46±81.12 MPa vs Krackow109.43±27.63 MPa, P < .002). Stiffness decreased significantly after surgery for both groups (Intact 25.33±10.89 N/mm vs PARS 6.51±1.68 N/mm, P < .003; Intact 20.30±8.65 N/mm vs Krackow 5.97±1.30 N/mm, P < .003). PARS ultimate tensile strength was significantly higher than the Krackow (PARS 280.29±47.32 N vs Krackow 196.97±54.28 N, P < .003) but not significantly different in the ultimate tensile strain. PARS had a significantly lower postoperative gap compared to Krackow (PARS 9.75±5.87 mm vs Krackow 25.19±7.72 mm, P < .001). FE analysis predicted an increased talocalcaneal contact pressure, maximum principal stress, and rotation in the Krackow vs PARS models, respectively. Conclusion: Biomechanical parameters observed in this study through mechanical testing and FE analysis favor the selection of PARS over the Krackow repair based on better strength, higher failure force, and lower gap generation.Clinical Relevance: The study has analyzed two Achilles tendon repair methods using cadaver and numerical estimation and may help clinicians gain insight into selection of tendon repair approaches to generate better clinical outcomes.

A universal post-treatment strategy for biomimetic composite hydrogel with anisotropic topological structure and wide range of adjustable mechanical properties.

The development of biomimetic materials with anisotropic topological structure and wide range of adjustable mechanical properties is central to tissue engineering fields. In this work, on the basis of a stiff/stretchable dually crosslinked hydrogel, we paid more attention to the synergistic contribution of the confined drying and re-swelling (CDR) effect and Hofmeister effect to its micro structures, polymer aggregation states and mechanical strength. Specifically, by changing the pre-strains of the CDR procedure and the soaking time during the salting-out procedure, the arrangement structure orientation, chain-entanglement density, and supramolecular interaction strength within the polymer can be adjusted by changing the processing sequence of the two procedures, so that to obtain anisotropic biomimetic hydrogels with adjustable mechanical properties in a wide range. Thus, this engineered anisotropic polymer can mimic the natural tissues' mechanical properties in regeneration. Moreover and importantly, these anisotropic hydrogels exhibit prominent self-recovery properties. In summary, with the integration of molecular and structural engineering approaches, this study presents a universal strategy for developing anisotropic hydrogels, which could be widely used as biomimetic substitutes with anisotropic features in tissue regeneration.

Longitudinal Intravital Imaging Through Clear Silicone Windows.

Intravital microscopy (IVM) enables visualization of cell movement, division, and death at single-cell resolution. IVM through surgically inserted imaging windows is particularly powerful because it allows longitudinal observation of the same tissue over days to weeks. Typical imaging windows comprise a glass coverslip in a biocompatible metal frame sutured to the mouse's skin. These windows can interfere with the free movement of the mice, elicit a strong inflammatory response, and fail due to broken glass or torn sutures, any of which may necessitate euthanasia. To address these issues, windows for long-term abdominal organ and mammary gland imaging were developed from a thin film of polydimethylsiloxane (PDMS), an optically clear silicone polymer previously used for cranial imaging windows. These windows can be glued directly to the tissues, reducing the time needed for insertion. PDMS is flexible, contributing to its durability in mice over time-up to 35 days have been tested. Longitudinal imaging is imaging of the same tissue region during separate sessions. A stainless-steel grid was embedded within the windows to localize the same region, allowing the visualization of dynamic processes (like mammary gland involution) at the same locations, days apart. This silicone window also allowed monitoring of single disseminated cancer cells developing into micro-metastases over time. The silicone windows used in this study are simpler to insert than metal-framed glass windows and cause limited inflammation of the imaged tissues. Moreover, embedded grids allow for straightforward tracking of the same tissue region in repeated imaging sessions.

Piezo1 channel activation in response to mechanobiological acoustic radiation force in osteoblastic cells.

Mechanobiological stimuli, such as low-intensity pulsed ultrasound (LIPUS), have been shown to promote bone regeneration and fresh fracture repair, but the fundamental biophysical mechanisms involved remain elusive. Here, we propose that a mechanosensitive ion channel of Piezo1 plays a pivotal role in the noninvasive ultrasound-induced mechanical transduction pathway to trigger downstream cellular signal processes. This study aims to investigate the expression and role of Piezo1 in MC3T3-E1 cells after LIPUS treatment. Immunofluorescence analysis shows that Piezo1 was present on MC3T3-E1 cells and could be ablated by shRNA transfection. MC3T3-E1 cell migration and proliferation were significantly increased by LIPUS stimulation, and knockdown of Piezo1 restricted the increase in cell migration and proliferation. After labeling with Fluo-8, MC3T3-E1 cells exhibited fluorescence intensity traces with several high peaks compared with the baseline during LIPUS stimulation. No obvious change in the fluorescence intensity tendency was observed after LIPUS stimulation in shRNA-Piezo1 cells, which was similar to the results in the GsMTx4-treated group. The phosphorylation ratio of ERK1/2 in MC3T3-E1 cells was significantly increased (P < 0.01) after LIPUS stimulation. In addition, Phalloidin-iFluor-labeled F-actin filaments immediately accumulated in the perinuclear region after LIPUS stimulation, continued for 5 min, and then returned to their initial levels at 30 min. These results suggest that Piezo1 can transduce LIPUS-induced mechanical signals into intracellular calcium. The influx of Ca2+ serves as a second messenger to activate ERK1/2 phosphorylation and perinuclear F-actin filament polymerization, which regulate the proliferation of MC3T3-E1 cells.

Longitudinal effects of low-intensity pulsed ultrasound on osteoporosis and osteoporotic bone defect in ovariectomized rats.

Low-intensity pulsed ultrasound (LIPUS) with an intensity (spatial average temporal average, ISATA) of 30 mW/cm2 has been widely proved to be effective on impaired bone healing, but showing little effectiveness in the treatment of osteoporosis. We hypothesized that the intensity of LIPUS may be a key factor in explaining this difference, thus two intensity levels, the widely used 30 mW/cm2 and a higher 150 mW/cm2, were used to simultaneously treat osteoporosis and osteoporotic bone defect in ovariectomized (OVX) rats with a 1-mm drill hole on their left femurs.Results showed that 150 mW/cm2 LIPUS augmented the healing rate of the drill hole than 30 mW/cm2 after 3-week LIPUS treatment, although did not further enhance the healing rate after 6-week LIPUS treatment. For ameliorating osteoporosis, 150 mW/cm2 LIPUS achieved more advantages over 30 mW/cm2 in improving bone density, microstructure and biomechanics 6 weeks after LIPUS intervention. In conclusion, LIPUS with an intensity of 30 mW/cm2 was sufficient to facilitate bone defect healing, but a higher intensity can be considered as a rapid trigger for osteoporotic bone repair. In addition, improving the intensity of LIPUS may be a potentially effective consideration for alleviation of osteoporosis, and the LIPUS regimen in the treatment of osteoporosis remains to be optimized.

Evaluation of nucleus pulposus fluid velocity and pressure alteration induced by cartilage endplate sclerosis using a poro-elastic finite element analysis.

The nucleus pulposus (NP) in the intervertebral disk (IVD) depends on diffusive fluid transport for nutrients through the cartilage endplate (CEP). Disruption in fluid exchange of the NP is considered a cause of IVD degeneration. Furthermore, CEP calcification and sclerosis are hypothesized to restrict fluid flow between the NP and CEP by decreasing permeability and porosity of the CEP matrix. We performed a finite element analysis of an L3-L4 lumbar functional spine unit with poro-elastic constitutive equations. The aim of the study was to predict changes in the solid and fluid parameters of the IVD and CEP under structural changes in CEP. A compressive load of 500 N was applied followed by a 10 Nm moment in extension, flexion, lateral bending, and axial rotation to the L3-L4 model with fully saturated IVD, CEP, and cancellous bone. A healthy case of L3-L4 physiology was then compared to two cases of CEP sclerosis: a calcified cartilage endplate and a fluid constricted sclerotic cartilage endplate. Predicted NP fluid velocity increased for the calcified CEP and decreased for the calcified + less permeable CEP. Decreased NP fluid velocity was prominent in the axial direction through the CEP due to a less permeable path available for fluid flux. Fluid pressure and maximum principal stress in the NP were predicted to increase in both cases of CEP sclerosis compared to the healthy case. The porous medium predictions of this analysis agree with the hypothesis that CEP sclerosis decreases fluid flow out of the NP, builds up fluid pressure in the NP, and increases the stress concentrations in the NP solid matrix.

Calcium phosphate coatings enhance biocompatibility and degradation resistance of magnesium alloy: Correlating in vitro and in vivo studies.

Magnesium (Mg) and its alloys are promising biodegradable materials for orthopedic applications. However, one of the major problems is their rapid degradation rate with quick evolution of hydrogen gas. To overcome this problem, calcium phosphate (CaP) coatings have been used to improve the degradation resistance and the biocompatibility of Mg materials. This study focuses on the comparison and correlation of the in vitro and in vivo degradation and biocompatibility behaviors of these materials. A CaP coating consisting of dicalcium phosphate dihydrate (DCPD) was deposited on an AZ60 Mg alloy by the chemical conversion method. Then, the in vitro degradation testing including electrochemical and immersion tests, and in vivo implantation of the CaP coated Mg alloy were conducted to compare the degradation behaviors. Next, the in vitro cell behavior and in vivo bone tissue response were also compared on both uncoated and CaP-coated Mg samples. Data showed that the CaP coating provided the Mg alloy with significantly better biodegradation behavior and biocompatibility. The in vitro and in vivo biocompatibility tests exhibited good consistency while not the case for biodegradation. Results showed that the in vitro electrochemical test could be a quick screening tool for the biodegradation rate, while the in vitro immersion degradation rate was often 2-4 folds faster than the in vivo degradation rate.

Porous tantalum rod implantation is associated with low survival rates in patients with type C2 osteonecrosis of the femoral head but has no effect on the clinical outcome of conversion total hip arthroplasty: a retrospective study with an average 8-year follow-up.

BACKGROUND: Our study aimed to investigate the clinical outcomes and survival rates following porous tantalum rod surgery (PTRS) and conversion total hip arthroplasty (THA) subsequent to failed PTRS. METHODS: A total of 38 subjects (40 hips) with osteonecrosis of the femoral head (ONFH) were included in this retrospective study between January 2008 and December 2011. All subjects were evaluated before surgery by using the Association Research Circulation Osseous (ARCO) classification system, the Japan Investigation Committee (JIC) classification and the Harris hip score (HHS). The endpoint of this study was set as final follow-up (including the survival time of PTRS and conversion THA). The rates of radiological progression were also evaluated. Patients who received conversion THA were further followed and compared to a control group of 58 patients with ONFH who underwent primary THA. RESULTS: The mean follow-up time was 120.7 ± 9.2 (range, 104-143) months, and the overall survival rate was 75% at 96 months (ARCO stage II: 81.5%; stage III: 38.5%; JIC type C1: 83.3%; C2: 30%). The HHS before surgery was 59 (55-61), in contrast to 94 (91-96) at 96 months follow-up (P < 0.01). HHS in stage III show a significant poorer result compared to stage II at 24 months. HHS in Type C2 group show no significant difference compared to HHS before surgery at 24 and 60 months follow up (P = 0.91, P = 0.30). Twelve hips requiring secondary THA were followed for 66.9 ± 31.7 months, and control hips that underwent primary THA was followed for 75.4 ± 14.9 months. The HHS in the conversion group was 89 (86-93) and that in the primary THA group was 92 (79-95, P = 0.09) at the 5-year follow-up. CONCLUSION: In the mid-term follow-up, porous tantalum implants showed an encouraging survival rate in symptomatic patients in early stages (ARCO stage II) or with limited necrotic lesions (JIC type C1). In addition, our results did not demonstrated any difference between primary THA and conversion THA.

Osteoclastic activity was associated with the development of steroid-induced osteonecrosis of femoral head.

This study is focussed on evaluating and comparing two mediators of osteoclast, osteoprotegerin (OPG) and nuclear factor-κB ligand (RANKL), in plasma and tissue levels in patients with steroid-induced osteonecrosis of femoral head (SIONFH). Subjects were included in this cross-sectional case-control study in 2016. Bone histomorphology, immunohistochemistry, Western blotting, OPG and RANKL plasma levels, post-hoc statistical power and receiver-operating characteristic (ROC) curves were evaluated. Eighty-six patients diagnosed with SIONFH and 51 healthy subjects were included. OPG expression levels in bone samples increased with ARCO stage, and RANKL expression levels decreased with ARCO stages. Plasma OPG and RANKL levels were significantly higher in the SIONFH group compared with the healthy control group. The plasma OPG level and ratio of OPG and RANKL were positively associated with ARCO stages and significantly higher in stages III and IV. Plasma RANKL levels were negatively associated with ARCO stage and were significantly higher in ARCO stages II and III. Plasma OPG and RANKL may represent potential biomarkers during SIONFH at different stages. Higher plasma OPG levels indicated late-stage SIONFH, and higher plasma RANKL levels indicated early stage. Our findings may provide a clue for the development of diagnostic tools and therapies for SIONFH.

Porous zinc scaffolds for bone tissue engineering applications: A novel additive manufacturing and casting approach.

As a degradable metal, zinc (Zn) has attracted an immense amount of interest as the next generation of bioresorbable implants thanks to its modest corrosion rate and its vital role in bone remodeling, yet very few studies have thoroughly investigated its functionality as a porous implant for bone tissue engineering purposes. Zn bone scaffolds with two different pore sizes of 900 µm and 2 mm were fabricated using additive manufacturing-produced templates combined with casting. The compressive properties, corrosion rates, biocompatibility, and antibacterial performance of the bioscaffolds were examined and compared to a non-porous control. The resulting textured and porous Zn scaffolds exhibit a fully interconnected pore structure with precise control over topology. As pore size and porosity increased, mechanical strength decreased, and corrosion rate accelerated. Cell adhesion and growth on scaffolds were enhanced after an ex vivo pretreatment method. In vitro cellular tests confirmed good biocompatibility of the scaffolds. As porosity increased, potent antibacterial rates were also observed. Taken together, these results demonstrate that Zn porous bone scaffolds are promising for orthopedic applications.

Low-intensity pulsed ultrasound protects subchondral bone in rabbit temporomandibular joint osteoarthritis by suppressing TGF-ß1/Smad3 pathway.

Transforming growth factor ß1(TGF-ß1)/Smad3 pathway promotes the pathological progression of subchondral bone in osteoarthritis. The aim of this study is to determine the effect of low-intensity pulsed ultrasound (LIPUS) on the pathological progression and TGF-ß1/Smad3 pathway of subchondral bone in temporomandibular joint osteoarthritis (TMJOA). Rabbit TMJOA model was established by type II collagenase induction. The left joint in this model was continuously stimulated with LIPUS for 3 and 6 weeks (1 MHz; 30 mW/cm2 ) for 20 min/day. The morphological and histological features of subchondral bone were respectively examined by microcomputed tomography and Safranin-O staining. The number of osteoclasts was quantitatively assessed by tartrate-resistant acid phosphatase staining. Immunohistochemistry and Western blot analysis were conducted to evaluate the protein expression of Cathepsin K and TGF-ß1/Smad3 pathway. The results indicated that LIPUS could improve the trabecular microstructure and histological characteristics of subchondral bone in rabbit TMJOA. It also suppressed abnormal subchondral bone resorption and activation of TGF-ß1/Smad3 pathway, characterized by the number of osteoclasts, protein expression levels of Cathepsin K, TGF-ß1, type II TGFß receptor, and phosphorylated Smad3 (pSmad3) were decreased. In conclusion, LIPUS promoted the quality of subchondral bone by suppressing osteoclast activity and TGF-ß1/Smad3 pathway in rabbit TMJOA.

Evolution of metallic cardiovascular stent materials: A comparative study among stainless steel, magnesium and zinc.

A cardiovascular stent is a small mesh tube that expands a narrowed or blocked coronary artery. Unfortunately, current stents, regardless metallic or polymeric, still largely fall short to the ideal clinical needs due to late restenosis, thrombosis and other clinical complications. Nonetheless, metallic stents are preferred clinically thanks to their superior mechanical property and radiopacity to their polymeric counterparts. The emergence of bioresorbable metals opens a window for better stent materials as they may have the potential to reduce or eliminate late restenosis and thrombosis. In fact, some bioresorbable magnesium (Mg)-based stents have obtained regulatory approval or under trials with mixed clinical outcomes. Some major issues with Mg include the too rapid degradation rate and late restenosis. To mitigate these problems, bioresorbable zinc (Zn)-based stent materials are being developed lately with the more suitable degradation rate and better biocompatibility. The past decades have witnessed the unprecedented evolution of metallic stent materials from first generation represented by stainless steel (SS), to second generation represented by Mg, and to third generation represented by Zn. To further elucidate their pros and cons as metallic stent materials, we systematically evaluated their performances in vitro and in vivo through direct side-by-side comparisons. Our results demonstrated that tailored Zn-based material with proper configurations could be a promising candidate for a better stent material in the future.

Therapeutic Effects of Low-Intensity Pulsed Ultrasound on Osteoporosis in Ovariectomized Rats: Intensity-Dependent Study.

This study investigated the effects of low-intensity pulsed ultrasound (LIPUS) of different spatial-average-temporal-average intensity (ISATA) ranging from 15-150 mW/cm2 on the treatment of osteoporosis in ovariectomized rats. Healthy 3-mo-old female Sprague-Dawley rats were randomly divided into nine groups (n = 12 per group): sham-ovariectomy (OVX) control group, OVX control group and OVX groups treated with LIPUS at seven different intensities (ISATA: 15, 30, 50, 75, 100, 125 and 150 mW/cm2, respectively). LIPUS was applied to bilateral femurs 12 wk post-OVX for 20 min/d for 6 wk. Micro-computed tomography, biomechanical tests, serum biochemical analysis and grip strength tests were performed to evaluate the therapeutic effects of LIPUS at different intensities. Results revealed that LIPUS intensity yielded strong correlations with bone mineral density and bone microstructure (R2 = 0.57-0.83) and bone mechanical strength (R2 = 0.80-0.97), and that the intensity of 150 mW/cm2, instead of the 30 mW/cm2 widely used in bone fracture healing, was most effective in maintaining bone mass among all the LIPUS signals between 15 and 150 mW/cm2. This suggests that higher ultrasound intensity (i.e., 150 mW/cm2) may be more effective than lower intensity in mitigation of osteopenia and osteoporosis.

Mechanobiological modulation of in situ and in vivo osteocyte calcium oscillation by acoustic radiation force.

The biological effect of ultrasound on bone regeneration has been well documented, yet the underlying mechanotransduction mechanism is largely unknown. In relation to the mechanobiological modulation of the cytoskeleton and Ca2+ influx by short-term focused acoustic radiation force (FARF), the current study aimed to visualize and quantify Ca2+ oscillations in real-time of in situ and in vivo osteocytes in response to focused low-intensity pulsed ultrasound (FLIPUS). For in situ studies, fresh mice calvaria were subjected to FLIPUS stimulation at 0.05, 0.2, 0.3, and 0.7 W. For the in vivo study, 3-month-old C57BL/6J Ai38/Dmp1-Cre mice were subjected to FLIPUS at 0.15, 1, and 1.5 W. As observed via real-time confocal imaging, in situ FLIPUS led to more than 80% of cells exhibiting Ca2+ oscillations at 0.3-0.7 W and led to a higher number of Ca2+ spikes with larger values at >0.3 W. In vivo FLIPUS at 1-1.5 W led to more than 90% of cells exhibiting Ca2+ oscillations. Higher FLIPUS energies led to larger Ca2+ spike magnitudes. In conclusion, this study provided a pilot study of both in situ and in vivo osteocytic Ca2+ oscillations under noninvasive FARF, which aids further exploration of the mechanosensing mechanism of the controlled bone cell motility response to the stimulus.