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.

Calcium peroxide aids tyramine-alginate gel to crosslink with tyrosinase for efficient cartilage repair.

The innate cartilage extracellular matrix is avascular and plays a vital role in innate chondrocytes. Recapping the crucial components of the extracellular matrix in engineered organs via polymeric gels and bioinspired approaches is promising for improving the regenerative aptitude of encapsulated cartilage/chondrocytes. Conventional gel formation techniques for polymeric materials rely on employing oxidative crosslinking, which is constrained in this avascular environment. Further, poor mechanical properties limit the practical applications of polymeric gels and reduce their therapeutic efficacy. Herein, the purpose of this study was to develop a bioadhesive gel possessing dual crosslinking for engineering cartilage. Tyramine (TYR) was first chemically conjugated to the alginate (ALG) backbone to form an ALG-TYR precursor, followed by the addition of calcium peroxide (CaO2); calcium ions of CaO2 physically crosslink with ALG, and oxygen atoms of CaO2 chemically crosslink TYR with tyrosinase, thus enabling dual/enhanced crosslinking and possessing injectability. The ALG-TYR/tyrosinase/CaO2 gel system was chemically, mechanically, cellularly, and microscopically characterized. The gel system developed herein was biocompatible and showed augmented mechanical strength. The results showed, for the first time, that CaO2 supplementation preserved cell viability and enhanced the crosslinking ability, bioadhesion, mechanical strength, chondrogenesis, and stability for cartilage regeneration.

Strontium ranelate-laden near-infrared photothermal-inspired methylcellulose hydrogel for arthritis treatment.

Rheumatoid arthritis (RA) is of foremost concern among long-term autoimmune disorders, as it leads to inflammation, exudates, chondral degeneration, and painful joints. Because RA severity often fluctuates over time, a local drug delivery method that titrates release of therapeutics to arthritis bioactivity should represent a promising paradigm of RA therapy. Given the local nature of RA chronic illnesses, polysaccharide-drug delivering systems have the promise to augment therapeutic outcomes by offering controlled release of bioactive materials, diminishing the required frequency of administration, and preserving therapeutic levels in affected pathological regions. Herein, an intra-articular photothermal-laden injectable methylcellulose (MC) polymeric hydrogel carrier incorporating strontium ranelate (SrR) and sodium chloride was investigated to resolve these issues. Physicochemical and cellular characteristics of the MC carrier system were thoroughly evaluated. The slow release of SrR, enhancement of the material mechanical strength, and the potential of the non-invasive near-infrared photothermal gel to improve blood circulation and suppress inflammation in a mini-surgical model of RA were examined. Biocompatibility and suppression of intracellular ROS-induced inflammation were observed. This multifunctional photothermal MC hydrogel carrier is anticipated to be an alternative approach for future orthopedic disease treatment.

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.

Effect of hyperbaric oxygenation on intervertebral disc degeneration: an in vivo study with sprague-dawley rats.

STUDY DESIGN: An in vivo study was conducted to test the effect of hyperbaric oxygenation (HBO) on intervertebral disc degeneration in Sprague-Dawley rats. OBJECTIVE: To observe the changes in intervertebral disc height and levels of glycosaminoglycan, collagen, interleukin-1ß (IL-1ß), prostaglandin E2 (PGE2), and inducible nitric oxide synthase (iNOS) in degenerated intervertebral discs after HBO therapy. SUMMARY OF BACKGROUND DATA: Although the involvement of IL-1ß, PGE-2, NO, and low O2 concentration has been demonstrated in intervertebral disc degeneration, the actual mechanism is not clear. It has been reported that HBO influences changes in IL-1ß, PGE-2, NO, and O2 concentration. Previously, a study demonstrated an in vitro positive effect of HBO on the human nucleus pulposus. Thus, an in vivo study in animals was necessary. METHODS: Twelve Sprague-Dawley rats were each injected with chondroitinase ABC in 2 proximal intervertebral discs of the tail. After treating with 100% oxygen at 2.5 atmospheres 2 hours per days for 10 days, the change in disc height was determined by radiography. The amounts of PGE-2, iNOS, glycosaminoglycan, and total collagen in the intervertebral disc were quantified by enzyme-linked immunosorbent assay. Tissue morphology and the distribution of glycosaminoglycan, IL-1ß, and iNOS in the intervertebral disc were assessed by histology and immunohistochemistry. The area of IL-1ß in the intervertebral discs was quantified using image analysis software. RESULTS: HBO therapy stopped the decrease in intervertebral disc height, caused an increase in the amount of glycosaminoglycan, and inhibited IL-1ß, PGE-2, and iNOS production. CONCLUSION: HBO provides a potential treatment modality for intervertebral disc degeneration.

Effect of hyperbaric oxygenation on intervertebral disc degeneration: an in vitro study with human lumbar nucleus pulposus.

STUDY DESIGN: An in vitro study with degenerated human lumbar intervertebral disc specimens cultured under hyperbaric oxygenation (HBO). OBJECTIVE: To observe the changes in interleukin (IL)-1ß, prostaglandin (PG)-E2, nitric oxide (NO), cell growth, and apoptosis of the human nucleus pulposus cell (NPC) after HBO. SUMMARY OF BACKGROUND DATA: Intervertebral disc degeneration has been demonstrated as related to IL-1ß, PG-E2, NO, and O2 concentration but the actual mechanism is not clear. HBO also has also been reported in the literature to influence changes in IL-1ß, prostaglandin E2, NO, and O2 concentration. However, the direct effect of HBO on the disc cells has not been previously reported. METHODS: We collected 12 human lumbar degenerated disc specimens and evaluated the effects of HBO on the cultured NPCs. The amounts of IL-1ß, PG-E2, and NO in the conditioned medium were quantified by enzyme-linked immunosorbent assay and high performance liquid chromatography. Cell growth was measured by increase in cell number. Cell viability and proteoglycan content were evaluated by histologic study using safranin O staining. In situ analysis of apoptosis was performed using Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. RESULTS: Our data indicated that HBO treatment inhibited IL-1ß, PG-E2, and NO production but increased cell number and matrix synthesis of cultured NPCs. TUNEL staining showed that HBO treatment suppressed the apoptosis of cultured NPCs. CONCLUSION: HBO provides a potential treatment modality for disc degeneration.

The effect of hyperbaric oxygen therapy on spinal fusion: using the model of posterolateral intertransverse fusion in rabbits.

BACKGROUND: The purpose of this study is to evaluate the facilitating effect of hyperbaric oxygen (HBO) on posterolateral intertransverse fusion using a validated rabbit model. METHODS: Twenty-four male New Zealand rabbits underwent posterolateral intertransverse fusion at L5-L6 with autogenous iliac bone graft. They were evenly divided into two groups: the HBO group and the normal room air (RA) group. Each group had six rabbits killed at 4 weeks and 8 weeks, respectively. The rabbits in the HBO groups were treated with 100% oxygen at 2.5 atm for 2 hours a day. After being killed, all rabbits were subjected to radiographic examination, manual testing, and torsional loading to evaluate the results of spinal fusion. RESULT: Radiographic union of intertransverse fusion areas at 4-week RA, 4-week HBO, 8-week RA, and 8-week HBO were 2 of 12, 7 of 12, 7 of 12, and 10 of 12, respectively. Solid union proven by manual palpation was found to be zero of six, three of six, four of six, and five of six of the cases, respectively. The average peak torsional momentums were 2120.2, 2576.5, 2661.6, and 3079.8 N-mm, respectively. Spinal fusion was significantly improved in the HBO groups at both 4 weeks and 8 weeks. CONCLUSION: The results of this study suggest that intermittent hyperbaric oxygen therapy will hasten the bone healing process and improve the fusion rate as compared with the non-HBO group.