Subcutaneous Implantation Research Articles

Silver nanoparticles can be sampled by ultrafiltration probe but elution into & recovery from plasma and Dulbecco's Phosphate Buffered Saline differs in vitro.

Locally sustained release antimicrobials such as silver nanoparticles (AgNPs) might prove useful in combating local infections. Their elution has been investigated in Phosphate Buffered Saline (PBS) including from poloxamer 407 (P407). No information exists on possible interactions with proteins, nor have ultrafiltration (UF) probes been evaluated to measure Ag. These investigations would provide helpful data prior to investigating the sustained release after subcutaneous implantation in vivo over time. We compared (1) the influence of elution fluid on AgNP elution, and (2) UF probe and direct sampling in vitro. Six AgNP-P407 specimens in a dialysis tube were placed in Dulbecco's PPBS (DPBS) (n = 3) or canine plasma (n = 3) for 96 h on a stirred hot plate (37 °C and 600 rpm) and sampled 20 times. A 0.001 mg/mL AgNP solution was prepared in DPBS or plasma. Six pipette and UF probe samples were taken of each. Inductively coupled plasma mass spectrometry was used to analyze Ag. Stock plasma contained Ag. At 96 h, 5/6 dialysis tubes had not fully released AgNP. One peak in hourly Ag increase was present in DPBS (10-13 h), and two peaks in plasma (6-8 and 10-13 h). The hourly Ag increase in plasma decreased earlier than in DPBS. Ultrafiltration probe sampling was possible in both DPBS and plasma and resulted in higher Ag concentrations but with more variation. While in vitro use of DPBS might be more cost effective, plasma should be considered due to difference in elution and recovery. Ultrafiltration probes can be used to sample Ag, but results will have a greater degree of variation, and multiple samples and increased time points should be considered.

Double crosslinking decellularized bovine pericardium of dialdehyde chondroitin sulfate and zwitterionic copolymer for bioprosthetic heart valves with enhanced antithrombogenic, anti-inflammatory and anti-calcification properties.

Due to the increasing aging population and the advancements in transcatheter aortic valve replacement (TAVR), the use of bioprosthetic heart valves (BHVs) in patients diagnosed with valvular disease has increased substantially. Commercially available glutaraldehyde (GA) cross-linked biological valves suffer from reduced durability due to a combination of factors, including the high cell toxicity of GA, subacute thrombus, inflammation and calcification. In this study, oxidized chondroitin sulfate (OCS), a natural polysaccharide derivative, was used to replace GA to cross-link decellularized bovine pericardium (DBP), carrying out the first crosslinking of DBP to obtain OCS-BP. Subsequently, the zwitterion radical copolymerization system was introduced in situ to perform double cross-linking to obtain double crosslinked BHVs with biomimetic modification (P(APM/MPC)-OCS-BP). P(APM/MPC)-OCS-BP presented enhanced mechanical properties, collagen stability and enzymatic degradation resistance due to double crosslinking. The ex vivo AV-shunt assay and coagulation factors test suggested that P(APM/MPC)-OCS-BP exhibited excellent anticoagulant and antithrombotic properties due to the introduction of P(APM/MPC). P(APM/MPC)-OCS-BP also showed good HUVEC-cytocompatibility due to the substantial reduction of its residual aldehyde group. The subcutaneous implantation also demonstrated that P(APM/MPC)-OCS-BP showed a weak inflammatory response due to the anti-inflammatory effect of OCS. Finally, in vivo and in vitro results revealed that P(APM/MPC)-OCS-BP exhibited an excellent anti-calcification property. In a word, this simple cooperative crosslinking strategy provides a novel solution to obtain BHVs with good mechanical properties, and HUVEC-cytocompatibility, anti-coagulation, anti-inflammatory and anti-calcification properties. It might be a promising alternative to GA-fixed BP and exhibited good prospects in clinical applications.

Mouse Melanoma Model in Tumor Vaccines and Immunotherapy Research.

Efficacy of novel cancer immunization protocols could be tested in cell line-derived xenograft tumor models (CDX), which are based on the implantation of human tumor cell lines into mice for the development of different tumors by numerous means, such as subcutaneous implantation and orthotopic, venial, or peritoneal injections. However, the disadvantages of this model are the biological alteration of the derived cells or the inability of the cell lines to accurately reflect the complexity of tumor heterogeneity. Therefore, syngeneic mouse models, which offer a relatively simple grafting technique, preservation of lineage hierarchy, and the ability to generate tumors in as little as 2-8weeks, are being used to study potential future applications in medical treatment, particularly immunotherapies. Here, we describe a B16.F10 C57Bl/6 mouse melanoma model we selected for therapeutic studies employing IL-2 and IL-12 immunization protocols. Procedure of tumor cells inoculation and melanoma development in mice is described in detail, as first and necessary set-up for successful immunization experiments.

A sustainable and self-healable silk fibroin nanocomposite with antibacterial and drug eluting properties for 3D printed wound dressings.

The development of self-healable and 3D printable hydrogels with decent biocompatibility, mechanical durability, adhesiveness to tissues, and antibacterial activity is of great importance for wound healing applications. In this study, we present a sustainable and environmentally friendly composite hydrogel consisting of silk fibroin (SF), oxidized salep (OS), and kappa carrageenan nanoparticles (NPs) for efficient wound care. The injectable nanocomposite hydrogel is highly stretchable and exhibits strong tissue adhesiveness and self-healing response through Schiff-base cross-linking between OS and SF. The tunable shear-thinning viscoelastic properties of the hydrogel facilitate 3D bioprinting with excellent shape adaptability (97.7 ± 1.1% recovery), enabling the fabrication of complex-shaped constructs. In vitro release kinetics of tetracycline (TC) encapsulated in kappa carrageenan NPs indicate a distinctive Korsmeyer-Peppas profile, including an initial burst release followed by a triphasic pattern controlled by the embedded NPs within the hydrogel matrix. The composite hydrogel shows a remarkable broad-spectrum antibacterial activity with substantial zones of inhibition against S. aureus (34.00 ± 1.00 mm) and E. coli (27.60 ± 2.08 mm) after 24 h of incubation at 37 °C. The addition of TC further enhances the zones of inhibition by approximately 45% for S. aureus and 27% for E. coli. The control group without kappa NP incorporation shows no zone of inhibition, underscoring the critical role of the nanoparticles in imparting antibacterial activity to the hydrogel. Cytocompatibility assays show the high viability of fibroblast (L929) cells (>90%) in vitro. In vivo biocompatibility studies through subcutaneous implantation also do not show malignancy, infection, abscess, necrosis, epidermal or dermal modifications, or inflammation of the wounds after 14 days post-injection. H&E staining shows that the biodegradation of the developed hydrogel facilitates the growth of non-inflammatory cells, leading to the substitution of the injected hydrogel with autologous tissue. The detailed analyses affirm that the multifunctional injectable hydrogel with self-healing and antibacterial properties has high potential for wound healing and skin tissue engineering.

A validated HPLC-MS/MS method for the quantification of systemic mifepristone after subcutaneous application in mice.

Mifepristone (RU486, MIF) is a synthetic steroidal hormone with progesterone and glucocorticoid receptor antagonistic characteristics. MIF is commonly used for pharmalogical abortions, but also for the treatment of endometrial and endocrine disorders. The goal of the study was to establish and validate a targeted HPLC-MS/MS method for the quantification of MIF and one of its active metabolites metapristone (MET) in plasma after subcutaneous implantation of slow-release MIF pellets in female BALB/c mice. Additionally, we aimed to apply the analytical method to tissue of several organs to understand the tissue-specific distribution of both analytes after release into systemic circulation. Sample preparation comprised a simple liquid-liquid extraction with diethylether and required 100 μl of plasma or homogenates of approximately 50 mg of tissue. The presented HPLC-MS/MS method showed high sensitivity with baseline separation of MIF, MET, and the internal standard levonorgestrel within a run time of only 8.0 minutes and comparable limits of quantification for plasma and tissue homogenates ranging from 40 pg ml-1 to 105 pg ml-1 for MIF and MET. The presented study is suitable for murine plasma and tissues and can be easily applied to human samples.

Time-dependent progress of lower urinary tract dysfunction in streptozotocin-induced diabetic rats with or without low-dose insulin treatment.

Objectives: To examine time-dependent functional and structural changes of the lower urinary tract in streptozotocin-induced diabetic rats with or without low-dose insulin treatment and explore the pathophysiological characteristics of insulin therapy on lower urinary tract dysfunction (LUTD) caused by diabetes mellitus (DM). Methods: Female Sprague-Dawley rats were divided into five groups: normal control (NC) group, 4 weeks insulin-treated DM (4-DI) group, 4 weeks DM (4-DM) group, 8 weeks insulin-treated DM (8-DI) group and 8 weeks DM (8-DM) group. DM was initially induced by i.p. injection of streptozotocin (65 mg/kg), and then the DI groups received subcutaneous implantation of insulin pellets under the mid dorsal skin. Voiding behavior was evaluated in metabolic cages. The function of bladder and urethra in vivo were evaluated by simultaneous recordings of the cystometrogram and urethral perfusion pressure (UPP) under urethane anesthesia. The function of bladder and urethra in vitro were tested by organ bath techniques. The morphologic changes of the bladder and urethra were investigated using Hematoxylin-Eosin and Masson's staining. Results: Both 4-and 8-weeks diabetic rats have altered micturition patterns, including increased 12-h urine volume, urinary frequency/12 hours and voided volume. In-vivo urodynamics showed the EUS bursting activity duration is longer in 4-DM group and shorter in 8-DM group compared to NC group. UPP change in 8-DM were significantly lower than NC group. While none of these changes were found between DI and NC groups. Organ bath showed the response to Carbachol and EFS in bladder smooth muscle per tissue weights was decreased significantly in 4- and 8-weeks DM groups compared with insulin-treated DM or NC groups. In contrast, the contraction of urethral muscle and maximum urethral muscle contraction per gram of the tissue to EFS stimulation were significantly increased in 4- and 8-weeks DM groups. The thickness of bladder smooth muscle was time-dependently increased, but the thickness of the urethral muscle had no difference. Conclusions: DM-induced LUTD is characterized by time-dependent functional and structural remodeling in the bladder and urethra, which shows the hypertrophy of the bladder smooth muscle, reduced urethral smooth muscle relaxation and EUS dysfunction. Low-dose insulin can protect against diuresis-induced bladder over-distention, preserve urethral relaxation and protect EUS bursting activity, which would be helpful to study the slow-onset, time-dependent progress of DM-induced LUTD.

Comparative subcutaneous and submuscular implantation of an electroencephalography device for long term electroencephalographic monitoring in dogs.

Implantable electroencephalography (EEG) recording devices have been used for ultra-long-term epilepsy monitoring both in clinical and home settings in people. Objective and accurate seizure detection and recording at home could be of great benefit in diagnosis, management and research in canine idiopathic epilepsy (IE). Continuous EEG monitoring would allow accurate detection of seizure patterns, seizure cycles, and seizure frequency. An EEG acquisition system usable in an "out of clinic" setting could improve owner and veterinary compliance for EEG diagnostics and seizure management. Whether a subcutaneous ultra-long term EEG monitoring device designed for humans could be implanted in dogs. Cadaver study with 8 medium to large breed dogs. Comparatively using a subcutaneous and submuscular approach to implant the UNEEG SubQ-Implant in each dog. Positioning was controlled via CT post implantation and cranial measurements were taken. In four of the eight dogs a submuscular implantation without any complications was possible. Complications were close contact to the optic nerve in the first approaches, before the implantation angle was changed and in the smallest dog contact of the implant with the orbital fat body. Cranial measurements of less than 95 mm length proved to be too small for reliable implantation via this approach. The subcutaneous approach showed severe limitations and the implant was prone to dislocation. The UNEEQ SubQ-Implant can be implanted in dogs, via submuscular approach. CT imaging and cranial measurements should be taken prior to implantation.

Dapansutrile OLT1177 suppresses foreign body response inflammation while preserving vascularisation of implanted materials.

Mitigating inflammation associated with the foreign body response (FBR) remains a significant challenge in enhancing the performance of implantable medical devices. Current anti-inflammatory approaches aim to suppress implant fibrosis, the major outcome of the FBR, but also inadvertently inhibit beneficial immune signalling necessary for tissue healing and vascularization. In a previous study, we demonstrated the feasibility of 'selective' immunosuppression targeting the NLRP3 inflammasome using the small molecule inhibitor MCC950, leading to reduced implant fibrosis without compromising healing and leading to enhanced vascularization. However, the clinical potential of MCC950 is severely limited due to its failure to pass Phase I clinical safety trials. This has triggered substantial efforts to develop safer analogues of NLRP3 inhibitors. Dapansutrile (OLT1177) is emerging as a leading candidate amongst current NLRP3 inhibitors, demonstrating both safety and effectiveness in a growing number of clinical indications and Phase 2 trials. While the anti-inflammatory effects of OLT1177 have been shown, validation of these effects in the context of implanted materials and the FBR have not yet been demonstrated. In this study, we show OLT1177 possesses beneficial effects on key cell types which drive FBR outcomes, including macrophages, fibroblasts, and smooth muscle cells. Evaluation of OLT1177 in a 28 day subcutaneous implantation model showed OLT1177 reduced fibrotic capsule formation while promoting implant vascularization. Mechanistic studies revealed that this occurred through activation of early pro-angiogenic markers while suppressing late-stage anti-angiogenic markers. These findings establish OLT1177 as a promising therapeutic approach for mitigating implant fibrosis while supporting vascularisation, suggesting a highly promising selective immunosuppressive strategy for the FBR warranting further research to explore its optimal integration into medical materials and devices.

Comparison study of surface-initiated hydrogel coatings with distinct side-chains for improving biocompatibility of polymeric heart valves.

Polymeric heart valves (PHVs) present a promising alternative for treating valvular heart diseases with satisfactory hydrodynamics and durability against structural degeneration. However, the cascaded coagulation, inflammatory responses, and calcification in the dynamic blood environment pose significant challenges to the surface design of current PHVs. In this study, we employed a surface-initiated polymerization method to modify polystyrene-block-isobutylene-block-styrene (SIBS) by creating three hydrogel coatings: poly(2-methacryloyloxy ethyl phosphorylcholine) (pMPC), poly(2-acrylamido-2-methylpropanesulfonic acid) (pAMPS), and poly(2-hydroxyethyl methacrylate) (pHEMA). These hydrogel coatings dramatically promoted SIBS's hydrophilicity and blood compatibility at the initial state. Notably, the pMPC and pAMPS coatings maintained a considerable platelet resistance performance after 12 h of sonication and 10 000 cycles of stretching and bending. However, the sonication process induced visible damage to the pHEMA coating and attenuated the anti-coagulation property. Furthermore, the in vivo subcutaneous implantation studies demonstrated that the amphiphilic pMPC coating showed superior anti-inflammatory and anti-calcification properties. Considering the remarkable stability and optimal biocompatibility, the amphiphilic pMPC coating constructed by surface-initiated polymerization holds promising potential for modifying PHVs.

In vitro chemical treatment of silk increases the expression of pro-inflammatory factors and facilitates degradation in rats.

Silk fiber is difficult to degrade in vivo, which limits its application in tissue engineering materials such as artificial nerves. Therefore, in this study aim to promote its degradation in vivo by chemical treating silk fibers in vitro. Sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), scanning electron microscopy (SEM) observations, mechanical test, Fourier transform infrared spectroscopy (FT-IR) measurements were used to investigate the degradation effect of chemicals (hydrochloric acid, phosphoric acid, acetic acid, sodium hydroxide, calcium hydroxide, sodium bicarbonate, and calcium chloride) on silk fiber in vitro. Immunofluorescence staining and transcriptome analysis were used to investigate the effect of inflammatory factors on the degradation of chemically treated silk fiber in rats. (1) Silks were separated into finer fibers in each group. (2) FT-IR absorption peaks of amides I, II, and III overlap in each group. (3) Silk degradation degree in each group was higher than that in an untreated group. The calcium chloride-treated group was completely degraded. (4) Fibronectin, collagen I, collagen III, integrin α and CD68 were immunofluorescence positive in all vegetation section. (5) There were no significant differences in the expressions of collagen I, collagen III, and fibronectin in the vegetations formed on the 14th day of subcutaneous implantation, while integrin α, CD68, TNF-α, IL-1b, and IL-23 express at higher levels with IL-10 at lower levels. All chemicals could completely degrade silk; however, their degradation products were not the same. The chemicals change the mechanical properties of silk by separating it into finer fibers, which increase the contact surface area between the silk and tissue fluid, accelerating the degradation of monofilaments in vivo by promoting inflammation and macrophage activity through the increased and decreased expressions of pro- and anti-inflammatory factors, respectively.

Delivery of Stem Cell-Rejuvenating Compounds via Subcutaneous Osmotic Pumps.

Aging is widely regarded as an irreversible physiological process throughout the mammalian lifespan, characterized by functional tissue deterioration and increased disease incidence. One hallmark of mammalian aging is reduced tissue regeneration, primarily attributed to the declining function of tissue-specific stem cells. In recent years, various strategies aimed at rejuvenating stem cells through drug-delivery systems have been extensively explored. Here we describe a method for the long-term, controlled, systemic delivery of drugs using subcutaneous implantations of osmotic pumps.

Structure and properties of the acellular porcine cornea irradiated with 60Co-γ and electron beam and its histocompatibility.

Acellular porcine cornea (APC) has been used in corneal transplantation and treatment of the corneal diseases. Sterilization is a key step before the application of graft, and irradiation is one of the most commonly used methods. In this paper, APC was prepared by the physical freeze-thawing combined with biological enzymes, and the effects of the electron beam (E-beam) and cobalt 60 (60Co-γ) at the dose of 15 kGy on the physicochemical properties, structure, immunogenicity, and biocompatibility of the APC were investigated. After decellularization, the residual DNA was 20.86 ± 1.02 ng/mg, and the α-Gal clearance rate was more than 99%. Irradiation, especially the 60Co-γ, reduced the cornea's transmittance, elastic modulus, enzymatic hydrolysis rate, swelling ratio, and cross-linking degree. Meanwhile, the diameter and spacing of the collagen fibers increased. In the rat subcutaneous implantation, many inflammatory cells appeared in the unirradiated APC, while the irradiated had good histocompatibility, but the degradation was faster. The lamellar keratoplasty in rabbits indicated that compared to the E-beam, the 60Co-γ damaged the chemical bond of collagen to a larger extent, reduced the content of GAGs, and prolonged the complete epithelization of the grafts. The corneal edema was more serious within 1 month after the surgery. After 2 months, the thickness of the APC with the two irradiation methods tended to be stable, but that in the 60Co-γ group became thinner. The pathological results showed that the collagen structure was looser and the pores were larger, indicating the 60Co-γ had a more extensive effect on the APC than the E-beam at 15 kGy.

Correlation between high- and low-voltage impedance measurements following subcutaneous implantable cardioverter-defibrillator implantation

Correlation between high- and low-voltage impedance measurements following subcutaneous implantable cardioverter-defibrillator implantation

Transforming layered 2D mats into multiphasic 3D nanofiber scaffolds with tailored gradient features for tissue regeneration.

Multiphasic scaffolds with tailored gradient features hold significant promise for tissue regeneration applications. Herein, this work reports the transformation of two-dimensional (2D) layered fiber mats into three dimensional (3D) multiphasic scaffolds using a 'solids-of-revolution' inspired gas-foaming expansion technology. These scaffolds feature precise control over fiber alignment, pore size, and regional structure. Manipulating nanofiber mat layers and Pluronic F127 concentrations allows further customization of pore size and fiber alignment within different scaffold regions. The cellular response to multiphasic scaffolds demonstrates the number of cells migrated and proliferated onto the scaffolds are mainly dependent on the pore size rather than fiber alignment. In vivo subcutaneous implantation of multiphasic scaffolds to rats reveals substantial cell infiltration, neo tissue formation, collagen deposition, and new vessel formation within scaffolds, greatly surpassing the capabilities of traditional nanofiber mats. Histological examination indicates the importance of optimizing pore size and fiber alignment for promotion of cell infiltration and tissue regeneration. Overall, these scaffolds have potential applications in tissue modeling, studying tissue-tissue interactions, interface tissue engineering, and high-throughput screening for optimized tissue regeneration.

Immediate implantation of ultrafine fiber slow-release system based on cell electrospinning to induce osteogenesis of mesenchymal stem cells.

This study presents the development and evaluation of a poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P34HB) ultrafine fiber slow-release system for in vivo osteogenic induction of human umbilical cord mesenchymal stem cells (HUCMSCs). Utilizing dual-nozzle and cell electrospinning techniques, the system encapsulates L-ascorbic acid-2-phosphate magnesium (ASP), β-glycerophosphate sodium and dexamethasone (DEX) within the fibers, ensuring sustained osteogenic differentiation. The scaffold's morphology, characterization, hydrophilicity, mechanical properties and cellular behavior were examined. Immediate subcutaneous implantation in rabbits was conducted to observe its ectopic osteogenic induction effect. Successfully fabricated P34HB ultrafine fiber slow-release system. Characterization confirmed the uniform distribution of HUCMSCs and inducing components within the scaffold, with no chemical reactions affecting the active components. In vitro tests showcased a prolonged release of DEX and ASP, while biocompatibility assays highlighted the scaffold's suitability for cellular growth. Alizarin Red, type I collagen, and osteopontin (OPN) staining verified the scaffold's potent osteogenic induction effect on HUCMSCs. Notably, immediate implantation into New Zealand White rabbits led to significant new bone formation within 8 weeks. These findings underscore the system's potential for immediate in vivo implantation without prior in vitro induction, marking a promising advancement in bone tissue engineering.

Protective effect of electroacupuncture at ST36 against damage of intestinal mucosa, oxidative stress and apoptosis induced by 5-FU chemotherapy in mice with colon cancer.

To observe the effect of electroacupuncture (EA) at "Zusanli"(ST36) on intestinal mucosal damage, intestinal mucosal oxidative stress injury and apoptosis induced by 5-fluorouraeil (5-FU) chemotherapy in colorectal cancer-bearing mice. Thirty male BALB/c mice were randomly divided into normal control, colorectal cancer (CT26), 5-FU, non-acupoint and ST36 groups, with 6 mice in each group. Except for those of the normal control group, mice of the remaining 4 groups received subcutaneous implantation of colorectal CT26 cell suspension (0.1 mL) in the right armpit for establishing colorectal cancer model. Rats of the 5-FU group, non-acupoint group and ST36 group were given with 5 mg/mL 5-FU solution once every 3 days for a total of 21 days. For mice of the non-acupoint group and ST36 group, EA (2 Hz, 1-2 mA) was applied to bilateral ST36 or non-acupoints (the bilateral sunken spots about 3 mm to the midpoint between the tail root and the anus) for 5 min after each intraperitoneal infusion of 5-FU, once every 3 days, for a total of 21 days. After the intervention, the diarrhea index was assessed. The length of colon (from the endpoint of cecum to the anal orifice) was measured. Histopathological changes of colonic mucosa were observed by H.E. staining, and the length of colonic villi was measured. The content of malondialdehyde (MDA), and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) of colonic tissue were detected by thibabituric acid, xanthine oxidase and colorimetric method, respectively. The rate of cell apoptosis in the colonic tissue was measured by TUNEL assay. The positive expressions of Bax and Bcl-2 in colonic tissue were determined by immunohistochemistry. The CT26 model group didn't show any significant changes in the diarrhea index, colon length, colon villus length, MDA content, SOD and GSH-Px activities, colonic cell apoptosis rate, and Bax and Bcl-2 expression levels when compared with the normal group. Compared with the CT26 group, the 5-FU group had a remarkable increase in the diarrhea index, MDA content, colonic cell apoptosis rate and Bax expression level (P<0.01, P<0.05), and a marked decrease in the colon length, colon villus length, SOD and GSH-Px activities and Bcl-2 expression level (P<0.01), suggesting the side effects of administration of 5-FU. Compared with the 5-FU group, the diarrhea index, MDA content, colonic cell apoptosis rate and Bax expression level were markedly decreased (P<0.05, P<0.01) and those of the colon length, colon villus length, SOD and GSH-Px activities and Bcl-2 expression level were obviously increased (P<0.01) in the ST36 group. Compared with the 5-FU group, the non-acupoint group also had an increase in the colon villus length, SOD and GSH-Px activities (P<0.01, P<0.05) and a decrease in the cell apoptosis rate (P<0.01). EA at ST36 has a positive effect in reducing intestinal mucosal damage induced by 5-FU chemotherapy in cancer-bearing mice, which may be related to its function in relieving oxidative stress injury and inhibiting apoptosis of colonic tissue.

ERECTILE DYSFUNCTION TREATMENT USING SUBCUTANEOUS IMPLANTS WITH A LONG-TERM EFFECT

Introduction. The article describes a new method of improving erectile function by incerting long-acting subcutaneous implants with the phosphodiesterase 5 (PDE 5) inhibitor.&#x0D; The aim of the study: To evaluate the effectiveness of tadalafil in the treatment of erectile dysfunction using bioidentical pellets.&#x0D; Materials and methods: The study included 10 men under 65 years of age who had suffered from erectile dysfunction for more than 1 year.&#x0D; For the examination before and 4 months after the intervention, the following were performed: filling out the MIEF-5 questionnaire, phical examination, Doppler of penile vessels, «Erection Hardness Scale», laboratory examination (general and biochemical blood tests, general urine analysis and hormonal testing, including determination of the levels of total testosterone, free testosterone, prolactin, estradiol and dehydroepiandrosterone sulfate.&#x0D; All patients received implants with bioidentical tadalafil 75 mg. The pellet was inserted in a sterile operating room through a 3 mm skin incision in the outer quadrant of the gluteal region and inserting the substance into the subcutaneous fat.&#x0D; Results: All patients showed an improvement in MIEF-5 from 14.7 ± 2.75 to 20.7 ± 1.49, an increase in systolic blood flow velocity and penile rigidity at the tenth minute after prostaglandin E1 injection on Doppler vascular examination.&#x0D; Conclusion: This study demonstrated the efficacy of tadalafil by pellet administration in the treatment of erectile dysfunction in men younger than 65 years.

Lysosome‐Inspired Enclosed and Deep Surface Decontamination Strategy for Management of Peri‐Implant Infections

AbstractSurface decontamination is a crucial step in the treatment of peri‐implant infections, yet deep and mild cleansing techniques are lacking. Drawing inspiration from lysosomes, which enclose hydrolytic enzymes within their membranes to safely and effectively degrade organics within cells, the use of a near‐infrared (NIR)/H2O2‐activated TiO2‐x‐Alginate system for enclosed and deep surface decontamination is proposed. It leverages synergistically generated reactive oxygen species (ROS) to eliminate bacterial contaminants, mimicking the process of lysosomal digestion. By employing Ca2+ spray‐induced surface gelation, the TiO2‐x and H2O2 around implant surface are enclosed, creating a membrane‐like isolation. This system robustly degrades extracellular polymeric substances (EPS)‐mimic biomacromolecules, removes organic residues (OR) from both mono‐species (Staphylococcus aureus and Porphyromonas gingivalis) biofilm and polymicrobial ex vivo biofilm of peri‐implantitis, while avoiding healthy tissue irritation. Encouragingly, this system has also demonstrated powerful decontamination capabilities when applied to clinic‐retrieved infected dental implants. Notably, this technique restores the pristine implant surface topography and chemical composition, which are further revealed by the minimal inflammation response observed in macrophage culture and subcutaneous implantation. Consequently, osteoblast functionalities are effectively restored, and re‐osseointegration in vivo is also greatly enhanced. Thus, this deep decontamination strategy holds great promise for clinical applications in managing peri‐implant infections.

Direct thrombin inhibitors fail to reverse the negative effects of heparin on lung growth and function after murine left pneumonectomy.

Neonates with congenital diaphragmatic hernia (CDH) frequently require cardiopulmonary bypass and systemic anticoagulation. We previously demonstrated that even subtherapeutic heparin impairs lung growth and function in a murine model of compensatory lung growth (CLG). The direct thrombin inhibitors (DTIs) bivalirudin and argatroban preserved growth in this model. Although DTIs are increasingly used for systemic anticoagulation clinically, patients with CDH may still receive heparin. In this experiment, lung endothelial cell proliferation was assessed following treatment with heparin-alone or mixed with increasing concentrations of bivalirudin or argatroban. The effects of subtherapeutic heparin with or without DTIs in the CLG model were also investigated. C57BL/6J mice underwent left pneumonectomy and subcutaneous implantation of osmotic pumps. Pumps were preloaded with normal saline, bivalirudin, or argatroban; treated animals received daily intraperitoneal low-dose heparin. In vitro, heparin-alone decreased endothelial cell proliferation and increased apoptosis. The effect of heparin on proliferation, but not apoptosis, was reversed by the addition of bivalirudin and argatroban. In vivo, low-dose heparin decreased lung volume compared with saline-treated controls. All three groups that received heparin demonstrated decreased lung function on pulmonary function testing and impaired exercise performance on treadmill tolerance testing. These findings correlated with decreases in alveolarization, vascularization, angiogenic signaling, and gene expression in the heparin-exposed groups. Together, these data suggest that bivalirudin and argatroban fail to reverse the inhibitory effects of subtherapeutic heparin on lung growth and function. Clinical studies on the impact of low-dose heparin with DTIs on CDH outcomes are warranted.NEW & NOTEWORTHY Infants with pulmonary hypoplasia frequently require cardiopulmonary bypass and systemic anticoagulation. We investigate the effects of simultaneous exposure to heparin and direct thrombin inhibitors (DTIs) on lung growth and pulmonary function in a murine model of compensatory lung growth (CGL). Our data suggest that DTIs fail to reverse the inhibitory effects of subtherapeutic heparin on lung growth and function. Clinical studies on the impact of heparin with DTIs on clinical outcomes are thus warranted.

CHONDROREGENERATIVE POTENTIAL ON SUBCUTANEOUS IMPLANTATION OF PLATELET-RICH FIBRIN (PRF)-IMPREGNATED DECELLULARIZED BOVINE CARTILAGE SCAFFOLD

The discovery of alternative implants with regenerative potential comparable to autologous cartilage continues to be encouraged because of the high donor site morbidity rate. This research tries to make an alternative implant that uses the concept of tissue engineering techniques in the form of endogenous regeneration by combining Decellularized Bovine Cartilage scaffold with Platelet-Rich Fibrin (BCPRF) which is implanted subcutaneously. The aim of this study was to compare the potential for chondroregeneration between BCPRF and autologous cartilage as assessed by chondrocyte cell formation, type 2 collagen thickness, and implant resorption rate in subcutaneous implantation. Using the research design method is a pretest-posttest control group design using New Zealand white rabbits. Forty eight experimental samples were divided into 2 groups which were treated with BCPRF and autologous cartilage implantation. Results were evaluated after 6 weeks. Evaluation was carried out on 39 samples. Microscopy showed better potential for autologous cartilage chondroregeneration than BCPRF with significant differences in the number of chondrocytes formed, the thickness of type 2 collagen (p=0.000), and the rate of implant resorption (p=0.000). In conclusion, the potential for chondroregeneration of autologous cartilage and BCPRF is significantly different in terms of the number of chondrocytes formed, the thickness of type 2 collagen, and the rate of implant resorption.