The effect of medicinal electroapplication of the biologically active agent "Pelamine" from the ELAV-8 device on microcirculation in the rabbit ear

The study was the first to study the effect of pulsed electric currents from the ELAV–8 device and the biologically active substance "Pelamine" on microcirculation in the rabbit ear. It was found that pulsed currents from the ELAV-8 device with a frequency of 100 Hz, as well as the biologically active agent "Pelamine" injected into the rabbit's paravertebral region by means of pulsed currents, have a vasodilatory effect on the vascular bed of the rabbit's ear. At the same time, transdermal administration of the biologically active agent "Pelamine" with the help of currents from the ELAV-8 device has a more prolonged effect on vasodilation. Key words: Microcirculation, rabbit ear, paravertebral region, vascular diameter, "Pelamine", ELAV-8 device.

Sequential Enzymatic Digestion of Different Cartilage Tissues: A Rapid and High-Efficiency Protocol for Chondrocyte Isolation, and Its Application in Cartilage Tissue Engineering

Objective The classic chondrocyte isolation protocol is a 1-step enzymatic digestion protocol in which cartilage samples are digested in collagenase solution for a single, long period. However, this method usually results in incomplete cartilage dissociation and low chondrocyte quality. In this study, we aimed to develop a rapid, high-efficiency, and flexible chondrocyte isolation protocol for cartilage tissue engineering. Design Cartilage tissues harvested from rabbit ear, rib, septum, and articulation were minced and subjected to enzymatic digestion using the classic protocol or the newly developed sequential protocol. In the classic protocol, cartilage fragments were subjected to one 12-hour digestion. In the sequential protocol, cartilage fragments were sequentially subjected to 2-hour first digestion, followed by two 3-hour digestions. The collected cells were then subjected to analyses of cell-yield efficiency, viability, proliferation, phenotype, and cartilage matrix synthesis capacity Results Overall, the sequential protocol exhibited higher cell-yield efficiency than the classic protocol for the 4 cartilage types. The cells harvested from the second and third digestions demonstrated higher cell viability, more proliferative activity, a better chondrocyte phenotype, and a higher cartilage-specific matrix synthesis ability than those harvested from the first digestion and after the classic 1-step protocol. Conclusions The sequential protocol is a rapid, flexible, high-efficiency chondrocyte isolation protocol for different cartilage tissues. We recommend using this protocol for chondrocyte isolation, and in particular, the cells obtained after the subsequent 3-hour sequential digestions should be used for chondrocyte-based therapy.

A Four-Step Cascade Drug-Release Management Strategy for Transcatheter Arterial Chemoembolization (TACE) Therapeutic Applications

The purpose of this study was to develop a four-step cascade drug-release system for transcatheter arterial chemoembolization (TACE) therapeutic applications according to disease-driven and patient-focused design theories. The four steps underlying these strategies involve the blockage of nutrient supply, nanoparticles, codelivery and the cell cytotoxic effect. Calibrated spherical gellan gum (GG) and nanoparticle-containing gellan gum microspheres were prepared using a water-in-oil emulsification method. Self-assembled nanoparticles featuring amine-functionalized graphene oxide (AFGO) as the doxorubicin (Dox) carrier were prepared. The results confirm that, as a drug carrier, AFGO–Dox nanoparticles can facilitate the transport of doxorubicin into HepG2 liver cancer cells. Subsequently, AFGO–Dox was introduced into gellan gum (GG) microspheres, thus forming GG/AFGO–Dox microspheres with a mean size of 200–700 μm. After a drug release experiment lasting 28 days, the amount of doxorubicin released from 674 and 226 μm GG/AFGO–Dox microspheres was 2.31 and 1.18 μg/mg, respectively. GG/AFGO–Dox microspheres were applied in a rabbit ear embolization model, where ischemic necrosis was visible on the ear after 12 days. Our aim for the future is to provide better embolization agents for transcatheter arterial chemoembolization (TACE) using this device.

The effects of kiwifruit dressing on hypertrophic scars in a rabbit ear model

Aims: Hypertrophic scars show abnormal responses during healing. These scars, associated with dysregulated growth and excessive collagen formation, can have both functional and cosmetic consequences for patients. The present study evaluated the effects of kiwifruit on hypertrophic scars in a rabbit ear model. Methods: This study included 13 New Zealand albino rabbits with full thickness wounds down to the cartilage (four wounds per ear; total: 104 scars). Sixteen days after initial wound formation, one ear of each rabbit was treated with daily kiwifruit dressing, while the other ear (control group) was dressed after normal saline irrigation for 10 days. Harvested skin samples were examined for histopathological, morphometric and immunohistochemical results. Results: In comparison with the control group, early kiwifruit dressing significantly reduced the scar elevation index, fibroblast count and dermal collagen organisation. The ratio of collagen type III to total collagen immunoreactivity, inflammation and dermal capillary count increased significantly in the treated group, compared to the untreated controls. Conclusion: Based on the findings, early kiwifruit dressing improved the histological features of cutaneous wounds in rabbits. Therefore, this approach may be effective in clinical practice.

The Acne-treatment Potential of Cinnamomum Camphora Chvar. Borneol Essential Oil in Vitro and in Vivo

Background: Acne is one of the most common chronic inflammatory skin diseases, abnormal proliferation of keratinocytes can block the hair follicle sebaceous glands result in the formation of acne. Most drugs to treat acne can cause a variety of side effects, therefore, it is important to seek natural and safe complementary and alternative therapies.Methods: The inhibitory effects of BEO were determined on the proliferation of human keratinocyte (HaCaT) cells induced by heat-inactivated Staphylococcus epidermidis and release of the inflammatory mediators. Further, a component-target-signal pathway for BEO’s effects on acne was constructed through network pharmacology and the mechanism of BEO action was studied in vivo through the rabbit ear acne model.Results: BEO inhibited both cell proliferation, induced by heat-inactivated Staphylococcus epidermidis (p < 0.0001), and release of the inflammatory mediators TNF-α (p < 0.0001) and IL-1β (p < 0.05) in a dose-dependent manner (r = -0.9952, -0.9492), in a HaCaT cell-model of acne. A network pharmacology analysis of the chemical components of BEO characterized these effects as multi-component, multi-target and multi-pathway. All targets were mainly associated with metabolic pathways, the toll-like receptor signaling pathway and the NF-κB signaling pathway. BEO also reduced the severity of acne lesions, induced by intracutaneous injection of S. epidermidis in a rabbit ear acne model. The expression of inflammatory mediators and key signaling pathway components, including TLR2, AKT, P13K, NF-κB, TNF-α, IL-1β in rabbit ear, and TNF-α and IL-1 β in serum, were down-regulated (p < 0.05), indicating that BEO acts by inhibiting the pro-inflammatory TLR2/PI3K-AKT/NF-κB signaling pathway.Conclusion: The current results showed that BEO has clear potential for development into a natural and safe anti-inflammatory skin preparation, which is an effective alternative to conventional treatments containing antibiotics and synthetic anti-inflammatory agents.

Local Delivery of Pirfenidone by PLA Implants Modifies Foreign Body Reaction and Prevents Fibrosis

Peri-implant fibrosis (PIF) increases the postsurgical risks after implantation and limits the efficacy of the implantable drug delivery systems (IDDS). Pirfenidone (PF) is an oral anti-fibrotic drug with a short (<3 h) circulation half-life and strong adverse side effects. In the current study, disk-shaped IDDS prototype combining polylactic acid (PLA) and PF, PLA@PF, with prolonged (~3 days) PF release (in vitro) was prepared. The effects of the PLA@PF implants on PIF were examined in the rabbit ear skin pocket model on postoperative days (POD) 30 and 60. Matching blank PLA implants (PLA0) and PLA0 with an equivalent single-dose PF injection performed on POD0 (PLA0+injPF) served as control. On POD30, the intergroup differences were observed in α-SMA, iNOS and arginase-1 expressions in PLA@PF and PLA0+injPF groups vs. PLA0. On POD60, PIF was significantly reduced in PLA@PF group. The peri-implant tissue thickness decreased (532 ± 98 µm vs. >1100 µm in control groups) approaching the intact derma thickness value (302 ± 15 µm). In PLA@PF group, the implant biodegradation developed faster, while arginase-1 expression was suppressed in comparison with other groups. This study proves the feasibility of the local control of fibrotic response on implants via modulation of foreign body reaction with slowly biodegradable PF-loaded IDDS.