Experimental animal modelling for pressure injury: A systematic review.

INTRODUCTION: Pressure injury (PI) is a potentially serious condition that is often a consequence of other medical illnesses. It remains a challenge for the clinicians and the researcher to fully understand and develop a technique for comprehending pathogenicity, prevention and treatment. Several animal models have been created to understand the multifaceted cellular and biochemical processes of PI. There are numerous known intrinsic and extrinsic factors influencing the recovery of PI. Some of the important factors are friction, spinal cord injury, diabetes, nutrition, aging, infection, medication, obesity and vascular diseases. The dearth of optimal, pre-clinical animal models capable of mimicking the human PI remains a major challenge for its cure. An ideal animal model must endeavour the reproducibility, clinical significance, and most importantly effective translation into clinical use. METHODS: In this current systematic review, a methodological literature review was conducted on the PRISMA guidelines. PubMed/Medline, Research Scholar and Science Direct databases were searched. We conferred the animal models like mice, rats, pigs and dogs used in the PI experiments between January 1980 to January 2021. Typically, methods like Ischemia-reperfusion (IR), monoplegia pressure sore and mechanical non-invasive have been discussed. These were used to generate pressure injuries in small and large animal models. RESULTS AND CONCLUSION: Different animal models (mouse, rat, pig, dog) were evaluated based on ease of handling, availability for research, their size, skin type and the technical skills required. Studies suggest that mice and rats are the best-suited animals as their skin healing by contraction resembles the skin healing in humans. In most of the studies with mice and rats, the time taken for the recovery was between 1 and 3 weeks. Further, various techniques discussed in the current systematics review, supports the statement that the Ischemia-reperfusion (IR) method is the most suited method to study pressure injury. It is a controlled method that can develop different stages of PI and does not require any specialized setup for the application.

The safety and efficacy of BCG encapsulated alginate particle (BEAP) against M.tb H37Rv infection in Macaca mulatta : A pilot study.

Due to the limited utility of Bacillus Calmette-Guérin (BCG), the only approved vaccine available for tuberculosis, there is a need to develop a more effective and safe vaccine. We evaluated the safety and efficacy of a dry powder aerosol (DPA) formulation of BCG encapsulated alginate particle (BEAP) and the conventional intradermal BCG immunization in infant rhesus macaques (Macaca mulatta). The infant macaques were immunized intratracheally with DPA of BEAP into the lungs. Animals were monitored for their growth, behaviour, any adverse and allergic response. The protective efficacy of BEAP was estimated by the ex-vivo H37Rv infection method. Post-immunization with BEAP, granulocytes count, weight gain, chest radiography, levels of liver secreted enzymes, cytokines associated with inflammation like TNF and IL-6 established that BEAP is non-toxic and it does not elicit an allergic response. The T cells isolated from BEAP immunized animals' blood, upon stimulation with M.tb antigen, secreted high levels of IFN-γ, TNF, IL-6 and IL-2. The activated T cells from BEAP group, when co-cultured with M.tb infected macrophages, eliminated largest number of infected macrophages compared to the BCG and control group. This study suggests the safety and efficacy of BEAP in Non-human primate model.

Aerosol immunization by alginate coated mycobacterium (BCG/MIP) particles provide enhanced immune response and protective efficacy than aerosol of plain mycobacterium against M.tb. H37Rv infection in mice.

BACKGROUND: With the aim of preparing a more effective, safe and economical vaccine for tuberculosis, inhalable live mycobacterium formulations were evaluated. METHODS: Alginate particles in the size range of 2-4 µm were prepared by encapsulating live Bacille Calmette-Guérin (BCG) and "Mycobacterium indicus pranii" (MIP). These particles were characterized for their size, stability and release profile. Mice were immunized with liquid aerosol or dry powder aerosol (DPA) alginate encapsulated mycobacterium particles and their in-vitro recall response and infection with mycobacterium H37Rv were investigated. RESULTS: It was found that the DPA of alginate encapsulated mycobacterium particles invoked superior immune response and provided higher protection in mice than the liquid aerosol. The BCG encapsulated in alginate particles (BEAP) and MIP encapsulated in alginate particles (MEAP) were engulfed by bone marrow dendritic cells (BMDCs) and co-localized with lysosome. The MEAP/BEAP activated BMDCs exhibited higher chemotaxis movement and had enhanced ability of antigen presentation to T cells. The in-vitro recall response of BEAP/MEAP immunized mice when compared in terms of proliferation index and Interferon gamma (IFN-gamma) released by splenocytes and mediastinal lymph node cells was found to be higher than mice immunized by liquid aerosol of BCG/MIP. Finally, different groups of immunized mice were infected with M. tb H37Rv and after 16 weeks the Colony forming units (CFUs) in lung and spleen estimated. The bacilli burden in the BEAP/MEAP immunized mice was significantly less than the respective liquid aerosol immunized mice and the histopathology of BEAP/MEAP immunized mice lungs showed very little damage. CONCLUSIONS: These inhale-able vaccines formulation of alginate coated live mycobacterium are more immunogenic as compared to the aerosol of bacilli and they provide better protection in mice when infected with H37Rv.