ABSTRACT
Sustained inflammation can halt or delay wound healing, and macrophages play a central role in wound healing. Inflammatory macrophages are responsible for the removal of pathogens, debris, and neutrophils, while anti-inflammatory macrophages stimulate various regenerative processes. Recombinant human Proteoglycan 4 (rhPRG4) is shown to modulate macrophage polarization and to prevent fibrosis and scarring in ear wound healing. Here, dissolvable microneedle arrays (MNAs) carrying rhPRG4 are engineered for the treatment of skin wounds. The in vitro experiments suggest that rhPRG4 modulates the inflammatory function of bone marrow-derived macrophages. Degradable and detachable microneedles are developed from gelatin methacryloyl (GelMA) attach to a dissolvable gelatin backing. The developed MNAs are able to deliver a high dose of rhPRG4 through the dissolution of the gelatin backing post-injury, while the GelMA microneedles sustain rhPRG4 bioavailability over the course of treatment. In vivo results in a murine model of full-thickness wounds with impaired healing confirm a decrease in inflammatory biomarkers such as TNF-α and IL-6, and an increase in angiogenesis and collagen deposition. Collectively, these results demonstrate rhPRG4-incorporating MNA is a promising platform in skin wound healing applications.
Subject(s)
Gelatin , Needles , Skin , Wound Healing , Animals , Wound Healing/drug effects , Humans , Skin/injuries , Skin/drug effects , Mice , Gelatin/chemistry , Macrophages/drug effects , Macrophages/metabolism , Macrophages/immunology , Proteoglycans/chemistry , Proteoglycans/pharmacology , Mice, Inbred C57BL , Recombinant Proteins/administration & dosage , Recombinant Proteins/pharmacology , MethacrylatesABSTRACT
Cellular agriculture is an emerging field rooted in engineering meat-mimicking cell-laden structures using tissue engineering practices that have been developed for biomedical applications, including regenerative medicine. Research and industrial efforts are focused on reducing the cost and improving the throughput of cultivated meat (CM) production using these conventional practices. Due to key differences in the goals of muscle tissue engineering for biomedical versus food applications, conventional strategies may not be economically and technologically viable or socially acceptable. In this review, these two fields are critically compared, and the limitations of biomedical tissue engineering practices in achieving the important requirements of food production are discussed. Additionally, the possible solutions and the most promising biomanufacturing strategies for cellular agriculture are highlighted.
Subject(s)
Biomedical Engineering , Tissue Engineering , Regenerative Medicine , MusclesABSTRACT
Background: Combination antiretroviral therapy has significantly advanced HIV-1 infection treatment. However, HIV-1 remains persistent in the brain; the inaccessibility of the blood-brain barrier allows for persistent HIV-1 infections and neuroinflammation. Nanotechnology-based drug carriers such as nanodiscoidal bicelles can provide a solution to combat this challenge. Methods: This study investigated the safety and extended release of a combination antiretroviral therapy drug (tenofovir)-loaded nanodiscs for HIV-1 treatment in the brain both in vitro and in vivo. Result: The nanodiscs entrapped the drug in their interior hydrophobic core and released the payload at the desired location and in a controlled release pattern. The study also included a comparative pharmacokinetic analysis of nanodisc formulations in in vitro and in vivo models. Conclusion: The study provides potential applications of nanodiscs for HIV-1 therapy development.
