Scaffold-Mediated Drug Delivery for Enhanced Wound Healing: A Review.

Wound healing is a complex physiological process involving coordinated cellular and molecular events aimed at restoring tissue integrity. Acute wounds typically progress through the sequential phases of hemostasis, inflammation, proliferation, and remodeling, while chronic wounds, such as venous leg ulcers and diabetic foot ulcers, often exhibit prolonged inflammation and impaired healing. Traditional wound dressings, while widely used, have limitations such poor moisture retention and biocompatibility. To address these challenges and improve patient outcomes, scaffold-mediated delivery systems have emerged as innovative approaches. They offer advantages in creating a conducive environment for wound healing by facilitating controlled and localized drug delivery. The manuscript explores scaffold-mediated delivery systems for wound healing applications, detailing the use of natural and synthetic polymers in scaffold fabrication. Additionally, various fabrication techniques are discussed for their potential in creating scaffolds with controlled drug release kinetics. Through a synthesis of experimental findings and current literature, this manuscript elucidates the promising potential of scaffold-mediated drug delivery in improving therapeutic outcomes and advancing wound care practices.

Microglial over-pruning of synapses during development in autism-associated SCN2A-deficient mice and human cerebral organoids.

Autism spectrum disorder (ASD) is a major neurodevelopmental disorder affecting 1 in 36 children in the United States. While neurons have been the focus of understanding ASD, an altered neuro-immune response in the brain may be closely associated with ASD, and a neuro-immune interaction could play a role in the disease progression. As the resident immune cells of the brain, microglia regulate brain development and homeostasis via core functions including phagocytosis of synapses. While ASD has been traditionally considered a polygenic disorder, recent large-scale human genetic studies have identified SCN2A deficiency as a leading monogenic cause of ASD and intellectual disability. We generated a Scn2a-deficient mouse model, which displays major behavioral and neuronal phenotypes. However, the role of microglia in this disease model is unknown. Here, we reported that Scn2a-deficient mice have impaired learning and memory, accompanied by reduced synaptic transmission and lower spine density in neurons of the hippocampus. Microglia in Scn2a-deficient mice are partially activated, exerting excessive phagocytic pruning of post-synapses related to the complement C3 cascades during selective developmental stages. The ablation of microglia using PLX3397 partially restores synaptic transmission and spine density. To extend our findings from rodents to human cells, we established a microglia-incorporated human cerebral organoid model carrying an SCN2A protein-truncating mutation identified in children with ASD. We found that human microglia display increased elimination of post-synapse in cerebral organoids carrying the SCN2A mutation. Our study establishes a key role of microglia in multi-species autism-associated models of SCN2A deficiency from mouse to human cells.