Dissolvable Immunomodulatory Microneedles for Treatment of Skin Wounds.

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.

Controlling cellular organization in bioprinting through designed 3D microcompartmentalization.

Controlling cellular organization is crucial in the biofabrication of tissue-engineered scaffolds, as it affects cell behavior as well as the functionality of mature tissue. Thus far, incorporation of physiochemical cues with cell-size resolution in three-dimensional (3D) scaffolds has proven to be a challenging strategy to direct the desired cellular organization. In this work, a rapid, simple, and cost-effective approach is developed for continuous printing of multicompartmental hydrogel fibers with intrinsic 3D microfilaments to control cellular orientation. A static mixer integrated into a coaxial microfluidic device is utilized to print alginate/gelatin-methacryloyl (GelMA) hydrogel fibers with patterned internal microtopographies. In the engineered microstructure, GelMA compartments provide a cell-favorable environment, while alginate compartments offer morphological and mechanical cues that direct the cellular orientation. It is demonstrated that the organization of the microtopographies, and consequently the cellular alignment, can be tailored by controlling flow parameters in the printing process. Despite the large diameter of the fibers, the precisely tuned internal microtopographies induce excellent cell spreading and alignment, which facilitate rapid cell proliferation and differentiation toward mature biofabricated constructs. This strategy can advance the engineering of functional tissues.

A simple, low cost and reusable microfluidic gradient strategy and its application in modeling cancer invasion.

Microfluidic chemical gradient generators enable precise spatiotemporal control of chemotactic signals to study cellular behavior with high resolution and reliability. However, time and cost consuming preparation steps for cell adhesion in microchannels as well as requirement of pumping facilities usually complicate the application of the microfluidic assays. Here, we introduce a simple strategy for preparation of a reusable and stand-alone microfluidic gradient generator to study cellular behavior. Polydimethylsiloxane (PDMS) is directly mounted on the commercial polystyrene-based cell culture surfaces by manipulating the PDMS curing time to optimize bonding strength. The stand-alone strategy not only offers pumpless application of this microfluidic device but also ensures minimal fluidic pressure and consequently a leakage-free system. Elimination of any surface treatment or coating significantly facilitates the preparation of the microfluidic assay and offers a detachable PDMS microchip which can be reused following to a simple cleaning and sterilization step. The chemotactic signal in our microchip is further characterized using numerical and experimental evaluations and it is demonstrated that the device can generate both linear and polynomial signals. Finally, the feasibility of the strategy in deciphering cellular behavior is demonstrated by exploring cancer cell migration and invasion in response to chemical stimuli. The introduced strategy can significantly decrease the complexity of the microfluidic chemotaxis assays and increase their throughput for various cellular and molecular studies.