Intranasal mRNA-LNP vaccination protects hamsters from SARS-CoV-2 infection.

Intranasal vaccination represents a promising approach for preventing disease caused by respiratory pathogens by eliciting a mucosal immune response in the respiratory tract that may act as an early barrier to infection and transmission. This study investigated immunogenicity and protective efficacy of intranasally administered messenger RNA (mRNA)-lipid nanoparticle (LNP) encapsulated vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Syrian golden hamsters. Intranasal mRNA-LNP vaccination systemically induced spike-specific binding [immunoglobulin G (IgG) and IgA] and neutralizing antibodies. Intranasally vaccinated hamsters also had decreased viral loads in the respiratory tract, reduced lung pathology, and prevented weight loss after SARS-CoV-2 challenge. Together, this study demonstrates successful immunogenicity and protection against respiratory viral infection by an intranasally administered mRNA-LNP vaccine.

Hyperosmolar potassium inhibits myofibroblast conversion and reduces scar tissue formation.

Scar formation is a natural result of almost all wound healing in adult mammals. Unfortunately, scarring disrupts normal tissue function and can cause significant physical and psychological distress. In addition to improving surgical techniques to limit scar formation, several therapies are under development towards the same goal. Many of these treatments aim to disrupt transforming growth factor ß1 (TGFß1) signaling, as this is a critical control point for fibroblast differentiation into myofibroblasts; a contractile cell that organizes synthesized collagen fibrils into scar tissue. The present study aimed to examine the role of hyperosmolar potassium gluconate (KGluc) on fibroblast function in skin repair. KGluc was first determined to negatively regulate fibroblast proliferation, metabolism, and migration in a dose-dependent manner in vitro. Increasing concentrations of KGluc also inhibited differentiation into myofibroblasts, suggesting that local KGluc treatment might reduce fibrosis. KGluc delivery was confirmed via loading into collagen hydrogels and used to treat a full thickness skin wound in mice. KGluc qualitatively slowed initial closure of the wounds and resulted in tissue that more closely resembled mature, healthy skin (epidermal thickness and dermal-epidermal morphology) when compared to unloaded collagen hydrogels. KGluc treatment significantly reduced the number of myofibroblasts within the dermis while upregulated blood vessel density with respect to unloaded hydrogels, likely a result of disruption of TGFß1 signaling. Taken together, these data demonstrate the effectiveness of KGluc treatment on skin wound healing and suggest that this may be an efficient treatment to limit scar formation.

A Tunable Silk Hydrogel Device for Studying Limb Regeneration in Adult Xenopus Laevis.

In certain amphibian models limb regeneration can be promoted or inhibited by the local wound bed environment. This research introduces a device that can be utilized as an experimental tool to characterize the conditions that promotes limb regeneration in the adult frog (Xenopus laevis) model. In particular, this device was designed to manipulate the local wound environment via a hydrogel insert. Initial characterization of the hydrogel insert revealed that this interaction had a significant influence on mechanical forces to the animal, due to the contraction of the hydrogel. The material and mechanical properties of the hydrogel insert were a factor in the device design in relation to the comfort of the animal and the ability to effectively manipulate the amputation site. The tunable features of the hydrogel were important in determining the pro-regenerative effects in limb regeneration, which was measured by cartilage spike formation and quantified by micro-computed tomography. The hydrogel insert was a factor in the observed morphological outcomes following amputation. Future work will focus on characterizing and optimizing the device's observed capability to manipulate biological pathways that are essential for limb regeneration. However, the present work provides a framework for the role of a hydrogel in the device and a path forward for more systematic studies.

Bio-functionalized silk hydrogel microfluidic systems.

Bio-functionalized microfluidic systems were developed based on a silk protein hydrogel elastomeric materials. A facile multilayer fabrication method using gelatin sacrificial molding and layer-by-layer assembly was implemented to construct interconnected, three dimensional (3D) microchannel networks in silk hydrogels at 100 µm minimum feature resolution. Mechanically activated valves were implemented to demonstrate pneumatic control of microflow. The silk hydrogel microfluidics exhibit controllable mechanical properties, long-term stability in various environmental conditions, tunable in vitro and in vivo degradability in addition to optical transparency, providing unique features for cell/tissue-related applications than conventional polydimethylsiloxane (PDMS) and existing hydrogel-based microfluidic options. As demonstrated in the work here, the all aqueous-based fabrication process at ambient conditions enabled the incorporation of active biological substances in the bulk phase of these new silk microfluidic systems during device fabrication, including enzymes and living cells, which are able to interact with the fluid flow in the microchannels. These silk hydrogel-based microfluidic systems offer new opportunities in engineering active diagnostic devices, tissues and organs that could be integrated in vivo, and for on-chip cell sensing systems.

Evaluation of a population-based program of expedited partner therapy for gonorrhea and chlamydial infection.

OBJECTIVE: To evaluate a partner notification program for gonorrhea and chlamydial infection that involves communitywide access to free patient-delivered partner therapy (PDPT) and use of case-report forms to triage patients to receive partner notification assistance. METHODS: We evaluated program components in randomly selected cases and compared outcomes before and after program institution. RESULTS: Following institution of the program, the percentage of cases who received PDPT from their diagnosing clinician increased from 5.6% to 16% (adjusted OR 3.2, 2.5-4.1). Among randomly selected cases, those referred to the health department via the case-report form were significantly more likely than nonreferred cases to have untreated sex partners (76% vs. 35%, OR 6.0, 95% CI 4.5-8.0), to accept PDPT from the health department (36% vs. 14%, 3.3, 95% CI 2.4-4.7), and to request that health department staff notify a partner for them (11% vs. 3%, OR 3.5, 95% CI 1.8-6.7). The percentage of cases classified as having all of their partners treated increased from 39% to 65% concurrent with institution of the program. CONCLUSIONS: A public health program that promotes routine use of PDPT and referral of selected patients for partner notification assistance appears to have improved partner notification outcomes.