Photobiomodulation and Vascularization in Conduit-Based Peripheral Nerve Repair: A Narrative Review.

Background: Peripheral nerve injuries pose a significant clinical issue for patients, especially in the most severe cases wherein complete transection (neurotmesis) results in total loss of sensory/motor function. Nerve guidance conduits (NGCs) are a common treatment option that protects and guides regenerating axons during recovery. However, treatment outcomes remain limited and often fail to achieve full reinnervation, especially in critically sized defects (>3 cm) where a lack of vascularization leads to neural necrosis. Conclusions: A multitreatment approach is, therefore, necessary to improve the efficacy of NGCs. Stimulating angiogenesis within NGCs can help alleviate oxygen deficiency through rapid inosculation with the host vasculature, whereas photobiomodulation therapy (PBMT) has demonstrated beneficial therapeutic effects on regenerating nerve cells and neovascularization. In this review, we discuss the current trends of NGCs, vascularization, and PBMT as treatments for peripheral nerve neurotmesis and highlight the need for a combinatorial approach to improve functional and clinical outcomes.

Prototype Development of a Temperature-Sensitive High-Adhesion Medical Tape to Reduce Medical-Adhesive-Related Skin Injury and Improve Quality of Care.

Medical adhesives are used to secure wound care dressings and other critical devices to the skin. Without means of safe removal, these stronger adhesives are difficult to painlessly remove from the skin and may cause medical-adhesive-related skin injuries (MARSI), including skin tears and an increased risk of infection. Lower-adhesion medical tapes may be applied to avoid MARSI, leading to device dislodgement and further medical complications. This paper outlines the development of a high-adhesion medical tape designed for low skin trauma upon release. By warming the skin-attached tape for 10-30 s, a significant loss in adhesion was achieved. A C14/C18 copolymer was developed and combined with a selected pressure-sensitive adhesive (PSA) material. The addition of 1% C14/C18 copolymer yielded the largest temperature-responsive drop in surface adhesion. The adhesive film was characterized using AFM, and distinct nanodomains were identified on the exterior surface of the PSA. Our optimized formulation yielded 67% drop in adhesion when warmed to 45 °C, perhaps due to melting nanodomains weakening the adhesive-substrate boundary layer. Pilot clinical testing resulted in a significant decrease in pain when a heat pack was used for removal, giving an average pain reduction of 66%.

Direct-Ink Write 3D Printing Multistimuli-Responsive Hydrogels and Post-Functionalization Via Disulfide Exchange.

Herein, we describe a multi-stimuli-responsive hydrogel that can be 3D printed via a direct-ink write process to afford cross-linked hydrogel networks that can be post-functionalized with thiol-bearing molecules. Poly(alkyl glycidyl ether)s with methacrylate groups at their termini were synthesized and self-assembled into hydrogels with three key stimuli-responsive behaviors necessary for extrusion based 3D printing: a sol-gel temperature response, shear-thinning behavior, and the ability to be photochemically crosslinked. In addition, the chemically crosslinked hydrogels demonstrated a temperature dependent swelling consistent with an LCST behavior. Pyridyl disulfide urethane methacrylate (PDS-UM) monomers were introduced into the network as a thiol-reactive handle for post-functionalization of the hydrogel. The reactivities of these hydrogels were investigated at different temperatures (5, 25, 37 °C) and swelling statuses (as-cured versus preswollen) using glutathione as a reactive probe. To illustrate the versatility of the platform, a number of additional thiol-containing probes such as proteins, polymers, and small molecules were conjugated to the hydrogel network at different temperatures, pH's, and concentrations. In a final demonstration of the multi-stimuli-responsive hydrogel platform, a customized DIW 3D printer was used to fabricate a printed object that was subsequently conjugated with a fluorescent tag and displayed the ability to change in size with environmental temperature.

Poly(alkyl glycidyl ether) hydrogels for harnessing the bioactivity of engineered microbes.

Herein, we describe a method to produce yeast-laden hydrogel inks for the direct-write 3D printing of cuboidal lattices for immobilized whole-cell catalysis. A poly(alkyl glycidyl ether)-based triblock copolymer was designed to have three important features for this application: (1) a temperature response, which allowed for facile processing of the material; (2) a shear response, which facilitated the extrusion of the material through a nozzle; and (3) UV light induced polymerization, which enabled the post-extrusion chemical crosslinking of network chains, and the fabrication of robust printed objects. These three key stimuli responses were confirmed via rheometrical characterization. A genetically-engineered yeast strain with an upregulated α-factor production pathway was incorporated into the hydrogel ink and 3D printed. The immobilized yeast cells exhibited adequate viability of 87.5% within the hydrogel. The production of the upregulated α-factor was detected using a detecting yeast strain and quantified at 268 nM (s = 34.6 nM) over 72 h. The reusability of these bioreactors was demonstrated via immersion of the yeast-laden hydrogel lattice in fresh SC media and confirmed by the detection of similar amounts of upregulated α-factor at 259 nM (s = 45.1 nM). These yeast-laden materials represent an attractive opportunity for whole-cell catalysis of other high-value products in a sustainable and continuous manner.