Dynamic, multimodal hydrogel actuators using porphyrin-based visible light photoredox catalysis in a thermoresponsive polymer network.

Hydrogels that can respond to multiple external stimuli represent the next generation of advanced functional biomaterials. Here, a series of multimodal hydrogels were synthesized that can contract and expand reversibly over several cycles while changing their mechanical properties in response to blue and red light, as well as heat (∼50 °C). The light-responsive behavior was achieved through a photoredox-based mechanism consisting of photoinduced electron transfer from a zinc porphyrin photocatalyst in its excited state to oligoviologen-based macrocrosslinkers, both of which were integrated into the hydrogel polymer network during gel formation. Orthogonal thermoresponsive properties were also realized by introducing N-isopropyl acrylamide (NIPAM) monomer simultaneously with hydroxyethyl acrylate (HEA) in the pre-gel mixture to produce a statistical 60 : 40 HEA : NIPAM polymer network. The resultant hydrogel actuators - crosslinked with either a styrenated viologen dimer (2V4+-St) or hexamer (6V12+-St) - were exposed to red or blue light, or heat, for up to 5 h, and their rate of contraction, as well as the corresponding changes in their physical properties (i.e., stiffness, tensile strength, Young's modulus, etc.), were measured. The combined application of blue light and heat to the 6V12+-St-based hydrogels was also demonstrated, resulting in hydrogels with more than two-fold faster contraction kinetics and dramatically enhanced mechanical robustness when fully contracted. We envision that the reported materials and the corresponding methods of remotely manipulating the dynamic hydrogels may serve as a useful blueprint for future adaptive materials used in biomedical applications.

Manipulating Air-Gap Electrospinning to Create Aligned Polymer Nanofiber-Wrapped Glass Microfibers for Cortical Bone Tissue Engineering.

Osteons are the repeating unit throughout cortical bone, consisting of canals filled with blood and nerve vessels surrounded by concentric lamella of hydroxyapatite-containing collagen fibers, providing mechanical strength. Creating a biodegradable scaffold that mimics the osteon structure is crucial for optimizing cellular infiltration and ultimately the replacement of the scaffold with native cortical bone. In this study, a modified air-gap electrospinning setup was exploited to continuously wrap highly aligned polycaprolactone polymer nanofibers around individual 1393 bioactive glass microfibers, resulting in a synthetic structure similar to osteons. By varying the parameters of the device, scaffolds with polymer fibers wrapped at angles between 5-20° to the glass fiber were chosen. The scaffold indicated increased cell migration by demonstrating unidirectional cell orientation along the fibers, similar to recent work regarding aligned nerve and muscle regeneration. The wrapping decreased the porosity from 90% to 80%, which was sufficient for glass conversion through ion exchange validated by inductively coupled plasma. Scaffold degradation was not cytotoxic. Encapsulating the glass with polymer nanofibers caused viscoelastic deformation during three-point bending, preventing typical brittle glass fracture, while maintaining cell migration. This scaffold design structurally mimics the osteon, with the intent to replace its material compositions for better regeneration.

Bio-conjugation of platelet-rich plasma and alginate through carbodiimide chemistry for injectable hydrogel therapies.

Alginate is a highly tailorable, biocompatible polymer whose properties can be tuned to mimic the properties of native nucleus pulposus (NP) tissue. Platelet-rich plasma (PRP) is a highly accessible, inexpensive, and readily available mix of pro-regenerative factors. By functionalizing alginate with PRP, a mechanically optimized, bioactive alginate NP analogue may stimulate NP cells to proliferate and accumulate matrix over a longer period of time than if the PRP were solely encapsulated within the hydrogel. In this study, PRP was chemically bound to alginate using carbodiimide chemistry and mechanically, physically, and cytologically compared to plain alginate as well as alginate containing free-floating lyophilized PRP. The alginates were mechanically and physically characterized; PRP-conjugated alginate had similar mechanical properties to controls and had the benefit of retained PRP proteins within the hydrogel. Human nucleus pulposus cells (hNPCs) were seeded within the modified alginates and cultured for 14 days. Quantification data of glycosaminoglycans suggests that PRP-incorporated alginate has the potential to increase ECM production within the characterized alginate constructs, and that PRP-functionalized alginate can retain protein within the hydrogel over time. This is the first study to functionalize the milieu of PRP proteins onto alginate and characterize the mechanical and physical properties of the modified alginates. This study also incorporates hNPCs into the characterized PRP-modified alginates to observe phenotypic maintenance when encapsulated within the in situ gelling constructs.

A Critical Review and Perspective of Honey in Tissue Engineering and Clinical Wound Healing.

Significance: Historically, honey has been regarded as a potent agent in bacterial inhibition and wound healing. An increased prevalence of antibiotic resistant pathogens spurred an initial resurgence in honey's clinical popularity, with it quickly finding a place in wound care and regenerative medicine. However, this renewed usage demanded a need for improved delivery and overall research of its bioactive properties. This review provides an overview of the antibacterial properties and clinical use of honey. Recent Advances: The past and present clinical use of honey is noted, focusing specifically on burns and ulcers, as these are the most common applications of the natural agent. While honey is often used without modification clinically, there are also commercially available products ranging from dressings to gels, which are discussed. Critical Issues: Despite these products growing in popularity, the need for improved delivery and a structure to support wound healing could improve the treatment method. Future Directions: Tissue engineering scaffolds can provide an alternative method of honey delivery with research focusing primarily on electrospun scaffolds, hydrogels, and cryogels. Current studies on these scaffolds are discussed with respect to their advantages and potential for future clinical work. Overall, this review provides a comprehensive overview of the properties of honey, its current use in wound healing, and the potential for future incorporation into tissue-engineered scaffolds to provide an innovative wound healing agent.

Reversible Hydrogel Photopatterning: Spatial and Temporal Control over Gel Mechanical Properties Using Visible Light Photoredox Catalysis.

There is a growing interest in being able to control the mechanical properties of hydrogels for applications in materials, medicine, and biology. Primarily, changes in the hydrogel's physical properties, i.e., stiffness, toughness, etc., are achieved by modulating the network cross-linking chemistry. Common cross-linking strategies rely on (i) irreversible network bond degradation and reformation in response to an external stimulus, (ii) using dynamic covalent chemistry, or (iii) isomerization of integrated functional groups (e.g., azobenzene or spiropyran). Many of these strategies are executed using ultraviolet or visible light since the incident photons serve as an external stimulus that affords spatial and temporal control over the mechanical adaptation process. Here, we describe a different type of hydrogel cross-linking strategy that uses a redox-responsive cross-linker, incorporated in poly(hydroxyethyl acrylate)-based hydrogels at three different weight percent loadings, which consists of two viologen subunits tethered by hexaethylene glycol and capped with styrene groups at each terminus. These dicationic viologen subunits (V2+) can be reduced to their monoradical cations (V•+) through a photoinduced electron transfer (PET) process using a visible light-absorbing photocatalyst (tris(bipyridine)ruthenium(II) dichloride) embedded in the hydrogel, resulting in the intramolecular stacking of viologen radical cations, through radical-radical pairing interactions, while losing two positive charges and the corresponding counteranions from the hydrogel. It is shown how this concerted process ultimately leads to collapse of the hydrogel network and significantly (p < 0.05) increases (by nearly a factor of 2) the soft material's stiffness, tensile strength, and percent elongation at break, all of which is easily reversed via oxidation of the viologen subunits and swelling in water. Application of this reversible PET process was demonstrated by photopatterning the same hydrogel multiple times, where the pattern was "erased" each time by turning off the blue light (∼450 nm) source and allowing for oxidation and reswelling in between patterning steps. The areas of the hydrogel that were masked exhibited lower (by 1-2 kPa) shear storage moduli (G') than the areas that were irradiated for 1.5 h. Moreover, because the viologen subunits in the functional cross-linker are electrochromic, it is possible to visualize the regions of the hydrogel that undergo changes in mechanical properties. This visualization process was illustrated by photopatterning a larger hydrogel (∼9.5 cm on its longest side) with a photomask in the design of an array of stars.