PEG-based hydrogels are used widely in exploratory tissue engineering applications but in general lack chemical and structural diversity. Additive manufacturing offers pathways to otherwise unattainable scaffold morphologies but has been applied sparingly to cross-linked hydrogels. Herein, mono methyl ether poly(ethylene glycol) (PEG) and PEG-diol were used to initiate the ring-opening copolymerization (ROCOP) of maleic anhydride and propylene oxide to yield well defined diblock and triblock copolymers of PEG-poly(propylene maleate) (PPM) and ultimately poly(propylene fumarate) (PPF) with different molecular mass PEG macroinitiators and block length ratios. Using continuous digital light processing (cDLP) hydrogels were photochemically printed from an aqueous solution which resulted in a 10-fold increase in elongation at break compared to traditional diethyl fumarate (DEF) based printing. Furthermore, PPF-PEG-PPF triblock hydrogels were also found to be biocompatible in vitro across a number of engineered MC3T3, NIH3T3, and primary Schwann cells.

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Hydrogels are used widely for exploratory tissue engineering studies. However, currently no hydrogel systems have been reported that exhibit a wide range of elastic modulus without changing precursor concentration, identity, or stoichiometry. Herein, ester and amide-based PEGoxime hydrogels with tunable moduli (~5-30 kPa) were synthesized with identical precursor mass fraction, stoichiometry, and concentration by varying the pH and buffer concentration of the gelation solution, exploiting the kinetics of oxime bond formation. The observed modulus range can be attributed to increasing amounts of network defects in slower forming gels, as confirmed by equilibrium swelling and small angle neutron scattering (SANS) experiments. Finally, hMSC viability was confirmed in these materials in a 24 h assay. While only an initial demonstration of the potential utility, the controlled variation in defect density and modulus is an important step forward in isolating system variables for hypothesis-driven biological investigations.

Peripheral nerve regeneration across large gaps remains clinically challenging and scaffold design plays a key role in nerve tissue engineering. One strategy to encourage regeneration has utilized nanofibers or conduits to exploit contact guidance within the neural regenerative milieu. Herein, we report the effect of nanofiber topography on two key aspects of regeneration: Schwann cell migration and neurite extension. Substrates possessing distinct diameter distributions (300 ± 40 to 900 ± 70 nm) of highly aligned poly­(ε-caprolactone) nanofibers were fabricated by touch-spinning. Cell migratory behavior and contact guidance were then evaluated both at the tissue level using dorsal root ganglion tissue explants and the cellular level using dissociated Schwann cells. Explant studies showed that Schwann cells emigrated significantly farther on fibers than control. However, both Schwann cells and neurites emigrated from the tissue explants directionally along the fibers regardless of their diameter, and the data were characterized by high variation. At the cellular level, dissociated Schwann cells demonstrated biased migration in the direction of fiber alignment and exhibited a significantly higher biased velocity (0.2790 ± 0.0959 μm·min–1) on 900 ± 70 nm fibers compared to other nanofiber groups and similar to the velocity found during explant emigration on 900 nm fibers. Therefore, aligned, nanofibrous scaffolds of larger diameters (900 ± 70 nm) may be promising materials to enhance various aspects of nerve regeneration via contact guidance alone. While cells track along with the fibers, this contact guidance is bidirectional along the fiber, moving in the plane of alignment. Therefore, the next critical step to direct regeneration is to uncover haptotactic cues that enhance directed migration.