An investigation of water status in gelatin methacrylate hydrogels by means of water relaxometry and differential scanning calorimetry.

The relationship between molecular structure and water dynamics is a fundamental yet often neglected subject in the field of hydrogels for drug delivery, bioprinting, as well as biomaterial science and tissue engineering & regenerative medicine (TE&RM). Water is a fundamental constituent of hydrogel systems and engages via hydrogen bonding with the macromolecular network. The methods and techniques to measure and reveal the phenomena and dynamics of water within hydrogels are still limited. In this work, differential scanning calorimetry (DSC) was used as a quantitative method to analyze freezable (including free and freezable bound) and non-freezable bound water within gelatin methacrylate (GelMA) hydrogels. Nuclear magnetic resonance (NMR) is a complementary method for the study of water behavior and can be used to measure the spin-relaxation of water hydrogen nuclei, which is related to water dynamics. In this research, nuclear magnetic resonance relaxometry was employed to investigate the molecular state of water in GelMA hydrogels using spin-lattice (T1) and spin-spin (T2) spin-relaxation time constants. The data displays a trend of increasing bound water content with increasing GelMA concentration. In addition, T2 values were further applied to calculate microviscosity and translational diffusion coefficients. Water relaxation under various chemical environments, including different media, temperatures, gelatin sources, as well as crosslinking effects, were also examined. These comprehensive physical data sets offer fundamental insight into biomolecule transport within the GelMA hydrogel system, which ultimately are important for drug delivery, bioprinting, as well as biomaterial science and TE&RM communities.

Microporous/Macroporous Polycaprolactone Scaffolds for Dental Applications.

This study leverages the advantages of two fabrication techniques, namely, melt-extrusion-based 3D printing and porogen leaching, to develop multiphasic scaffolds with controllable properties essential for scaffold-guided dental tissue regeneration. Polycaprolactone-salt composites are 3D-printed and salt microparticles within the scaffold struts are leached out, revealing a network of microporosity. Extensive characterization confirms that multiscale scaffolds are highly tuneable in terms of their mechanical properties, degradation kinetics, and surface morphology. It can be seen that the surface roughness of the polycaprolactone scaffolds (9.41 ± 3.01 µm) increases with porogen leaching and the use of larger porogens lead to higher roughness values, reaching 28.75 ± 7.48 µm. Multiscale scaffolds exhibit improved attachment and proliferation of 3T3 fibroblast cells as well as extracellular matrix production, compared with their single-scale counterparts (an approximate 1.5- to 2-fold increase in cellular viability and metabolic activity), suggesting that these structures could potentially lead to improved tissue regeneration due to their favourable and reproducible surface morphology. Finally, various scaffolds designed as a drug delivery device were explored by loading them with the antibiotic drug cefazolin. These studies show that by using a multiphasic scaffold design, a sustained drug release profile can be achieved. The combined results strongly support the further development of these scaffolds for dental tissue regeneration applications.

Cross-linked poly(trimethylene carbonate-co-L-lactide) as a biodegradable, elastomeric scaffold for vascular engineering applications.

A series of copolymers of trimethylene carbonate (TMC) and L-lactide (LLA) were synthesized and evaluated as scaffolds for the production of artificial blood vessels. The polymers were end-functionalized with acrylate, cast into films, and cross-linked using UV light. The mechanical, degradation, and biocompatibility properties were evaluated. High TMC polymers showed mechanical properties comparable to human arteries (Young's moduli of 1.2-1.8 MPa and high elasticity with repeated cycling at 10% strain). Over 84 days degradation in PBS, the modulus and material strength decreased gradually. The polymers were nontoxic and showed good cell adhesion and proliferation over 7 days using human mesenchymal stem cells. When implanted into the rat peritoneal cavity, the polymers elicited formation of tissue capsules composed of myofibroblasts, resembling immature vascular smooth muscle cells. Thus, these polymers showed properties which were tunable and favorable for vascular tissue engineering, specifically, the growth of artificial blood vessels in vivo.

Electrospinning and crosslinking of low-molecular-weight poly(trimethylene carbonate-co-(L)-lactide) as an elastomeric scaffold for vascular engineering.

The growth of suitable tissue to replace natural blood vessels requires a degradable scaffold material that is processable into porous structures with appropriate mechanical and cell growth properties. This study investigates the fabrication of degradable, crosslinkable prepolymers of l-lactide-co-trimethylene carbonate into porous scaffolds by electrospinning. After crosslinking by γ-radiation, dimensionally stable scaffolds were obtained with up to 56% trimethylene carbonate incorporation. The fibrous mats showed Young's moduli closely matching human arteries (0.4-0.8MPa). Repeated cyclic extension yielded negligible change in mechanical properties, demonstrating the potential for use under dynamic physiological conditions. The scaffolds remained elastic and resilient at 30% strain after 84days of degradation in phosphate buffer, while the modulus and ultimate stress and strain progressively decreased. The electrospun mats are mechanically superior to solid films of the same materials. In vitro, human mesenchymal stem cells adhered to and readily proliferated on the three-dimensional fiber network, demonstrating that these polymers may find use in growing artificial blood vessels in vivo.