In the past few decades, 3D printing has played a significant role in fabricating scaffolds with consistent, complex structure that meet patient-specific needs in future clinical applications. Although many studies have contributed to this emerging field of additive manufacturing, which includes material development and computer-aided scaffold design, current quantitative analyses do not correlate material properties, printing parameters, and printing outcomes to a great extent. A model that correlates these properties has tremendous potential to standardize 3D printing for tissue engineering and biomaterial science. In this study, we printed poly(lactic-co-glycolic acid) (PLGA) utilizing a direct melt extrusion technique without additional ingredients. We investigated PLGA with various lactic acid: glycolic acid (LA:GA) molecular weight ratios and end caps to demonstrate the dependence of the extrusion process on the polymer composition. Micro-computed tomography was then used to evaluate printed scaffolds containing different LA:GA ratios, composed of different fiber patterns, and processed under different printing conditions. We built a statistical model to reveal the correlation and predominant factors that determine printing precision. Our model showed a strong linear relationship between the actual and predicted precision under different combinations of printing conditions and material compositions. This quantitative examination establishes a significant foreground to 3D print biomaterials following a systematic fabrication procedure. Additionally, our proposed statistical models can be applied to couple specific biomaterials and 3D printing applications for patient implants with particular requirements.

We describe the creation of polymeric microcapsules that can exhibit autonomous motion along defined trajectories. The capsules are made by cross-linking aqueous microdroplets of the biopolymer chitosan using glutaraldehyde. A coflow microfluidic tubing device is used to generate chitosan droplets containing nanoparticles (NPs) with an iron (Fe) core and a platinum (Pt) shell. The droplets are then incubated in a Petri dish with the cross-linking solution, and an external magnet is placed below the Petri dish to pull the NPs together as a collective "patch" on one end of each droplet. This results in cross-linked capsules (∼150 μm in diameter) with an anisotropic (patchy) structure. When these capsules are placed in a solution of H2O2, the Pt shell of the NPs catalyzes the decomposition of H2O2 into O2 gas, which is ejected from the patchy end in the form of bubbles. As a result, the capsules (which are termed micromotors) move in a direction opposite to the bubbles. Furthermore, the micromotors can be steered along specific paths by an external magnet (the magnetic response arises due to the Fe in the core of the NPs). A given micromotor can thus be directed to meet with and adhere to an inert capsule, i.e., a model cargo. Adhesion occurs due to the soft nature of the two structures. Once the cargo is picked up, the micromotor-cargo pair can be moved along a specific path to a destination, whereupon the cargo can be released from the micromotor. We believe these soft micromotors offer significant benefits over their existing hard counterparts because of their biocompatibility, biodegradability, and ability to encapsulate a variety of payloads.

Electroadhesion, i.e., adhesion induced by an electric field, occurs between non-sticky cationic and anionic hydrogels. Here, we demonstrate electroadhesion between cationic gels and animal (bovine) tissues. When gel and tissue are placed under an electric field (DC, 10 V) for 20 s, the pair strongly adhere, and the adhesion persists indefinitely thereafter. Applying the DC field with reversed polarity eliminates the adhesion. Electroadhesion works with the aorta, cornea, lung, and cartilage. We demonstrate the use of electroadhesion to seal cuts or tears in tissues or model anionic gels. Electroadhered gel-patches provide a robust seal over openings in bovine aorta, and a gel sleeve is able to rejoin pieces of a severed gel tube. These studies raise the possibility of using electroadhesion in surgery while obviating the need for sutures. Advantages include the ability to achieve adhesion on-command, and moreover the ability to reverse this adhesion in case of error.

We report the design of hydrogels that can act as "smart" valves or membranes. Each hydrogel is engineered with a pore (about 1 cm long and <1 mm thick) that remains closed under ambient conditions but opens under specific conditions. Our design is inspired by the stomatal valves in plant leaves, which regulate the movement of water and gases in and out of the leaves. The design features two different gels, active and passive, which are attached concentrically to form a disc-shaped hybrid film. The pore is created in the central active gel, and the conditions for opening the pore can be tuned based on the chemistry of this gel. For example, if the active gel is made from N-isopropylacrylamide (NIPA), the actuation of the pore depends on the temperature of water relative to 32 °C, which is the lower-critical solution temperature (LCST) of NIPA. The concentric design of our hybrid provides directionality to the volumetric transition of the active gel, i.e., it ensures that the pore opens as the active gel shrinks. In turn, contact with hot water (T > 32 °C) opens the pore and allows the water to pass through the gel. Conversely, the pore remains closed when the water is cold (T < 32 °C). The gel thereby acts as a "smart" valve that is able to regulate the flow of solvent depending on its properties. We have extended the concept to other stimuli that can cause gel-swelling transitions including solvent composition, pH, and light. Additionally, when two different gel-based valves are arranged in series, the assembly acts as a logical "AND" gate, i.e., water flows through the valve-combination only if it simultaneously satisfies two distinct conditions (such as its pH being below a critical value and its temperature being above a critical value).

External triggers such as pH or temperature can induce hydrogels to swell or shrink rapidly. Recently, these triggers have also been used to alter the three-dimensional (3-D) shapes of gels: for example, a flat gel sheet can be induced to fold into a tube. Self-folding gels are reminiscent of natural structures such as the Venus flytrap, which folds its leaves to entrap its prey. They are also of interest for applications in sensing or microrobotics. However, to advance the utility of self-folding gels, the range of triggers needs to be expanded beyond the conventional ones. Toward this end, we have designed a class of gels that change shape in response to very low concentrations of specific biomolecules. The gels are hybrids of three different constituents: (A) polyethylene glycol diacrylate (PEGDA); (B) gelatin methacrylate-co-polyethylene glycol dimethacrylate (GelMA-co-PEGDMA); and (C) N-isopropylacrylamide (NIPA). The thin-film hybrid is constructed as a bilayer or sandwich of two layers, with an A/B layer (alternating strips of A and B) sandwiched above a layer of gel C. Initially, when this hybrid gel is placed in water, the C layer is much more swollen than the A/B layer. Despite the swelling mismatch, the sheet remains flat because the A/B layer is very stiff. When collagenase enzyme is added to the water, it cleaves the gelatin chains in B, thus reducing the stiffness of the A/B layer. As a result, the swollen C layer is able to fold over the A/B layer, causing the sheet to transform into a specific shape. The typical transition is from flat sheet to closed hollow tube, and the time scale for this transition decreases with increasing enzyme concentration. Shape transitions are induced by enzyme levels as low as 0.75 U/mL. Interestingly, a shape transition is also induced by adding the lysate of murine fibroblast cells, which contains enzymes from the matrix metalloproteinase (MMP) family at levels around 0.1 U/mL (MMPs are similar to collagenase in their ability to cleave gelatin). We further show that transitions from flat sheets to other shapes such as helices and pancakes can be engineered by altering the design pattern of the gel. Additionally, we have made a rudimentary analog of the Venus flytrap, with two flat gels ("leaves") flanking a central folding gel ("hinge"). When enzyme is added, the hinge bends and brings the leaves together, trapping objects in the middle.