3D Printed Programmable Release Capsules

Abstract

The development of methods for achieving precise spatiotemporal control over chemical and biomolecular gradients could enable significant advances in areas such as synthetic tissue engineering, biotic–abiotic interfaces, and bionanotechnology. Living organisms guide tissue development through highly orchestrated gradients of biomolecules that direct cell growth, migration, and differentiation. While numerous methods have been developed to manipulate and implement biomolecular gradients, integrating gradients into multiplexed, three-dimensional (3D) matrices remains a critical challenge. Here we present a method to 3D print stimuli-responsive core/shell capsules for programmable release of multiplexed gradients within hydrogel matrices. These capsules are composed of an aqueous core, which can be formulated to maintain the activity of payload biomolecules, and a poly(lactic-co-glycolic) acid (PLGA, an FDA approved polymer) shell. Importantly, the shell can be loaded with plasmonic gold nanorods (AuNRs), which permits selective rupturing of the capsule when irradiated with a laser wavelength specifically determined by the lengths of the nanorods. This precise control over space, time, and selectivity allows for the ability to pattern 2D and 3D multiplexed arrays of enzyme-loaded capsules along with tunable laser-triggered rupture and release of active enzymes into a hydrogel ambient. The advantages of this 3D printing-based method include (1) highly monodisperse capsules, (2) efficient encapsulation of biomolecular payloads, (3) precise spatial patterning of capsule arrays, (4) “on the fly” programmable reconfiguration of gradients, and (5) versatility for incorporation in hierarchical architectures. Indeed, 3D printing of programmable release capsules may represent a powerful new tool to enable spatiotemporal control over biomolecular gradients.

3D printed bionic nanodevices

“…2–10 2 mPa·s [51]), extrusion-based 3D printing is capable of incorporating a wide range of materials with viscosities up to 10 6 mPa·s and with disparate properties [47,61]. This versatility has enabled the accommodation of different classes of materials encompassing a wide range of length-scales: including nanomaterials [61,62], fibers [63], cells [64,65], tissues [66], organs [55,67], ceramics [68,69], metals [70] and polymers such as elastomers [59,60,71], gels [72,73], and biomaterials [55,74]. …”

“…We have developed an alternative strategy to 3D print highly monodisperse capsule arrays (Figure 7A) [62]. First, aqueous cores are printed onto a hydrophobic substrate.…”

“…We have demonstrated a novel, selectively photoresponsive system using our 3D printed capsule platform [62]. In order to make the capsules photoresponsive, we loaded the shells with gold nanorods.…”

“…Stimuli-responsive capsules and microfluidic networks are strategies for generating dynamic gradients that require novel materials and processes in order for them to be compatible with 3D printing. In order to 3D print complex arrays of stimuli responsive capsules, we have developed a new type of ink based on a water-in-oil emulsion [62,177–179]. The emulsion inks were prepared via high-speed dispersion of aqueous biomolecule solutions into a non-polar polymer solution.…”

Controlled release of curcumin from curcumin-loaded nanomicelles to prevent peritendinous adhesion during Achilles tendon healing in rats

“…Most importantly, curcumin release from GNRs-1/curc@PMs was controllable: 12 indeed, GNRs are considered particularly as attractive agents for hyperthermia-based treatments, and they were recently exploited for laser-induced and selective rupturing of polymeric capsule. 13,14 As we know, curcumin shows strong antioxidant and anti-inflammatory activities, and over 7,000 articles have discussed the molecular basis of curcumin's attributed antioxidant, anti-inflammatory, antibacterial, antiapoptosis, anticancer, and related activities in the past 2 decades. 15 In a rat tendon injury model, curcumin significantly improved the healing and function of injured tendon.…”