Additive manufacturing of hydrogel-based materials for next-generation implantable medical devices

Abstract

Implantable microdevices often have static components rather than moving parts, and exhibit limited biocompatibility. This paper demonstrates a fast manufacturing method which can produce features in biocompatible materials down to tens of microns in scale, with intricate and composite patterns in each layer. By exploiting unique mechanical properties of hydrogels, we developed a “locking mechanism” for precise actuation and movement of freely moving parts, which can provide functions such as valves, manifolds, rotors, pumps, and delivery of payloads. Hydrogel components could be tuned within a wide range of mechanical and diffusive properties, and can be controlled after implantation without a sustained power supply. In a mouse model of osteosarcoma, triggering of release of doxorubicin from the device over ten days showed high treatment efficacy and low toxicity, at one-tenth of a standard systemic chemotherapy dose. Overall, this platform, called “iMEMS”, enables development of biocompatible implantable microdevices with a wide range of intricate moving components that can be wirelessly controlled on demand, in a manner that solves issues of device powering and biocompatibility.

Muscle-like fatigue-resistant hydrogels by mechanical training

“…Moreover, despite their high water content of around 75 wt % (3), skeletal muscles can sustain a high stress of 1 MPa over 1 million cycles per year, with a fatigue resistance over 1,000 J/m 2 (4). The combinational properties of skeletal muscles (i.e., high fatigue resistance, high strength, superior compliance, and high water content) are highly desirable for hydrogels' nascent applications in soft biological devices, such as load-bearing artificial tissues (5), hydrogel bioelectronics (6-9), hydrogel optical fibers (10, 11), ingestible hydrogel devices (12), robust hydrogel coatings on medical devices (13-17), and hydrogel soft robots (18)(19)(20).Although various molecular and macromolecular engineering approaches have replicated parts of biological muscles' characteristics, none of them can synergistically replicate all these attributes in one single material system (SI Appendix, Table S1). For example, both strain-stiffening hydrogels (21, 22) and bottle brush polymer networks (1, 23) can mimic the J-shaped stress− strain behaviors, but their fracture toughness is still much lower than biological tissues, since no significant mechanical dissipation has been introduced in these materials for toughness enhancement.…”

Biohybrid Design Gets Personal: New Materials for Patient‐Specific Therapy

“…In addition to the stimuli discussed above as potential environmental triggers of predefined functions, a range of other stimuli, such as magnetic fields, electrical fields, and ultrasound waves, have also been investigated as potential mechanisms for evoking hydrogel response . For example, a recent study by Chin et al demonstrated that a PEG‐based implantable device doped with iron oxide nanoparticles could be controlled externally via a magnet to release drug payloads on demand . Similarly, we have demonstrated that encapsulating superparamagnetic iron oxide nanoparticles (SPIONs) in a PEG‐based gel can enhance magnetic resonance contrast .…”

Additive Manufacturing of Precision Biomaterials

“…The concepts of digital design and fabrication of DDS has been extended beyond classic pharmaceutical dosage forms and conformal controlled release devices. For example, an implantable micro‐electromechanical system (MEMS), mainly composed of PEGDA, was fabricated via SLA and microfabrication . Iron nanoparticles were incorporated into the system, making it responsive to magnetic stimuli.…”