Localization of Lesion Cells and Targeted Mitochondria Via Embedded Hydrogel Microsphere using Heat Transfer Microneedles

Abstract

The localization of lesion cells and targeted regulation of organelle function can promote the lesion repair. However, conventional regulation is difficult to reach deep lesions and target mitochondria. In this study, dynamic spiral Mosaic technology is ued to construct heat transfer microneedles with spiral Mosaic micro/nano hydrogel microspheres (ST-needle), using molecular chain motion in response to heat stimulation to regulate the adhesion of nonoriented triblock polymer, as a dual delivery system for heat energy and biological factors. The ST-needle system use its physical property to accurately reach the deep lesions and transfer heat to the lesion cells. Heat activates the dynamic spiral Mosaic mechanism of the ST-needle system, removing the Mosaic state of hydrogel microspheres and realizing the arrival of heat and hydrogel microspheres into lesion together. Through the rapid inhibition of mitochondrial apoptosis by heat, and long-term induce mitophagy by hydrogel microspheres releasing biological factors, finally complete the synergistic targeted regulation of mitochondrial function. In vitro/vivo experiments show that ST-needle system can inhibit chondrocyte apoptosis more effectively (64.41% lower than conventional regulation). Based on dynamic spiral Mosaic technique and the synergistic regulation of heat and biological factors, the ST-needle system is a promising method for lesion repair.

Positioning regulation of organelle network via Chinese microneedle

“…An ST-needle embedded with functionalized hydrogel microspheres was constructed to develop the ST-needle composite system. Using the molecular chain motion triggered by thermal response to adjust the adhesion property of a nonoriented triblock polymer, the system enables the dual-localized delivery of physical and biological factors ( 34 ). Drawing inspiration from conductive CA-needles, the combination of functionalized hydrogel microspheres and localized conductive microneedles facilitates the dual positioning regulation of electrical energy and the delivery of biological factors, which represents a previously unknown biomaterial system with notable developmental potential.…”

“…5B). We previously demonstrated that this system is capable of delivering functionalized hydrogel microspheres to lesion sites using a thermoelectric acupuncture instrument to activate the dynamic Van der Waals force mechanism ( 34 ). The use of the conductive ST-needle system enables minimally invasive insertion of the needle tip into the deep layer of cartilage, precise localization of the cartilage lesion, and release of electrical energy.…”

“…Subsequently, the siRNA-loaded nanoparticles were combined with hyaluronic acid methacrylate (HAMA) using microfluidic technology to prepare photocrosslinked functionalized hydrogel microspheres. Last, a previously developed thermosensitive adhesive gel was used to load the functionalized hydrogel microspheres onto the screw-threaded grooves of the ST-needle, followed by the construction of the conductive ST-needle system ( 33 , 34 ). With the dual protection of the screw-threaded grooves and adhesive gel, the conductive ST-needle system could successfully carry the functionalized hydrogel microspheres, penetrate the physical barrier, and deliver the microspheres to the lesion.…”

Retuning Mitochondrial Apoptosis/Mitophagy Balance via SIRT3‐Energized and Microenvironment‐Modulated Hydrogel Microspheres to Impede Osteoarthritis

“…Conjugating TPP with poly (D, L‐lactic acid ‐co‐ glycolic acid)‐poly (ethylene glycol)‐poly (D, L‐lactic acid ‐co‐ glycolic acid; PLGA–PEG–PLGA), a thermosensitive polymer, can release therapeutic agents (i.e., mitophagy inducer: Parkin protein) into the mitochondria at the deep cartilage and even the subchondral bone, controllably and accurately at the guidance heat energy. [ 59 ] The potential future prospects for OA could be an integration strategy equipped with hierarchical targetability and responsibility for the synergistic microenvironment regulation.…”

Transdermal drug delivery via microneedles for musculoskeletal systems

“…Lin et al designed heat transfer microneedles with spiral Mosaic micro/nanohydrogel microspheres (ST needles). 106 Hydrogel microspheres containing the biological factor PARKIN protein are loaded into the threaded groove of the ST needle using a thermosensitive adhesive triblock copolymer so that they can pass through the barrier of cartilage on the ST needle with the double protection provided by the threaded groove and the viscous polymer. In response to thermal stimulation with molecular chain motion, the hydrogel microspheres will detach from the needle body.…”