Near-infrared light-responsive upconversion substrate enables spatiotemporal control of mesenchymal stem cells adhesion and multilineage differentiation in vivo

TL;DR

A new platform uses near-infrared light to control stem cell behavior and differentiation in living organisms with high precision.

Contribution

A novel NIR-responsive upconversion system enables spatiotemporal control of MSC adhesion and differentiation via mechanotransduction pathways in vivo.

Findings

Low NIR intensity promotes osteogenic differentiation with 2–3 fold upregulation of osteogenic markers.

High NIR intensity triggers adipogenic differentiation with 4–5 fold induction of adipogenic markers.

In vivo studies confirm spatiotemporal regulation of MSC fate and YAP signaling via NIR-controlled RGD ligand density.

Abstract

Spatiotemporally precise control of mesenchymal stem cells (MSCs) differentiation remains an unmet challenge in regenerative medicine. Herein, we report a near-infrared (NIR)-responsive platform that integrates upconversion nanoparticle (UCNP)-functionalized substrates with host-guest photoresponsive chemistry (β-cyclodextrin/arylazopyrazole-RGD) to NIR spatiotemporally orchestrate MSCs adhesion, spreading, and lineage commitment with spatiotemporal precision. The UCNPs convert 808 nm NIR light into localized UV emissions, dynamically modulating azobenzene-cyclodextrin interactions and thereby tuning surface RGD ligand density via photoisomerization. Under low NIR intensities (0–0.5 W/cm2), augmented integrin-RGD binding drives robust focal adhesion assembly, actin cytoskeletal tension, nuclear YAP translocation, and osteogenic differentiation, as evidenced by 2–3 fold upregulation of BMP2, RUNX2, and ALP. Conversely, high-intensity NIR (1–2 W/cm2) induces RGD detachment, leading to suppressed cytoskeletal contractility and nuclear Lamin A/C expression, consequent cytoplasmic YAP retention, and activation of PPARγ-mediated adipogenesis, marked by 4–5 fold induction of PPARγ, C/EBPα, and FABP4. Most importantly, in vivo murine studies validate the platform's capacity for non-invasive, light-guided spatiotemporal regulation of MSCs adhesion, spreading, YAP signaling, and lineage specification (osteogenic vs. adipogenic), wherein differentiation thresholds (e.g., 1 W/cm2) correspond to clinically safe NIR exposure limits. This opto-material hybrid system effectively decouples photochemical stimulation to program MSC fate via mechanotransduction pathways, thereby providing a translatable strategy for the design of intelligent biomaterials towards personalized tissue regeneration.

1. A near-infrared (NIR)-responsive upconversion platform controls surface RGD ligand density via host-guest chemistry. 2. NIR intensity spatiotemporally regulates the MSC mechanotransduction (YAP signaling) pathway in vivo. 3. Low NIR power induces osteogenic differentiation; high NIR power switches commitment to adipogenic differentiation.Image 1

Figures