# Visible-light–triggered BMP-2 release from enzymatically crosslinked marine collagen–alginate hydrogel blends enhances osteogenesis in dental pulp stem cells

## TL;DR

A new hydrogel blend enables light-controlled release of BMP-2, enhancing bone growth in dental stem cells without harmful byproducts.

## Contribution

A visible-light–triggered, enzymatically crosslinked hydrogel system for controlled BMP-2 delivery and enhanced osteogenesis.

## Key findings

- Visible light triggered stepwise BMP-2 release (≈23% per pulse) with 60% cumulative release at 72 h.
- Alginate leaching created microporosity (20–60 µm) and increased oxygen diffusion by 42%.
- Light-pulsed composites showed 2.4-fold higher ALP activity and 2.8-fold more mineral deposition than controls.

## Abstract

Achieving spatiotemporal control over osteoinductive signaling remains a key challenge in craniofacial tissue engineering. Conventional BMP-2 delivery from photocrosslinked hydrogels often leads to uncontrolled burst release and cytotoxic by-products from radical initiators. Here, we designed an enzymatically crosslinked marine collagen–alginate hydrogel blend that enables visible-light–triggered, on-demand release of BMP-2 while promoting oxygen diffusion through leachable porosity.

Marine collagen functionalized with thiol groups (collagen-SH) was crosslinked by microbial transglutaminase (mTG) under physiological conditions, avoiding light-initiated polymerization. Recombinant BMP-2 was conjugated via a coumarin-based 405 nm–cleavable linker (BMP-2_pc) and covalently tethered to the collagen network. Non-crosslinked sodium alginate (0.6% w/v) was incorporated as a sacrificial porogen to create micropores upon diffusion. DPSC were encapsulated (1.5 × 106 cells/mL) and subjected to daily blue-LED pulses (405 ± 10 nm, 25 mW cm−2, 60 s) for up to 14 days. BMP-2 release (ELISA), porosity (SEM), oxygen diffusivity (Clark microelectrode), viability, and osteogenic differentiation (ALP, qPCR, Alizarin Red) were assessed.

Blue-light stimulation induced stepwise BMP-2 release (≈23% per pulse; 60% cumulative at 72 h), while mTG crosslinking preserved coumarin integrity. Alginate leaching generated an interconnected microporosity (20–60 µm pores) and increased oxygen diffusion coefficient by 42% ± 9%. DPSC viability remained >90%. Light-pulsed composites exhibited 2.4-fold ALP activity and 2.8-fold higher mineral deposition versus dark controls (p < 0.01).

The orthogonally crosslinked marine collagen–alginate composite supports visible-light–controlled BMP-2 delivery and oxygen-enhanced osteogenesis without photoinitiator toxicity. This platform provides a modular, sustainable route toward clinically programmable scaffolds for dental and craniofacial regeneration.