ORIGINAL RESEARCH article
Front. Physiol.
Sec. Craniofacial Biology and Dental Research
Visible-Light–Triggered BMP-2 Release from Enzymatically Crosslinked Marine Collagen– Alginate Hydrogel Blends Enhances Osteogenesis in Dental Pulp Stem Cells
Provisionally accepted
- 1Department of Clinical Dentistry, University of Bergen, Bergen, Norway
- 2Microfluidic Innovation Centre, Paris, France
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Objectives: 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. Methods: 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. Results: 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). Conclusions: 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.
Keywords: alginate porogen, BMP-2, coumarinphotocage, dental pulp stem cells, Enzymatic crosslinking, Light-triggered release, Marine collagen, Osteogenesis
Received: 10 Nov 2025; Accepted: 26 Jan 2026.
Copyright: © 2026 Torelli. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Francesco Torelli
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