Immiscible Phase Separation-Driven Microfabrication of Gelatin Methacryloyl Scaffolds for BMP-2 Delivery and Osteogenic Enhancement.

Abstract

Gelatin methacryloyl (GelMA) hydrogels are recognized for their biocompatibility, tunable mechanics, and ability to support cellular functions, making them attractive for tissue engineering. However, achieving uniform, structurally stable micro-scaffolds for minimally invasive delivery remains challenging. Injectable hydrogels provide targeted delivery but lack the micro-architectural complexity required for effective regeneration, while 3D printing offers precision yet faces resolution, handling, and mechanical limitations. To overcome these barriers, we developed injectable GelMA micro-scaffolds (mS-GelMA) with controlled porosity, stability, and reproducibility using stop-flow lithography (SFL). This technique enables precise control over shape, porosity, and degradation, surpassing conventional injection moulding and 3D bioprinting in micro-particle uniformity and reproducibility. Scaffold performance was optimized by incorporating trimethylolpropane triacrylate (TMPTA) into GelMA, enhancing drug delivery and regenerative potential. Cellular assays confirmed high biocompatibility and functionality, with human mesenchymal stem cells (hMSCs) exhibiting excellent viability, migration, and osteogenic differentiation within the mS-GelMA scaffolds. These findings demonstrate that SFL-fabricated GelMA scaffolds bridge the gap between injectability and structural complexity, offering a promising platform for minimally invasive tissue engineering. This work highlights the potential of SFL-engineered hydrogels to advance scaffold-based regenerative medicine by combining architectural precision, biological performance, and clinical applicability.