GelMA–pectin–polyhedral silsesquioxane nanocomposites for 3D bioprinting of osteogenesis-stimulating scaffolds loaded with BMP-2

Abstract

Harnessing the advantage of both naturally derived polymers and nanostructured materials, the current study presents a novel multicomponent hydrogel system double-reinforced with two complementary nanofillers, specifically designed for bioprinting-based tissue engineering applications. In a bioinspired approach, cellulose nanofibrils (CNFs) and polyhedral silsesquioxanes (PSS) nanoparticles were embedded in a proteinaceous–polysaccharidic matrix. To synthesize a robust platform for 3D bioprinting, methacrylate-modified biopolymers were ultraviolet-crosslinked, ensuring optimal conditions for cell encapsulation. The nanocomposite bioinks were supplemented with bone morphogenetic protein 2 (BMP-2), a potent osteogenic factor, to enhance the osteogenic differentiation of preosteoblasts. The 3D scaffold morphology was investigated, with a focus on PSS dispersion, porosity, and geometrical properties of the constructs. Swelling studies confirmed that all hydrogel samples retained their hydrophilic nature, though a slight reduction in swelling capacity was observed upon PSS incorporation. In vitro cytocompatibility tests demonstrated the beneficial effects of CNFs and PSS on cell growth. In vivo studies further revealed that hydrogels supplemented with nanostructured fillers and BMP-2 significantly enhanced osteogenesis, both in osteogenic and non-osteogenic regions. These findings prove that growth factor-reinforced scaffolds hold great potential in addressing the challenges of biomaterial research and represent a promising strategy for hard tissue regeneration.

Keywords

BMP-2 / Hybrid printing inks / In vivo osteogenesis / Nanocomposite hydrogels / Osteogenic induction

Funding

A. Lungu acknowledges support from the BIOPRINT project (GNAC ARUT 56/2023, ID 220235515), funded by the National Program for Research of the National Association of Technical Universities. I.C. Stancu and E. Olaret acknowledge support from the Next3DBone project (PN-III-P4-PCE-2021-1240, No. PCE 88/2022). The 3D printing and nanoindentation experiments were made possible through funding from the European Regional Development Fund via the Competitiveness Operational Program 2014-2020 (Priority axis 1, ID P_36_611, MySMIS code 107066, INOVABIOMED).

Conflict of interest

The authors declare they have no competing interests.

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