Presentation: 2025 ND EPSCoR Annual conference 

October 21, 2025, NDSU Memorial Union, Fargo, North Dakota

A hierarchically porous and SLIT3-releasing scaffold for bone tissue engineering applications

Large bone defects remain a critical clinical challenge, as current grafting techniques often fail to provide sufficient osteogenic support or long-term stability. One of the most fundamental requirements of a biomaterial for bone repair is its ability to mimic the native extracellular matrix, promote cell adhesion and proliferation, and deliver bioactive cues to stimulate regeneration. In this work, we present a functionalized, hierarchically porous nanocomposite scaffold engineered to release Slit Guidance Ligand 3 (SLIT3), a protein previously reported to enhance bone formation and modulate resorption during natural healing. Using indirect 3D printing, a polylactic-co-glycolic acid (PLGA)–hydroxyapatite nanoparticle–polydopamine (PLGA–HANPs–PDA) composite scaffold was fabricated and functionalized with SLIT3. The scaffold exhibited uniform chemical composition, a hierarchical microstructure with 63% porosity and an average pore size of 178.06 ± 45 µm, and mechanical properties including a compressive strength of up to 1.5 MPa at 75% strain and a modulus of 0.58 ± 0.05 MPa. Protein release studies confirmed gradual SLIT3 delivery into culture media, while preliminary biological assays demonstrated scaffold biodegradability, cytocompatibility, and support for mesenchymal stem cell (MSC) adhesion and proliferation. To our knowledge, this is the first report of SLIT3 bioactivity demonstrated within a PLGA–HANPs–PDA scaffold, highlighting its potential as a bone-mimicking platform for regenerative medicine. These findings establish a foundation for future targeted in vitro studies to evaluate osteogenic differentiation and bone regeneration potential.