Granular, Hierarchically Porous Polymer Scaffolds for Bone Tissue Engineering

Bone fractures arising from trauma, infection, tumors, osteoporosis, or congenital malformations remain a significant clinical and economic burden, with current implant strategies limited by poor durability, inadequate integration, infection risk, and insufficient support for complex defect geometries. The management of critical-size bone defects continues to pose major challenges for orthopedic and reconstructive surgeons and patients worldwide, underscoring the need for new therapeutic approaches. Conventional bulk or block scaffolds are constrained by their inability to conform precisely to irregular defect morphologies, limiting their effectiveness. To address these limitations, we developed granular, hierarchically porous, emulsion-templated (polyHIPE) scaffolds using UV-initiated photopolymerization of trimethylolpropane tris(3‑mercaptopropionate) (TMPTMP) and dipentaerythritol penta/hexa‑acrylate (DPEHA), incorporating 3D‑printed, water‑soluble poly(vinyl alcohol) (PVA) lattices to generate defined 500 µm channels. Comparative analysis of channeled and non‑channeled granules revealed distinct morphological features; SEM imaging showed average void diameters of 18.2 ± 1.1 µm in non‑channeled particles and 24.3 ± 1.4 µm in channeled particles, while mercury intrusion porosimetry confirmed 3–4 µm interconnects and overall porosity exceeding 80%. Skeletal density measured by helium pycnometry was 1.4 g/cm³, with granule yields ≥84% for particles ≥500 µm. Biological evaluation using MG63 osteosarcoma cells cultured on channeled particles in a Vertical Wheel Bioreactor® demonstrated comparable proliferation and infiltration, supported by immunofluorescence, live/dead staining, resazurin assays, and H&E analysis. The 500 µm polyHIPE granules, combined with optimized bioreactor systems, forge a powerful moldable scaffold platform ideally suited for minimally invasive reconstruction of complex, irregular bone defects.