Porous silicon carriers for bone morphogenic protein-2 integrated in personalized 3D-printed bone grafts

Yuexi Lin ¹ Dekel Shilo ^2,3 Tal Capucha ² Karim Tarabieh ² Adi Rachmiel ^2,3 Ester Segal ^1,4

¹Department of Biotechnology and Food Engineering, Technion—Israel Institute of Technology, Israel
²Department of Oral and Maxillofacial Surgery, Rambam Health Care Campus, Israel
³Bruce Rappaport Faculty of Medicine, Technion—Israel Institute of Technology, Israel
⁴Russel Berrie Nanotechnology Institute, Technion—Israel Institute of Technology, Israel

The incorporation of bone morphogenetic protein-2 (BMP-2), which is a potent osteogenic factor, into three-dimensional (3D)-printed bone grafts, represents a promising strategy for enhancing bone regeneration. BMP-2 activity in implant sites is currently limited due to its poor stability, short half-life, and burst release patterns from conventional collagen scaffolds [1]. Herein, we develop degradable porous silicon (PSi)-based carriers which serve as BMP-2 reservoirs and allow for the protein’s sustained and prolonged release while retaining its biological activity. The PSi nanostructure is optimized to allow a high loading capacity of >20 μg/cm2 and preserve the bioactivity of the protein for inducing osteogenic differentiation. In vitro release studies show that PSi carriers exhibit a sustained release of BMP-2, without a burst effect, over a period of one month. These carriers are then incorporated in a sophisticated 3D printed patient-specific implant, which is made from a composite of poly(caprolactone), bone particles, and PSi microparticles. The integrated grafts are used to repair craniomaxillofacial bone defects using in vivo rabbit mandible defect model for a period of 12 weeks.

[1]. James AW, LaChaud G, Shen J, et al. A Review of the Clinical Side Effects of Bone Morphogenetic Protein-2. Tissue Eng - Part B Rev. 2016;22(4):284-297.