Self-assembling peptide nanofibers as growth factor-mimicking scaffolds enhancing the bone regeneration potential of nanoceramics: a triad of in vitro, in vivo, and clinical trial studies

Abstract

Nano-tissue engineering utilizing self-assembling peptide nanofibers (SAPNs) offers a groundbreaking approach for repairing critical bone defects, overcoming the osteoinductive, angiogenic, and immunomodulatory limitations of traditional ceramic-based grafts. This study integrates in vitro, in vivo, and clinical trial evaluations to assess the bone regeneration potential of SAPNs combined with nanoceramics (nHA/TCP). FESEM revealed the structural characteristics of the SAPN (15–20 nm) and the distinct morphologies of nanoHA and β-TCP particles. In vitro results revealed the enhanced viability of MSCs and higher matrix mineralization and collagen production in the SAPN-nHA/TCP group compared to those in the nano-HA/TCP group. An in vivo study on critical-size bone defects in rats confirmed complete bone regeneration within 75 days in the SPAN nanoHA/TCP group, as evidenced by radiographic and histological evaluations. Gene expression analysis demonstrated the upregulation of osteogenic markers, including alkaline phosphatase, osteocalcin and BMP2. Conversely, the nHA/TCP group exhibited elevated Col1a1 expression, indicating ongoing connective tissue formation, reflecting a less mature stage of bone development relative to the fully ossified state observed in the SAPN-nHA/TCP group. Notably, a clinical trial involving socket preservation (IRCT20210526051407N2) demonstrated significant bone regeneration by 3.5 months post-implantation, with promising bone volume and density metrics. It underscores the real-world applicability of this approach in clinical settings, offering a highly effective solution for the restoration of bone defects that may not otherwise respond adequately to existing bone graft substitutes. These findings highlight SAPN's potential to enhance the bioactivity and osteogenic capacity of nanoceramic scaffolds, advancing bone tissue engineering for critical defect repair.