BMP7-Based Functionalized Self-Assembling Peptides for Nucleus Pulposus Tissue Engineering

Nucleus pulposus (NP) tissue engineering has been demonstrated to be a feasible therapeutic strategy for intervertebral disc regeneration. In this study, we constructed a novel injectable biomaterial by conjugating three different short peptides of BMP7 to the C-terminus of the self-assembling peptide RADA16-I, and we then mixed each of these conjugates with RADA16-I at equal volumes to obtain the novel functionalized peptides RAD-SNV, RAD-KPS, and RAD-KAI. The bioactivities of these functionalized peptides for human degenerated NP cells (hdNPCs) were evaluated in vitro, and the most ideal scaffold was chosen for assessment of its in vivo degradation and the tissue reactions to it. All of the functionalized peptides self-assembled to form hydrogel scaffolds with a nanofibrous structure under physiological conditions. Compared with the RADA16-I and RAD-KAI scaffolds, the RAD-SNV and RAD-KPS scaffolds possessed better bioactivities for hdNPCs, which were characterized by their enhanced proliferation, migration, and ECM (collagen II, aggrecan, and sox-9) secretion. RAD-KPS was chosen over RAD-SNV as the most ideal scaffold material due to the cells' higher rate of expression of aggrecan both at the gene and protein level after 28 days of coculture. Moreover, in vivo analysis demonstrated that subcutaneously injected RAD-KPS degraded in vivo without invoking intense inflammation. Therefore, RAD-KPS is an ideal candidate scaffold for NP tissue engineering and holds great potential for NP regeneration.