Evaluation of osteogenic inductivity of a novel BMP2‐mimicking peptide P28 and P28‐containing bone composite

Abstract

We developed a novel BMP2-mimicking peptide P28, which possesses two distinct special structural elements-seven repetitive aspartic acids and phosphorylated serine designed to promote affinity to hydroxyapatite as well as nucleation of apatite crystallization and mineralization. In this work, we systematically studied the osteogenic inductivity of P28 in vitro and in vivo in comparison with BMP2. We confirmed its effects on proliferation, recruitment, and osteogenic differentiation of MC3T3-E1 cells in vitro. Furthermore, we loaded P28 into a biomimetic bone composite nanohydroxyapatite/collagen/poly(L-lactide) (nHAC/PLA) and evaluated its ability to promote bone regeneration in vivo using a rabbit femoral condyle defect model. The micro-CT reconstruction and quantification analysis and the histological analysis indicated that P28/nHAC/PLA bone composite was capable of repairing bone defects.

Sustained delivery of PlGF-2123-144*-fused BMP2-related peptide P28 from small intestinal submucosa/polylactic acid scaffold material for bone tissue regeneration

“…SIS/PLA was designed based on the principle of biomimetics, with both composition and structure being similar to natural bone. Its pore size of 100-300 mm may provide a superior structure: 25 macropores with a pore diameter in the range of 50-300 mm are required for cell penetration and neovascularization with a scaffold in vivo. Previous studies have demonstrated the outstanding biocompatibility and non-immunogenicity of SIS.…”

“…This suggests that the enhanced material retention and lower P28 concentration in bone tissue may improve the potency of P28 in exerting osteogenic bioactivity used in our previous study. 25 We then focused on verifying the biological activity of P28 and PlGF-2 123-144* fused P28 in subsequent cell and animal experiments. The effects of the scaffold material on cell behavior are a result of the interactions between the ligand on the scaffold surface and the receptors on the cells.…”

“…The P28 peptide was conrmed to display effects of bone formation similar to those of BMP-2 in a rat model. [24][25][26] In addition, the short block of seven repeated aspartic acid, linked to phosphorylated serine motifs, have a higher affinity to hydroxyapatite. In general, the growth factor would signicantly increase the rate of release and degradation in vivo, which are the key limiting factors in the translation of growth factors to clinical use in regenerative medicine.…”

Guided osteoporotic bone regeneration with composite scaffolds of mineralized ECM/heparin membrane loaded with BMP2-related peptide

“…In addition, P28 content was determined using high-performance liquid chromatography, as previously described. 27 To investigate the release kinetics of P28, mSIS/P28 (5×5×0.5 mm 3 ) with or without heparinization was incubated in 200 mL PBS at 37°C for 14 days. The eluted P28 peptide was quantified at day 0.5, 1, 3, 5, 7, 10, 14, 17, 21, 25, 29, 33, and 37 following incubation.…”

“…ARS staining was performed according to a previous study. 27 The optical density of Alizarin Red extracted from the samples was spectrophotometrically determined at 405 nm wavelength using a microplate reader.…”