BMP2‐mimicking peptide modified with E7 coupling to calcined bovine bone enhanced bone regeneration associating with activation of the Runx2/SP7 signaling axis
Abstract:Commercial bone substitute, such as calcined bovine bone (CBB), is currently extensively used as an alternative to autogenous bone. However, CBB lacks osteoinductivity and merely serves as a scaffold for native bone formation. To address this issue, we designed and prepared a heptaglutamate (E7)‐modified BMP2‐mimicking peptide (7E) and carried out a series of comprehensive physical characterizations and in vivo and in vitro studies to evaluate its role in the repair of cranial defects. The data elucidated that… Show more
“…e differentiation of osteoblasts in RUNX2 deficient mice is completely inhibited, and periosteal osteogenesis and endochondral osteogenesis do not occur [23]. Sp7 (osteoblast-specific transcription factor osterix) belongs to the SP/xklf family, which is expressed specifically in developing bone tissue and is a necessary transcription factor in osteoblast differentiation and bone formation [24]. According to western blot results, the PLGA scaffold of peptide hydrogel promoted the proliferation and differentiation of rat BMSCs cells and osteogenic induction.…”
Objective. To prepare a three-dimensional (3D) printing polylactic acid glycolic acid (PLGA) scaffold with bone morphogenetic protein-9 (BMP-9) and P-15 peptide hydrogel and evaluate its application in treating bone defects in rabbits. Methods. 3D printing PLGA scaffolds were formed and scanned by electron microscopy. Their X-ray diffraction (XRD), in vitro degradation, and compressive strength were characterized. BMP-9 and P-15 hydrogels were prepared. Flow cytometry was used to detect apoptosis, and an electron microscope was used to evaluate cell adhesion to scaffolds. Alkaline phosphatase (ALP), type 1 collagen (Col-I), osteocalcin (OCN), runt-related transcription factor 2 (RUNX2), and osterix (SP7) were detected by western blotting. MicroCT was used to detect new bone formation, and bone tissue-related protein expressions were determined in the rabbit model with bone defects. Results. The 3D printing scaffolds were cylindrical, and the inner diameter of the scaffolds was about 1 mm. The bread peak with wide distribution showed that the 3D printing only involved a physical change, which did not change the properties of the materials. The degradation rate of scaffolds was 9.38%, which met the requirements of properties of biological scaffolds. The water absorption of the support was about 9.09%, and the compressive strength was 15.83 N/mm2. In the coculture of bone marrow mesenchymal stem cells (BMSCs) with scaffolds, the 2% polypeptide hydrogel showed the most obvious activity in promoting the differentiation of BMSCs. Flow cytometry showed that the 0% and 2% groups did not cause obvious apoptosis compared with the control group. Scaffolds with 2% and 4% polypeptide promoted the expression of ALP, COL-1, OCN, RUNX2, and Sp7 in BMSCs. In vivo experiments showed that the expression of ALP, COL-1, OCN, RUNX2, and Sp7 protein in the 2% polypeptide scaffold group increased significantly compared with the model group. MicroCT detection demonstrated that the 2% polypeptide scaffold had good bone repair ability. Conclusion. The PLGA scaffolds combined with BMP-9 and P-15 peptide hydrogels had good biological and mechanical properties and could repair bone defects in rabbits.
“…e differentiation of osteoblasts in RUNX2 deficient mice is completely inhibited, and periosteal osteogenesis and endochondral osteogenesis do not occur [23]. Sp7 (osteoblast-specific transcription factor osterix) belongs to the SP/xklf family, which is expressed specifically in developing bone tissue and is a necessary transcription factor in osteoblast differentiation and bone formation [24]. According to western blot results, the PLGA scaffold of peptide hydrogel promoted the proliferation and differentiation of rat BMSCs cells and osteogenic induction.…”
Objective. To prepare a three-dimensional (3D) printing polylactic acid glycolic acid (PLGA) scaffold with bone morphogenetic protein-9 (BMP-9) and P-15 peptide hydrogel and evaluate its application in treating bone defects in rabbits. Methods. 3D printing PLGA scaffolds were formed and scanned by electron microscopy. Their X-ray diffraction (XRD), in vitro degradation, and compressive strength were characterized. BMP-9 and P-15 hydrogels were prepared. Flow cytometry was used to detect apoptosis, and an electron microscope was used to evaluate cell adhesion to scaffolds. Alkaline phosphatase (ALP), type 1 collagen (Col-I), osteocalcin (OCN), runt-related transcription factor 2 (RUNX2), and osterix (SP7) were detected by western blotting. MicroCT was used to detect new bone formation, and bone tissue-related protein expressions were determined in the rabbit model with bone defects. Results. The 3D printing scaffolds were cylindrical, and the inner diameter of the scaffolds was about 1 mm. The bread peak with wide distribution showed that the 3D printing only involved a physical change, which did not change the properties of the materials. The degradation rate of scaffolds was 9.38%, which met the requirements of properties of biological scaffolds. The water absorption of the support was about 9.09%, and the compressive strength was 15.83 N/mm2. In the coculture of bone marrow mesenchymal stem cells (BMSCs) with scaffolds, the 2% polypeptide hydrogel showed the most obvious activity in promoting the differentiation of BMSCs. Flow cytometry showed that the 0% and 2% groups did not cause obvious apoptosis compared with the control group. Scaffolds with 2% and 4% polypeptide promoted the expression of ALP, COL-1, OCN, RUNX2, and Sp7 in BMSCs. In vivo experiments showed that the expression of ALP, COL-1, OCN, RUNX2, and Sp7 protein in the 2% polypeptide scaffold group increased significantly compared with the model group. MicroCT detection demonstrated that the 2% polypeptide scaffold had good bone repair ability. Conclusion. The PLGA scaffolds combined with BMP-9 and P-15 peptide hydrogels had good biological and mechanical properties and could repair bone defects in rabbits.
“…In the past, this material has been used as a suitable carrier for delivering ions, biomolecules, and drugs. [14][15][16] TBC eliminates the original immunogenicity during high-temperature calcination, retaining the original natural three-dimensional (3D) pore structure and good mechanical strength while being more easily degradable than hydroxyapatite (HA). 17 The porous surface structure provides space for osteoblast anchoring and the inward growth of bone tissue, improving osseointegration and mechanical interlocking and preventing implant failure by improving mechanical interlocking at the bone/implant interface.…”
Bone defects are one of the toughest challenges faced by orthopedic surgeons worldwide, especially at critical sizes, which are caused by severe trauma, malignancy, or congenital disease. The ideal bone...
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