Cholesteryl group- and acryloyl group-bearing pullulan nanogel to deliver BMP2 and FGF18 for bone tissue engineering.
To create a drug delivery system that allows the controlled release of proteins, such as growth factors, over a long-term period, cholesteryl group- and acryloyl group-bearing pullulan (CHPOA) nanogels were aggregated to form fast-degradable hydrogels (CHPOA/hydrogels) by cross-linking with thiol-bearing polyethylene glycol. The gold standard of clinical bone reconstruction therapy with a physiologically active material is treatment with recombinant human bone morphogenetic protein 2 (BMP2); however, this approach has limitations, such as inflammation, poor cost-efficiency, and varying interindividual susceptibility. In this study, two distinct growth factors, BMP2 and recombinant human fibroblast growth factor 18 (FGF18), were applied to a critical-size skull bone defect for bone repair by the CHPOA/hydrogel system. The CHPOA-FGF18/hydrogel displayed identical results to the control CHPOA-PBS/hydrogel, and the CHPOA-BMP2/hydrogel treatment imperfectly induced bone repair. By contrast, the CHPOA-FGF18 + BMP2/hydrogel treatment strongly enhanced and stabilized the BMP2-dependent bone repair, inducing osteoprogenitor cell infiltration inside and around the hydrogel. This report indicates that the CHPOA/hydrogel system can successfully deliver two different proteins to the bone defect to induce effective bone repair. The combination of the CHPOA/hydrogel system with the growth factors FGF18 and BMP2 might be a step towards efficient bone tissue engineering.
Section of Molecular Craniofacial Embryology, Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences, Tokyo, Japan.
Masako
M
Fujioka-Kobayashi
Masato S
MS
Ota
Asako
A
Shimoda
Ken-ichi
K
Nakahama
Kazunari
K
Akiyoshi
Youji
Y
Miyamoto
Sachiko
S
Iseki
D000179:Acrylates / Q000737:chemistry*; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D019070:Cell Lineage / Q000187:drug effects; D002784:Cholesterol / Q000737:chemistry*; D016503:Drug Delivery Systems; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D005936:Glucans / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D000080385:Nanogels; D010006:Osteoblasts / Q000187:drug effects / Q000473:pathology; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D011994:Recombinant Proteins / Q000494:pharmacology; D012235:Rhodamines / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods*; D014057:Tomography, X-Ray Computed; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects
D000179:Acrylates; D055396:Bone Morphogenetic Protein 2; D005936:Glucans; D000080385:Nanogels; D011994:Recombinant Proteins; D012235:Rhodamines; D016212:Transforming Growth Factor beta; C113569:fibroblast growth factor 18; C413692:polyethylene glycol polyethyleneimine nanogel; C499469:recombinant human bone morphogenetic protein-2; D011092:Polyethylene Glycols; D005346:Fibroblast Growth Factors; C009109:pullulan; D011094:Polyethyleneimine; D002784:Cholesterol; C036658:acrylic acid