title: In vitro sustained release of recombinant human bone morphogenetic protein-2 microspheres embedded in thermosensitive hydrogels.
abstract: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a critical regulator of osteogenic capacity that is commonly used in bone grafts. The effectiveness of rhBMP-2 may be reduced as it can become unstable and degraded after injection into the body. Microspheres are considered appropriate vehicles for the sustained release of proteins in vivo. In this study, rhBMP-2 microspheres were manufactured using the water-in-oil-in-water (W/O/W) double-emulsion solvent-extraction technique by encapsulation in poly(lactic-co-glycolic) acid (PLGA). The microspheres were then embedded in two hydrogels made of either poloxamer 407 hydrogel or chitosan thioglycolic acid (CS-TA). The encapsulation efficiency and in vitro release of rhBMP-2 were examined and compared with the control release system (rhBMP-2 microspheres alone). The rhBMP-2 microspheres in the CS-TA hydrogel showed the lowest burst release (about 40% in the first 8h) among the three groups. The mechanisms may be the high viscosity of CS-TA hydrogel and the sustained release characteristics of CS-TA itself. The CS-TA hydrogel combined with PLGA microspheres can efficiently encapsulate rhBMP-2, control the burst release at early time points, and provide sustained release in vitro. It may be an appropriate rhBMP-2 vehicle for bone regeneration.
authors.affiliation: Orthopedics Department, General Hospital of Chinese PLA, Beijing, China.
authors.forename: Yangmu
authors.initials: Y
authors.lastname: Fu
authors.forename: Lina
authors.initials: L
authors.lastname: Du
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Weixiong
authors.initials: W
authors.lastname: Liao
authors.forename: Yiguang
authors.initials: Y
authors.lastname: Jin
authors.forename: Anjie
authors.initials: A
authors.lastname: Dong
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.forename: Zhongli
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D048271:Chitosan / Q000737:chemistry; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D020100:Hydrogels; D066298:In Vitro Techniques; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry; D012995:Solubility; D013696:Temperature; D013864:Thioglycolates / Q000737:chemistry; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D014783:Viscosity
chemical_list: D055396:Bone Morphogenetic Protein 2; D003692:Delayed-Action Preparations; D020100:Hydrogels; D011994:Recombinant Proteins; D013864:Thioglycolates; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; C017487:2-mercaptoacetate; D048271:Chitosan