title: Rapid healing of femoral defects in rats with low dose sustained BMP2 expression from PEGDA hydrogel microspheres.
abstract: Current strategies for bone regeneration after traumatic injury often fail to provide adequate healing and integration. Here, we combined the poly (ethylene glycol) diacrylate (PEGDA) hydrogel with allogeneic "carrier" cells transduced with an adenovirus expressing BMP2. The system is unique in that the biomaterial encapsulates the cells, shielding them and thus suppressing destructive inflammatory processes. Using this system, complete healing of a 5 mm-long femur defect in a rat model occurs in under 3 weeks, through secretion of 100-fold lower levels of protein as compared to doses of recombinant BMP2 protein used in studies which lead to healing in 2-3 months. New bone formation was evaluated radiographically, histologically, and biomechanically at 2, 3, 6, 9, and 12 weeks after surgery. Rapid bone formation bridged the defect area and reliably integrated into the adjacent skeletal bone as early as 2 weeks. At 3 weeks, biomechanical analysis showed the new bone to possess 79% of torsional strength of the intact contralateral femur. Histological evaluation showed normal bone healing, with no infiltration of inflammatory cells with the bone being stable approximately 1 year later. We propose that these osteoinductive microspheres offer a more efficacious and safer clinical option over the use of rhBMP2.
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, One Baylor Plaza, Alkek Building, Room N1010, Houston, Texas 77030, USA.
authors.forename: Corinne
authors.initials: C
authors.lastname: Sonnet
authors.forename: C Lashan
authors.initials: CL
authors.lastname: Simpson
authors.forename: Ronke M
authors.initials: RM
authors.lastname: Olabisi
authors.forename: Kayleigh
authors.initials: K
authors.lastname: Sullivan
authors.forename: Zawaunyka
authors.initials: Z
authors.lastname: Lazard
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Gugala
authors.forename: John F
authors.initials: JF
authors.lastname: Peroni
authors.forename: J Michael
authors.initials: JM
authors.lastname: Weh
authors.forename: Alan R
authors.initials: AR
authors.lastname: Davis
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: West
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Olmsted-Davis
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects / Q000502:physiology; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004339:Drug Compounding / Q000379:methods; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D005269:Femur / Q000187:drug effects / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology; D017102:Fracture Healing / Q000187:drug effects* / Q000502:physiology; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology; D008863:Microspheres; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011859:Radiography; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000166:cytology; D017154:Stromal Cells / Q000166:cytology
chemical_list: C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; C437167:poly(ethylene glycol)diacrylate; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols
keywords: BMP2; PEGDA; bone healing; critical size defect; microencapsulation