Reduction of ectopic bone growth in critically-sized rat mandible defects by delivery of rhBMP-2 from kerateine biomaterials.
Absorbable collagen sponges (ACS) are used clinically as carriers of recombinant human bone morphogenetic protein 2 (rhBMP-2) to promote bone regeneration. ACS exhibit ectopic bone growth due to delivery of supraphysiological levels of rhBMP-2, which is particularly problematic in craniofacial bone injuries for both functional and esthetic reasons. We hypothesized that hydrogels from the reduced form of keratin proteins (kerateine) would serve as a suitable alternative to ACS carriers of rhBMP-2. The rationale for this hypothesis is that keratin biomaterials degrade slowly in vivo, have modifiable material properties, and have demonstrated capacity to deliver therapeutic agents. We investigated kerateine hydrogels and freeze-dried scaffolds as rhBMP-2 carriers in a critically-sized rat mandibular defect model. ACS, kerateine hydrogels, and kerateine scaffolds loaded with rhBMP-2 achieved bridging in animals by 8 weeks as indicated by micro-computed tomography. Kerateine scaffolds achieved statistically increased bone mineral density compared to ACS and kerateine hydrogels, with levels reaching those of native bone. Importantly, both kerateine hydrogels and kerateine scaffolds had significantly less ectopic bone growth than ACS sponges at both 8 and 16 weeks post-operatively. These studies demonstrate the suitability of keratins as rhBMP-2 carriers due to equal regenerative capacity with reduced ectopic growth compared to ACS.
Department of Chemical, Paper, and Biomedical Engineering, Miami University, 650 E. High St., Oxford, OH 45056, USA; School of Biomedical Engineering and Sciences, Virginia Tech-Wake Forest University, Medical Center Blvd, Winston-Salem, NC 27157, USA.
Christine J
CJ
Kowalczewski
KeraNetics, LLC, Richard Dean Biomedical Research Building, Suite 168, 391 Technology Way, Winston-Salem, NC 27101, USA.
Seth
S
Tombyln
Department of Chemical, Paper, and Biomedical Engineering, Miami University, 650 E. High St., Oxford, OH 45056, USA.
David C
DC
Wasnick
Department of Statistics, Miami University, 311 Upham Hall, 501 E. High St., Oxford, OH 45056, USA.
Michael R
MR
Hughes
KeraNetics, LLC, Richard Dean Biomedical Research Building, Suite 168, 391 Technology Way, Winston-Salem, NC 27101, USA.
Mary D
MD
Ellenburg
Animal Health Specialties, LLC, MU Life Sciences Business Incubator at Monsanto Place, 1601 South Providence Road, Columbia, MO 65211, USA.
Michael F
MF
Callahan
Department of Orthopaedic Surgery, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
Thomas L
TL
Smith
School of Biomedical Engineering and Sciences, Virginia Tech-Wake Forest University, 317 Kelly Hall, Stanger St, Blacksburg, VA 24061, USA.
Mark E
ME
Van Dyke
KeraNetics, LLC, Richard Dean Biomedical Research Building, Suite 168, 391 Technology Way, Winston-Salem, NC 27101, USA.
Luke R
LR
Burnett
Department of Chemical, Paper, and Biomedical Engineering, Miami University, 650 E. High St., Oxford, OH 45056, USA. Electronic address: sauljm@MiamiOH.edu.
Justin M
JM
Saul
D000818:Animals; D001672:Biocompatible Materials; D001846:Bone Development; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage*; D001861:Bone Regeneration; D007633:Keratins / Q000737:chemistry*; D008297:Male; D008334:Mandible / Q000002:abnormalities*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage; D012212:Rheology; D054457:Tissue Scaffolds
C525718:BMP2 protein, human; D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D007633:Keratins
Bone regeneration; Collagen; Hydrogel; In vivo test; Keratin; Scaffold