Bone regeneration via novel macroporous CPC scaffolds in critical-sized cranial defects in rats.
OBJECTIVE
Calcium phosphate cement (CPC) is promising for dental and craniofacial applications due to its ability to be injected or filled into complex-shaped bone defects and molded for esthetics, and its resorbability and replacement by new bone. The objective of this study was to investigate bone regeneration via novel macroporous CPC containing absorbable fibers, hydrogel microbeads and growth factors in critical-sized cranial defects in rats.


METHODS
Mannitol porogen and alginate hydrogel microbeads were incorporated into CPC. Absorbable fibers were used to provide mechanical reinforcement to CPC scaffolds. Six CPC groups were tested in rats: (1) control CPC without macropores and microbeads; (2) macroporous CPC+large fiber; (3) macroporous CPC+large fiber+nanofiber; (4) same as (3), but with rhBMP2 in CPC matrix; (5) same as (3), but with rhBMP2 in CPC matrix+rhTGF-β1 in microbeads; (6) same as (3), but with rhBMP2 in CPC matrix+VEGF in microbeads. Rats were sacrificed at 4 and 24 weeks for histological and micro-CT analyses.


RESULTS
The macroporous CPC scaffolds containing porogen, absorbable fibers and hydrogel microbeads had mechanical properties similar to cancellous bone. At 4 weeks, the new bone area fraction (mean±sd; n=5) in CPC control group was the lowest at (14.8±3.3)%, and that of group 6 (rhBMP2+VEGF) was (31.0±13.8)% (p<0.05). At 24 weeks, group 4 (rhBMP2) had the most new bone of (38.8±15.6)%, higher than (12.7±5.3)% of CPC control (p<0.05). Micro-CT revealed nearly complete bridging of the critical-sized defects with new bone for several macroporous CPC groups, compared to much less new bone formation for CPC control.


CONCLUSIONS
Macroporous CPC scaffolds containing porogen, fibers and microbeads with growth factors were investigated in rat cranial defects for the first time. Macroporous CPCs had new bone up to 2-fold that of traditional CPC control at 4 weeks, and 3-fold that of traditional CPC at 24 weeks, and hence may be useful for dental, craniofacial and orthopedic applications.
School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
Kangwon
K
Lee
Biomaterials & Tissue Engineering Division, Department of Endodontics, Prosthodontics and Operative Dentistry, University of Maryland School of Dentistry, Baltimore, MD 21201, USA.
Michael D
MD
Weir
School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
Evi
E
Lippens
School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
Manav
M
Mehta
Biomaterials & Tissue Engineering Division, Department of Endodontics, Prosthodontics and Operative Dentistry, University of Maryland School of Dentistry, Baltimore, MD 21201, USA.
Ping
P
Wang
Julius Wolff Institute, Charité - Universitätsmedizin Berlin and Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany.
Georg N
GN
Duda
School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
Woo S
WS
Kim
School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
David J
DJ
Mooney
Biomaterials & Tissue Engineering Division, Department of Endodontics, Prosthodontics and Operative Dentistry, University of Maryland School of Dentistry, Baltimore, MD 21201, USA; Center for Stem Cell Biology and Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Mechanical Engineering, University of Maryland, Baltimore County, MD 21250, USA. Electronic address: hxu@umaryland.edu.
Hockin H K
HH
Xu
D000818:Animals; D001861:Bone Regeneration; D002130:Calcium Phosphates; D003738:Dental Cements; D008422:Materials Testing; D016062:Porosity; D051381:Rats; D012886:Skull / Q000002:abnormalities*; D054457:Tissue Scaffolds
D002130:Calcium Phosphates; D003738:Dental Cements; C020243:calcium phosphate
Bone regeneration; Calcium phosphate cement; Critical-sized cranial defects; Growth factors; Macroporous scaffold; Strength and toughness