Kangwon Lee1, Michael D Weir2, Evi Lippens1, Manav Mehta1, Ping Wang2, Georg N Duda3, Woo S Kim1, David J Mooney1, Hockin H K Xu4. 1. School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA. 2. Biomaterials & Tissue Engineering Division, Department of Endodontics, Prosthodontics and Operative Dentistry, University of Maryland School of Dentistry, Baltimore, MD 21201, USA. 3. Julius Wolff Institute, Charité - Universitätsmedizin Berlin and Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany. 4. 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.
Abstract
OBJECTIVES: 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. SIGNIFICANCE: 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.
OBJECTIVES: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. SIGNIFICANCE: Macroporous CPC scaffolds containing porogen, fibers and microbeads with growth factors were investigated in ratcranial 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.
Authors: Howard J Seeherman; Kodi Azari; Sean Bidic; Leif Rogers; X Jian Li; Jeffrey O Hollinger; John M Wozney Journal: J Bone Joint Surg Am Date: 2006-07 Impact factor: 5.284
Authors: Jeremy J Mao; Michael S Stosich; Eduardo K Moioli; Chang Hun Lee; Susan Y Fu; Barbara Bastian; Sidney B Eisig; Candice Zemnick; Jeffrey Ascherman; June Wu; Christine Rohde; Jeffrey Ahn Journal: Tissue Eng Part B Rev Date: 2010-04 Impact factor: 6.389
Authors: Stephen Kennedy; Charles Roco; Alizée Déléris; Patrizia Spoerri; Christine Cezar; James Weaver; Herman Vandenburgh; David Mooney Journal: Biomaterials Date: 2018-02-03 Impact factor: 12.479
Authors: Chen Shen; Lukasz Witek; Roberto L Flores; Nick Tovar; Andrea Torroni; Paulo G Coelho; F Kurtis Kasper; Mark Wong; Simon Young Journal: Tissue Eng Part A Date: 2020-10-01 Impact factor: 3.845
Authors: Sophia P Pilipchuk; Alexandra B Plonka; Alberto Monje; Andrei D Taut; Alejandro Lanis; Benjamin Kang; William V Giannobile Journal: Dent Mater Date: 2015-02-18 Impact factor: 5.304
Authors: Ping Wang; Yang Song; Michael D Weir; Jinyu Sun; Liang Zhao; Carl G Simon; Hockin H K Xu Journal: Dent Mater Date: 2015-12-29 Impact factor: 5.304
Authors: Hong Chen; Hui Yang; Michael D Weir; Abraham Schneider; Ke Ren; Negar Homayounfar; Thomas W Oates; Ke Zhang; Jin Liu; Tao Hu; Hockin H K Xu Journal: RSC Adv Date: 2020-11-04 Impact factor: 4.036
Authors: Sundus Iftikhar; Noureen Jahanzeb; Mehvish Saleem; Shafiq Ur Rehman; Jukka Pekka Matinlinna; Abdul Samad Khan Journal: Saudi Dent J Date: 2021-01-14