Modeling vascularized bone regeneration within a porous biodegradable CaP scaffold loaded with growth factors

被引:86
作者
Sun, Xiaoqiang [1 ,2 ]
Kang, Yunqing [3 ]
Bao, Jiguang [1 ]
Zhang, Yuanyuan [4 ]
Yang, Yunzhi [3 ]
Zhou, Xiaobo [2 ]
机构
[1] Beijing Normal Univ, Sch Math Sci, Beijing 100875, Peoples R China
[2] Wake Forest Univ, Bowman Gray Sch Med, Dept Radiol, Winston Salem, NC 27157 USA
[3] Stanford Univ, Dept Orthoped Surg, Stanford, CA 94305 USA
[4] Wake Forest Univ, Bowman Gray Sch Med, Wake Forest Inst Regenerat Med, Winston Salem, NC 27157 USA
关键词
3D system modeling; Bone regeneration; Porous biodegradable scaffold; Growth factor release; Signaling pathway; Angiogenesis; TISSUE-ENGINEERED BONE; TRICALCIUM PHOSPHATE; DUAL DELIVERY; PREDICTION; POROSITY; RELEASE; OSTEOINTEGRATION; HYDROXYAPATITE; MICROSPHERES; PERFORMANCE;
D O I
10.1016/j.biomaterials.2013.03.015
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Osteogenetic microenvironment is a complex constitution in which extracellular matrix (ECM) molecules, stem cells and growth factors each interact to direct the coordinate regulation of bone tissue development. Importantly, angiogenesis improvement and revascularization are critical for osteogenesis during bone tissue regeneration processes. In this study, we developed a three-dimensional (3D) multiscale system model to study cell response to growth factors released from a 3D biodegradable porous calcium phosphate (Cap) scaffold. Our model reconstructed the 3D bone regeneration system and examined the effects of pore size and porosity on bone formation and angiogenesis. The results suggested that scaffold porosity played a more dominant role in affecting bone formation and angiogenesis compared with pore size, while the pore size could be controlled to tailor the growth factor release rate and release fraction. Furthermore, a combination of gradient VEGF with BMP2 and Wnt released from the multi-layer scaffold promoted angiogenesis and bone formation more readily than single growth factors. These results demonstrated that the developed model can be potentially applied to predict vascularized bone regeneration with specific scaffold and growth factors. Published by Elsevier Ltd.
引用
收藏
页码:4971 / 4981
页数:11
相关论文
共 62 条
[1]   Smad function and intranuclear targeting share a Runx2 motif required for osteogenic lineage induction and BMP2 responsive transcription [J].
Afzal, F ;
Pratap, J ;
Ito, K ;
Ito, Y ;
Stein, JL ;
Van Winen, AJ ;
Stein, GS ;
Lian, JB ;
Javed, A .
JOURNAL OF CELLULAR PHYSIOLOGY, 2005, 204 (01) :63-72
[2]  
Alam MI, 2001, BIOMATERIALS, V22, P1643
[3]   Mathematical modeling and simulation of drug release from microspheres: Implications to drug delivery systems [J].
Arifin, Davis Yohanes ;
Lee, Lai Yeng ;
Wang, Chi-Hwa .
ADVANCED DRUG DELIVERY REVIEWS, 2006, 58 (12-13) :1274-1325
[4]  
Artel A, 2011, TISSUE ENG PT A, V17, P2133, DOI [10.1089/ten.tea.2010.0571, 10.1089/ten.TEA.2010.0571]
[5]   Effect of cell seeding and mechanical loading on vascularization and tissue formation inside a scaffold: A mechano-biological model using a lattice approach to simulate cell activity [J].
Checa, Sara ;
Prendergast, Patrick J. .
JOURNAL OF BIOMECHANICS, 2010, 43 (05) :961-968
[6]   A Mechanobiological Model for Tissue Differentiation that Includes Angiogenesis: A Lattice-Based Modeling Approach [J].
Checa, Sara ;
Prendergast, Patrick J. .
ANNALS OF BIOMEDICAL ENGINEERING, 2009, 37 (01) :129-145
[7]   Designing Bioactive Delivery Systems for Tissue Regeneration [J].
Davis, Hillary E. ;
Leach, J. Kent .
ANNALS OF BIOMEDICAL ENGINEERING, 2011, 39 (01) :1-13
[8]   Growth factors in bone repair. [J].
Devescovi V. ;
Leonardi E. ;
Ciapetti G. ;
Cenni E. .
La Chirurgia degli Organi di Movimento, 2008, 92 (3) :161-168
[9]   Tissue-engineered bone from BMP-2-transduced stem cells derived from human fat [J].
Dragoo, JL ;
Lieberman, JR ;
Lee, RS ;
Deugarte, DA ;
Lee, Y ;
Zuk, PA ;
Hedrick, MH ;
Benhaim, P .
PLASTIC AND RECONSTRUCTIVE SURGERY, 2005, 115 (06) :1665-1673
[10]   Linking measured intercellular oxygen concentration to human cell functions [J].
Ebbesen, P ;
Eckardt, KU ;
Ciampor, F ;
Pettersen, EO .
ACTA ONCOLOGICA, 2004, 43 (06) :598-600