Current advances for bone regeneration based on tissue engineering strategies
Rui Shi1, Yuelong Huang2, Chi Ma1, Chengai Wu1, Wei Tian1,2()
1. Institute of Traumatology and Orthopaedics, Beijing Laboratory of Biomedical Materials, Beijing Jishuitan Hospital, Beijing 100035, China 2. Department of Spine Surgery of Beijing Jishuitan Hospital, The Fourth Clinical Medical College of Peking University, Beijing 100035, China
Bone tissue engineering (BTE) is a rapidly developing strategy for repairing critical-sized bone defects to address the unmet need for bone augmentation and skeletal repair. Effective therapies for bone regeneration primarily require the coordinated combination of innovative scaffolds, seed cells, and biological factors. However, current techniques in bone tissue engineering have not yet reached valid translation into clinical applications because of several limitations, such as weaker osteogenic differentiation, inadequate vascularization of scaffolds, and inefficient growth factor delivery. Therefore, further standardized protocols and innovative measures are required to overcome these shortcomings and facilitate the clinical application of these techniques to enhance bone regeneration. Given the deficiency of comprehensive studies in the development in BTE, our review systematically introduces the new types of biomimetic and bifunctional scaffolds. We describe the cell sources, biology of seed cells, growth factors, vascular development, and the interactions of relevant molecules. Furthermore, we discuss the challenges and perspectives that may propel the direction of future clinical delivery in bone regeneration.
. [J]. Frontiers of Medicine, 2019, 13(2): 160-188.
Rui Shi, Yuelong Huang, Chi Ma, Chengai Wu, Wei Tian. Current advances for bone regeneration based on tissue engineering strategies. Front. Med., 2019, 13(2): 160-188.
Powder of ceramic, mental, polymer, and their composites
Several in vivo studies have demonstrated its validity and potential in clinical practice
[26, 29−35]
Photosensitivity-based: SLA
Polymers, hydrogels with good photopolymerization capabilities (PPF, gelatin, and TCM-based)
PDLLA composites and PPF/ diethyl fumarate scaffolds were fabricated and cultured with hMSC and MC3T3-E1 osteoblasts
[36–38]
Melt-extrusion-based: FDM
Biodegradable polymers and their composites (PCL, PLGA, PDL, PCL/ tricalcium phosphate, PLGA/TCP/HA)
PCL composite-based scaffolds were fabricated and tested in vitro; PCL/HA bones enhanced the new bone formation in long load-bearing goat femur bone segmental defect model
Increase of osteogenic markers in osteoinductive medium and new bone formation in vivo
[195]
PTH
MC3T3-E1
Increased hydrazine-bisphosphonates affinity to bone and improved hydrazine bisphosphonates interaction with osteoblastic cells in basal medium
[196]
Heparin-binding peptide
Human mesenchymal cells
Increase of mineralization in osteoinductive medium
[197]
Tab.3
Small molecule
Drug delivery system
In vitro/in vivo osteogenesis
References
Phenamil
2D/3D scaffold
Enhanced proliferation of MC3T3 cells, increased ALP expression and enhanced mineralization
[202]
Oxysterols
Hydrogel/sponge/3D scaffold
Oxysterol-21 promoted bone formation in the callus and increased mechanical stability of lumber vertebral segments
[216]
Purmorphamine
Bone adhesive composite beads
Activation of Hh pathway
[222]
FTY720
Bone autografts/ 3D scaffold
Coated allografts promoted new bone formation with significant increases in mechanical properties when compared to the controls
[221]
Simvastatin
3D scaffold/porous bone Cement/ hydrogel
New bone formation was observed after scaffold implantation in tibial defect model. In vivo osteogenesis were observed when loaded scaffolds were combined with MSCs cell sheet
[223,224]
TH (helioxanthin derivative)
Tetrapod-shaped granules
Promote osteoblastic differentiation in mouse MC3T3-E1 cells
[225]
FK506
3D scaffold
Evidenced by the ectopic bone formation in subcutaneous location
[226]
Tab.4
Gene of interest
Delivery system
Cell/animal model
Function
References
Gucocorticoid receptor (GR)
Polymer
Human bone marrow
Successful siRNA delivery and release for up to 40 days
[228]
RANK
Polymer
Murine osteoclast precursor cells
Inhibition of bone resorption due to RANK expression knockdown
ND’souza, F Rossignoli, GGolinelli, GGrisendi, CSpano, OCandini, SOsturu, FCatani, PPaolucci, EMHorwitz, MDominici. Mesenchymal stem/stromal cells as a delivery platform in cell and gene therapies. BMC Med 2015; 13(1): 186 https://doi.org/10.1186/s12916-015-0426-0
pmid: 26265166
7
MFPittenger. Mesenchymal stem cells from adult bone marrow. Methods Mol Biol 2008; 449: 27–44
pmid: 18370081
8
ZGWang, Y Wang, YHuang, QLu, L Zheng, DHu, WKFeng, YLLiu, KT Ji, HYZhang, XBFu, XK Li, MPChu, JXiao. bFGF regulates autophagy and ubiquitinated protein accumulation induced by myocardial ischemia/reperfusion via the activation of the PI3K/Akt/mTOR pathway. Sci Rep 2015; 5(1): 9287 https://doi.org/10.1038/srep09287
pmid: 25787015
LPolo-Corrales, M Latorre-Esteves, JERamirez-Vick. Scaffold design for bone regeneration. J Nanosci Nanotechnol 2014; 14(1): 15–56 https://doi.org/10.1166/jnn.2014.9127
pmid: 24730250
11
JRPorter, TT Ruckh, KCPopat. Bone tissue engineering: a review in bone biomimetics and drug delivery strategies. Biotechnol Prog 2009; 25(6): 1539–1560
pmid: 19824042
DTang, RS Tare, LYYang, DFWilliams, KLOu, RO Oreffo. Biofabrication of bone tissue: approaches, challenges and translation for bone regeneration. Biomaterials 2016; 83: 363–382 https://doi.org/10.1016/j.biomaterials.2016.01.024
pmid: 26803405
14
GMHarris, K Rutledge, QCheng, JBlanchette, EJabbarzadeh. Strategies to direct angiogenesis within scaffolds for bone tissue engineering. Curr Pharm Des 2013; 19(19): 3456–3465 https://doi.org/10.2174/1381612811319190011
pmid: 23432671
15
MAFernandez-Yague, SAAbbah, LMcNamara, DIZeugolis, APandit, MJBiggs. Biomimetic approaches in bone tissue engineering: Integrating biological and physicomechanical strategies. Adv Drug Deliv Rev 2015; 84: 1–29 https://doi.org/10.1016/j.addr.2014.09.005
pmid: 25236302
16
YLi, TT Thula, SJee, SLPerkins, CAparicio, EPDouglas, LBGower. Biomimetic mineralization of woven bone-like nanocomposites: role of collagen cross-links. Biomacromolecules 2012; 13(1): 49–59 https://doi.org/10.1021/bm201070g
pmid: 22133238
17
JVenkatesan, SK Kim. Nano-hydroxyapatite composite biomaterials for bone tissue engineering—a review. J Biomed Nanotechnol 2014; 10(10): 3124–3140 https://doi.org/10.1166/jbn.2014.1893
pmid: 25992432
18
LSang, J Huang, DLuo, ZChen, X Li. Bone-like nanocomposites based on self-assembled protein-based matrices with Ca2+ capturing capability. J Mater Sci Mater Med 2010; 21(9): 2561–2568 https://doi.org/10.1007/s10856-010-4117-2
pmid: 20582716
SPatra, V Young. A review of 3D printing techniques and the future in biofabrication of bioprinted tissue. Cell Biochem Biophys 2016; 74(2): 93–98 https://doi.org/10.1007/s12013-016-0730-0
pmid: 27193609
24
GBrunello, S Sivolella, RMeneghello, LFerroni, CGardin, APiattelli, BZavan, EBressan. Powder-based 3D printing for bone tissue engineering. Biotechnol Adv 2016; 34(5): 740–753 https://doi.org/10.1016/j.biotechadv.2016.03.009
pmid: 27086202
25
PHWarnke, H Seitz, FWarnke, STBecker, SSivananthan, ESherry, QLiu, J Wiltfang, TDouglas. Ceramic scaffolds produced by computer-assisted 3D printing and sintering: characterization and biocompatibility investigations. J Biomed Mater Res B Appl Biomater 2010; 93(1): 212–217
pmid: 20091914
26
YXia, P Zhou, XCheng, YXie, C Liang, CLi, SXu. Selective laser sintering fabrication of nano-hydroxyapatite/poly-e-caprolactone scaffolds for bone tissue engineering applications. Int J Nanomedicine 2013; 8: 4197–4213
pmid: 24204147
CMota, D Puppi, FChiellini, EChiellini. Additive manufacturing techniques for the production of tissue engineering constructs. J Tissue Eng Regen Med 2015; 9(3): 174–190 https://doi.org/10.1002/term.1635
pmid: 23172792
29
LCZhang, H Attar, MCalin, JEckert. Review on manufacture by selective laser melting and properties of titanium based materials for biomedical applications. Mater Technol 2016; 31(2): 66-76 https://doi.org/10.1179/1753555715Y.0000000076
30
CKörner. Additive manufacturing of metallic components by selective electron beam melting—a review. Int Mater Rev 2016; 61(5): 361–367 https://doi.org/10.1080/09506608.2016.1176289
31
SBose, S Tarafder, ABandyopadhyay. Effect of chemistry on osteogenesis and angiogenesis towards bone tissue engineering using 3D printed scaffolds. Ann Biomed Eng 2017; 45(1): 261–272
pmid: 27287311
32
JTorres, F Tamimi, MHAlkhraisat, JCPrados-Frutos, ERastikerdar, UGbureck, JEBarralet, ELópez-Cabarcos. Vertical bone augmentation with 3D-synthetic monetite blocks in the rabbit calvaria. J Clin Periodontol 2011; 38(12): 1147–1153 https://doi.org/10.1111/j.1600-051X.2011.01787.x
pmid: 22092695
33
STarafder, NM Davies, ABandyopadhyay, SBose. 3D printed tricalcium phosphate scaffolds: effect of SrO and MgO doping on in vivo osteogenesis in a rat distal femoral defect model. Biomater Sci 2013; 1(12): 1250–1259 https://doi.org/10.1039/c3bm60132c
pmid: 24729867
34
FTamimi, J Torres, KAl-Abedalla, ELopez-Cabarcos, MHAlkhraisat, DCBassett, UGbureck, JEBarralet. Osseointegration of dental implants in 3D-printed synthetic onlay grafts customized according to bone metabolic activity in recipient site. Biomaterials 2014; 35(21): 5436–5445 https://doi.org/10.1016/j.biomaterials.2014.03.050
pmid: 24726538
35
MCastilho, M Dias, EVorndran, UGbureck, PFernandes, IPires, BGouveia, HArmés, EPires, JRodrigues. Application of a 3D printed customized implant for canine cruciate ligament treatment by tibial tuberosity advancement. Biofabrication 2014; 6(2): 025005 https://doi.org/10.1088/1758-5082/6/2/025005
pmid: 24658159
36
ARonca, L Ambrosio, DWGrijpma. Design of porous three-dimensional PDLLA/nano-hap composite scaffolds using stereolithography. J Appl Biomater Funct Mater 2012; 10(3): 249–258 https://doi.org/10.5301/JABFM.2012.10211
pmid: 23242874
37
PXLan, JW Lee, YJSeol, DWCho. Development of 3D PPF/DEF scaffolds using micro-stereolithography and surface modification. J Mater Sci Mater Med 2009; 20(1): 271–279 https://doi.org/10.1007/s10856-008-3567-2
pmid: 18763023
38
RGuo, S Lu, JMPage, ARMerkel, SBasu, JA Sterling, SAGuelcher. Fabrication of 3D scaffolds with precisely controlled substrate modulus and pore size by templated-fused deposition modeling to direct osteogenic differentiation. Adv Healthc Mater 2015; 4(12): 1826–1832 https://doi.org/10.1002/adhm.201500099
pmid: 26121662
BOstrowska, A Di Luca, KSzlazak, LMoroni, WSwieszkowski. Influence of internal pore architecture on biological and mechanical properties of three-dimensional fiber deposited scaffolds for bone regeneration. J Biomed Mater Res A 2016; 104(4): 991–1001 https://doi.org/10.1002/jbm.a.35637
pmid: 26749200
41
NXu, X Ye, DWei, JZhong, YChen, G Xu, DHe. 3D artificial bones for bone repair prepared by computed tomography-guided fused deposition modeling for bone repair. ACS Appl Mater Interfaces 2014; 6(17): 14952–14963 https://doi.org/10.1021/am502716t
pmid: 25133309
42
YXuan, H Tang, BWu, XDing, Z Lu, WLi, ZXu. A specific groove design for individualized healing in a canine partial sternal defect model by a polycaprolactone/hydroxyapatite scaffold coated with bone marrow stromal cells. J Biomed Mater Res A 2014; 102(10): 3401–3408 https://doi.org/10.1002/jbm.a.35012
pmid: 24142768
43
MMehta, K Schmidt-Bleek, GNDuda, DJMooney. Biomaterial delivery of morphogens to mimic the natural healing cascade in bone. Adv Drug Deliv Rev 2012; 64(12): 1257–1276 https://doi.org/10.1016/j.addr.2012.05.006
pmid: 22626978
44
MFarokhi, F Mottaghitalab, MAShokrgozar, KLOu, C Mao, HHosseinkhani. Importance of dual delivery systems for bone tissue engineering. J Control Release 2016; 225: 152–169 https://doi.org/10.1016/j.jconrel.2016.01.033
pmid: 26805518
45
TMMcFadden, GP Duffy, ABAllen, HYStevens, SMSchwarzmaier, NPlesnila, JMMurphy, FPBarry, REGuldberg, FJO’Brien. The delayed addition of human mesenchymal stem cells to pre-formed endothelial cell networks results in functional vascularization of a collagen-glycosaminoglycan scaffold in vivo. Acta Biomater 2013; 9(12): 9303–9316 https://doi.org/10.1016/j.actbio.2013.08.014
pmid: 23958783
46
EABayer, R Gottardi, MVFedorchak, SRLittle. The scope and sequence of growth factor delivery for vascularized bone tissue regeneration. J Control Release 2015; 219: 129–140 https://doi.org/10.1016/j.jconrel.2015.08.004
pmid: 26264834
SKim, Y Kang, CAKrueger, MSen, JB Holcomb, DChen, JCWenke, YYang. Sequential delivery of BMP-2 and IGF-1 using a chitosan gel with gelatin microspheres enhances early osteoblastic differentiation. Acta Biomater 2012; 8(5): 1768–1777 https://doi.org/10.1016/j.actbio.2012.01.009
pmid: 22293583
49
SNRothstein, KD Huber, NSluis-Cremer, SRLittle. In vitro characterization of a sustained-release formulation for enfuvirtide. Antimicrob Agents Chemother 2014; 58(3): 1797–1799 https://doi.org/10.1128/AAC.02440-13
pmid: 24366751
DHKempen, L Lu, AHeijink, TEHefferan, LBCreemers, AMaran, MJYaszemski, WJDhert. Effect of local sequential VEGF and BMP-2 delivery on ectopic and orthotopic bone regeneration. Biomaterials 2009; 30(14): 2816–2825 https://doi.org/10.1016/j.biomaterials.2009.01.031
pmid: 19232714
52
CWu, W Fan, MGelinsky, YXiao, J Chang, TFriis, GCuniberti. In situ preparation and protein delivery of silicate-alginate composite microspheres with core-shell structure. J R Soc Interface 2011; 8(65): 1804–1814 https://doi.org/10.1098/rsif.2011.0201
pmid: 21613289
53
YBai, Y Leng, GYin, XPu, Z Huang, XLiao, XChen, Y Yao. Effects of combinations of BMP-2 with FGF-2 and/or VEGF on HUVECs angiogenesis in vitro and CAM angiogenesis in vivo. Cell Tissue Res 2014; 356(1): 109–121 https://doi.org/10.1007/s00441-013-1781-9
pmid: 24442492
JLi, M Chen, XFan, HZhou. Recent advances in bioprinting techniques: approaches, applications and future prospects. J Transl Med 2016; 14(1): 271 https://doi.org/10.1186/s12967-016-1028-0
pmid: 27645770
62
HWKang, SJ Lee, IKKo, CKengla, JJYoo, A Atala. A 3D bioprinting system to produce human-scale tissue constructs with structural integrity. Nat Biotechnol 2016; 34(3): 312–319 https://doi.org/10.1038/nbt.3413
pmid: 26878319
XCui, K Breitenkamp, MGFinn, MLotz, DD D’Lima. Direct human cartilage repair using three-dimensional bioprinting technology. Tissue Eng Part A 2012; 18(11-12): 1304–1312 https://doi.org/10.1089/ten.tea.2011.0543
pmid: 22394017
65
XCui, K Breitenkamp, MLotz, DD’Lima. Synergistic action of fibroblast growth factor-2 and transforming growth factor-β1 enhances bioprinted human neocartilage formation. Biotechnol Bioeng 2012; 109(9): 2357–2368 https://doi.org/10.1002/bit.24488
pmid: 22508498
66
XCui, G Gao, YQiu. Accelerated myotube formation using bioprinting technology for biosensor applications. Biotechnol Lett 2013; 35(3): 315–321 https://doi.org/10.1007/s10529-012-1087-0
pmid: 23160742
67
GGao, AF Schilling, TYonezawa, JWang, G Dai, XCui. Bioactive nanoparticles stimulate bone tissue formation in bioprinted three-dimensional scaffold and human mesenchymal stem cells. Biotechnol J 2014; 9(10): 1304–1311 https://doi.org/10.1002/biot.201400305
pmid: 25130390
68
GGao, T Yonezawa, KHubbell, GDai, X Cui. Inkjet-bioprinted acrylated peptides and PEG hydrogel with human mesenchymal stem cells promote robust bone and cartilage formation with minimal printhead clogging. Biotechnol J 2015; 10(10): 1568–1577 https://doi.org/10.1002/biot.201400635
pmid: 25641582
69
GGao, AF Schilling, KHubbell, TYonezawa, DTruong, YHong, G Dai, XCui. Improved properties of bone and cartilage tissue from 3D inkjet-bioprinted human mesenchymal stem cells by simultaneous deposition and photocrosslinking in PEG-GelMA. Biotechnol Lett 2015; 37(11): 2349–2355 https://doi.org/10.1007/s10529-015-1921-2
pmid: 26198849
SCatros, JC Fricain, BGuillotin, BPippenger, RBareille, MRemy, E Lebraud, BDesbat, JAmédée, FGuillemot. Laser-assisted bioprinting for creating on-demand patterns of human osteoprogenitor cells and nano-hydroxyapatite. Biofabrication 2011; 3(2): 025001 https://doi.org/10.1088/1758-5082/3/2/025001
pmid: 21527813
78
MAli, E Pages, ADucom, AFontaine, FGuillemot. Controlling laser-induced jet formation for bioprinting mesenchymal stem cells with high viability and high resolution. Biofabrication 2014; 6(4): 045001 https://doi.org/10.1088/1758-5082/6/4/045001
pmid: 25215452
79
QYao, B Wei, YGuo, CJin, X Du, CYan, JYan, W Hu, YXu, ZZhou, Y Wang, LWang. Design, construction and mechanical testing of digital 3D anatomical data-based PCL-HA bone tissue engineering scaffold. J Mater Sci Mater Med 2015; 26(1): 51 https://doi.org/10.1007/s10856-014-5360-8
pmid: 25596860
80
FPati, TH Song, GRijal, JJang, SW Kim, DWCho. Ornamenting 3D printed scaffolds with cell-laid extracellular matrix for bone tissue regeneration. Biomaterials 2015; 37: 230–241 https://doi.org/10.1016/j.biomaterials.2014.10.012
pmid: 25453953
81
JDBaranski, RR Chaturvedi, KRStevens, JEyckmans, BCarvalho, RDSolorzano, MTYang, JSMiller, SNBhatia, CSChen. Geometric control of vascular networks to enhance engineered tissue integration and function. Proc Natl Acad Sci U S A 2013; 110(19): 7586–7591 https://doi.org/10.1073/pnas.1217796110
pmid: 23610423
MNikkhah, N Eshak, PZorlutuna, NAnnabi, MCastello, KKim, A Dolatshahi-Pirouz, FEdalat, HBae, Y Yang, AKhademhosseini. Directed endothelial cell morphogenesis in micropatterned gelatin methacrylate hydrogels. Biomaterials 2012; 33(35): 9009–9018 https://doi.org/10.1016/j.biomaterials.2012.08.068
pmid: 23018132
85
SRaghavan, CM Nelson, JDBaranski, ELim, CS Chen. Geometrically controlled endothelial tubulogenesis in micropatterned gels. Tissue Eng Part A 2010; 16(7): 2255–2263 https://doi.org/10.1089/ten.tea.2009.0584
pmid: 20180698
86
YZheng, J Chen, MCraven, NWChoi, STotorica, ADiaz-Santana, PKermani, BHempstead, CFischbach-Teschl, JALópez, ADStroock. In vitro microvessels for the study of angiogenesis and thrombosis. Proc Natl Acad Sci U S A 2012; 109(24): 9342–9347 https://doi.org/10.1073/pnas.1201240109
pmid: 22645376
87
LSWray, K Tsioris, ESGi, FGOmenetto, DLKaplan. Slowly degradable porous silk microfabricated scaffolds for vascularized tissue formation. Adv Funct Mater 2013; 23(27): 3404–3412 https://doi.org/10.1002/adfm.201202926
pmid: 24058328
88
JSMiller, KR Stevens, MTYang, BMBaker, DHNguyen, DMCohen, EToro, AA Chen, PAGalie, XYu, R Chaturvedi, SNBhatia, CSChen. Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues. Nat Mater 2012; 11(9): 768–774 https://doi.org/10.1038/nmat3357
pmid: 22751181
ISKinstlinger, DR Yalacki, JSMiller. Engineered tissues with perfusable vascular networks created by sacrificial templating of laser sintered carbohydrates. Front Bioeng Biotechnol 2016; Conference Abstract: 10th World Biomaterials Congress.
91
DBKolesky, RL Truby, ASGladman, TABusbee, KAHoman, JALewis. 3D bioprinting of vascularized, heterogeneous cell-laden tissue constructs. Adv Mater 2014; 26(19): 3124–3130 https://doi.org/10.1002/adma.201305506
pmid: 24550124
92
CLRadtke, R Nino-Fong, BPEsparza Gonzalez, HStryhn, LAMcDuffee. Characterization and osteogenic potential of equine muscle tissue- and periosteal tissue-derived mesenchymal stem cells in comparison with bone marrow- and adipose tissue-derived mesenchymal stem cells. Am J Vet Res 2013; 74(5): 790–800 https://doi.org/10.2460/ajvr.74.5.790
pmid: 23627394
93
SKern, H Eichler, JStoeve, HKlüter, KBieback. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 2006; 24(5): 1294–1301 https://doi.org/10.1634/stemcells.2005-0342
pmid: 16410387
94
APantalone, I Antonucci, MGuelfi, PPantalone, FGUsuelli, LStuppia, VSalini. Amniotic fluid stem cells: an ideal resource for therapeutic application in bone tissue engineering. Eur Rev Med Pharmacol Sci 2016; 20(13): 2884–2890
pmid: 27424990
95
XPetridis, E Diamanti, GChTrigas, DKalyvas, EKitraki. Bone regeneration in critical-size calvarial defects using human dental pulp cells in an extracellular matrix-based scaffold. J Craniomaxillofac Surg 2015; 43(4): 483–490 https://doi.org/10.1016/j.jcms.2015.02.003
pmid: 25753474
96
JGuan, J Zhang, HLi, ZZhu, S Guo, XNiu, YWang, C Zhang. Human urine derived stem cells in combination with b-TCP can be applied for bone regeneration. PLoS One 2015; 10(5): e0125253 https://doi.org/10.1371/journal.pone.0125253
pmid: 25970295
97
DJIllich, N Demir, MStojkovic, MScheer, DRothamel, JNeugebauer, JHescheler, JEZoller. Induced pluripotent stem (iPS) cells and lineage reprogramming: prospects for bone regeneration. Stem Cells 2011; 29(4): 555–563 https://doi.org/10.1002/stem.611
pmid: 21308867
98
CKChan, EY Seo, JYChen, DLo, A McArdle, RSinha, RTevlin, JSeita, JVincent-Tompkins, TWearda, WJLu, K Senarath-Yapa, MTChung, OMarecic, MTran, KS Yan, RUpton, GGWalmsley, ASLee, D Sahoo, CJKuo, ILWeissman, MTLongaker. Identification and specification of the mouse skeletal stem cell. Cell 2015; 160(1-2): 285–298 https://doi.org/10.1016/j.cell.2014.12.002
pmid: 25594184
99
WKAicher, HJ Bühring, MHart, BRolauffs, ABadke, GKlein. Regeneration of cartilage and bone by defined subsets of mesenchymal stromal cells—potential and pitfalls. Adv Drug Deliv Rev 2011; 63(4-5): 342–351 https://doi.org/10.1016/j.addr.2010.12.004
pmid: 21184789
100
OSBeane, VC Fonseca, LLCooper, GKoren, EMDarling. Impact of aging on the regenerative properties of bone marrow-, muscle-, and adipose-derived mesenchymal stem/stromal cells. PLoS One 2014; 9(12): e115963 https://doi.org/10.1371/journal.pone.0115963
pmid: 25541697
101
YYLi, HW Cheng, KMCheung, DChan, BP Chan. Mesenchymal stem cell-collagen microspheres for articular cartilage repair: cell density and differentiation status. Acta Biomater 2014; 10(5): 1919–1929 https://doi.org/10.1016/j.actbio.2014.01.002
pmid: 24418436
102
HMizuno. Adipose-derived stem cells for tissue repair and regeneration: ten years of research and a literature review. J Nippon Med Sch 2009; 76(2): 56–66 https://doi.org/10.1272/jnms.76.56
pmid: 19443990
CFMarkarian, GZ Frey, MDSilveira, EMChem, ARMilani, PBEly, AP Horn, NBNardi, MCamassola. Isolation of adipose-derived stem cells: a comparison among different methods. Biotechnol Lett 2014; 36(4): 693–702 https://doi.org/10.1007/s10529-013-1425-x
pmid: 24322777
105
PCBaer, H Geiger. Adipose-derived mesenchymal stromal/stem cells: tissue localization, characterization, and heterogeneity. Stem Cells Int 2012; 2012: 81
BGharaibeh, A Lu, JTebbets, BZheng, JFeduska, MCrisan, BPéault, JCummins, JHuard. Isolation of a slowly adhering cell fraction containing stem cells from murine skeletal muscle by the preplate technique. Nat Protoc 2008; 3(9): 1501–1509 https://doi.org/10.1038/nprot.2008.142
pmid: 18772878
108
XWu, S Wang, BChen, XAn. Muscle-derived stem cells: isolation, characterization, differentiation, and application in cell and gene therapy. Cell Tissue Res 2010; 340(3): 549–567 https://doi.org/10.1007/s00441-010-0978-4
pmid: 20495827
109
ANimura, T Muneta, HKoga, TMochizuki, KSuzuki, HMakino, AUmezawa, ISekiya. Increased proliferation of human synovial mesenchymal stem cells with autologous human serum: comparisons with bone marrow mesenchymal stem cells and with fetal bovine serum. Arthritis Rheum 2008; 58(2): 501–510 https://doi.org/10.1002/art.23219
pmid: 18240254
110
JFan, RR Varshney, LRen, DCai, DA Wang. Synovium-derived mesenchymal stem cells: a new cell source for musculoskeletal regeneration. Tissue Eng Part B Rev 2009; 15(1): 75–86 https://doi.org/10.1089/ten.teb.2008.0586
pmid: 19196118
JJGuan, X Niu, FXGong, BHu, SC Guo, YLLou, CQZhang, ZFDeng, YWang. Biological characteristics of human-urine-derived stem cells: potential for cell-based therapy in neurology. Tissue Eng Part A 2014; 20(13-14): 1794–1806 https://doi.org/10.1089/ten.tea.2013.0584
pmid: 24387670
YSHwang, JM Polak, AMantalaris. In vitro direct osteogenesis of murine embryonic stem cells without embryoid body formation. Stem Cells Dev 2008; 17(5): 963–970 https://doi.org/10.1089/scd.2007.0228
pmid: 18564030
115
SStröm, J Inzunza, KHGrinnemo, KHolmberg, EMatilainen, AMStrömberg, EBlennow, OHovatta. Mechanical isolation of the inner cell mass is effective in derivation of new human embryonic stem cell lines. Hum Reprod 2007; 22(12): 3051–3058 https://doi.org/10.1093/humrep/dem335
pmid: 17959612
CYFong, LL Chak, ABiswas, JHTan, K Gauthaman, WKChan, ABongso. Human Wharton’s jelly stem cells have unique transcriptome profiles compared to human embryonic stem cells and other mesenchymal stem cells. Stem Cell Rev 2011; 7(1): 1–16 https://doi.org/10.1007/s12015-010-9166-x
pmid: 20602182
118
PHuang, LM Lin, XYWu, QLTang, XYFeng, GYLin, X Lin, HWWang, THHuang, LMa. Differentiation of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells into germ-like cells in vitro. J Cell Biochem 2010; 109(4): 747–754
pmid: 20052672
119
PDe Coppi, G Bartsch Jr, MMSiddiqui, TXu, CC Santos, LPerin, GMostoslavsky, ACSerre, EYSnyder, JJYoo, ME Furth, SSoker, AAtala. Isolation of amniotic stem cell lines with potential for therapy. Nat Biotechnol 2007; 25(1): 100–106 https://doi.org/10.1038/nbt1274
pmid: 17206138
120
MGRoubelakis, KI Pappa, VBitsika, DZagoura, AVlahou, HAPapadaki, AAntsaklis, NPAnagnou. Molecular and proteomic characterization of human mesenchymal stem cells derived from amniotic fluid: comparison to bone marrow mesenchymal stem cells. Stem Cells Dev 2007; 16(6): 931–952 https://doi.org/10.1089/scd.2007.0036
pmid: 18047393
121
OTrohatou, NP Anagnou, MGRoubelakis. Human amniotic fluid stem cells as an attractive tool for clinical applications. Curr Stem Cell Res Ther 2013; 8(2): 125–132 https://doi.org/10.2174/1574888X11308020003
pmid: 23140502
122
SGholizadeh-Ghaleh Aziz, FPashaei-Asl, ZFardyazar, MPashaiasl. Isolation, characterization, cryopreservation of human amniotic stem cells and differentiation to osteogenic and adipogenic cells. PLoS One 2016; 11(7): e0158281
pmid: 27434028
123
JMLee, J Jung, HJLee, SJJeong, KJCho, SG Hwang, GJKim. Comparison of immunomodulatory effects of placenta mesenchymal stem cells with bone marrow and adipose mesenchymal stem cells. Int Immunopharmacol 2012; 13(2): 219–224 https://doi.org/10.1016/j.intimp.2012.03.024
pmid: 22487126
124
HFazekasova, R Lechler, KLangford, GLombardi. Placenta-derived MSCs are partially immunogenic and less immunomodulatory than bone marrow-derived MSCs. J Tissue Eng Regen Med 2011; 5(9): 684–694 https://doi.org/10.1002/term.362
pmid: 21953866
125
ZNZhong, SF Zhu, ADYuan, GHLu, ZY He, ZQFa, WHLi. Potential of placenta-derived mesenchymal stem cells as seed cells for bone tissue engineering: preliminary study of osteoblastic differentiation and immunogenicity. Orthopedics 2012; 35(9): 779–788 https://doi.org/10.3928/01477447-20120822-07
pmid: 22955387
126
OVSemenov, S Koestenbauer, MRiegel, NZech, R Zimmermann, AHZisch, AMalek. Multipotent mesenchymal stem cells from human placenta: critical parameters for isolation and maintenance of stemness after isolation. Am J Obstet Gynecol 2010; 202(2): 193.e1–193.e13 https://doi.org/10.1016/j.ajog.2009.10.869
pmid: 20035913
127
ALange-Consiglio, B Corradetti, AMeucci, RPerego, DBizzaro, FCremonesi. Characteristics of equine mesenchymal stem cells derived from amnion and bone marrow: in vitro proliferative and multilineage potential assessment. Equine Vet J 2013; 45(6): 737–744 https://doi.org/10.1111/evj.12052
pmid: 23527626
128
SViolini, C Gorni, LFPisani, PRamelli, MCaniatti, PMariani. Isolation and differentiation potential of an equine amnion-derived stromal cell line. Cytotechnology 2012; 64(1): 1–7 https://doi.org/10.1007/s10616-011-9398-x
pmid: 21994048
129
KTakahashi, S Yamanaka. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126(4): 663–676 https://doi.org/10.1016/j.cell.2006.07.024
pmid: 16904174
130
KTakahashi, K Tanabe, MOhnuki, MNarita, TIchisaka, KTomoda, SYamanaka. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007; 131(5): 861–872 https://doi.org/10.1016/j.cell.2007.11.019
pmid: 18035408
131
JYu, MA Vodyanik, KSmuga-Otto, JAntosiewicz-Bourget, JLFrane, STian, J Nie, GAJonsdottir, VRuotti, RStewart, IISlukvin, JAThomson. Induced pluripotent stem cell lines derived from human somatic cells. Science 2007; 318(5858): 1917–1920 https://doi.org/10.1126/science.1151526
pmid: 18029452
MGrellier, L Bordenave, JAmédée. Cell-to-cell communication between osteogenic and endothelial lineages: implications for tissue engineering. Trends Biotechnol 2009; 27(10): 562–571 https://doi.org/10.1016/j.tibtech.2009.07.001
pmid: 19683818
134
TNakasa, O Ishida, TSunagawa, ANakamae, YYasunaga, MAgung, MOchi. Prefabrication of vascularized bone graft using a combination of fibroblast growth factor-2 and vascular bundle implantation into a novel interconnected porous calcium hydroxyapatite ceramic. J Biomed Mater Res A 2005; 75(2): 350–355 https://doi.org/10.1002/jbm.a.30435
pmid: 16088890
135
KKawamura, H Yajima, HOhgushi, YTomita, YKobata, KShigematsu, YTakakura. Experimental study of vascularized tissue-engineered bone grafts. Plast Reconstr Surg 2006; 117(5): 1471–1479 https://doi.org/10.1097/01.prs.0000197883.17428.22
pmid: 16641715
136
HSun, Z Qu, YGuo, GZang, B Yang. In vitro and in vivo effects of rat kidney vascular endothelial cells on osteogenesis of rat bone marrow mesenchymal stem cells growing on polylactide-glycoli acid (PLGA) scaffolds. Biomed Eng Online 2007; 6: 41
pmid: 17980048
137
YXue, Z Xing, AIBolstad, TEVan Dyke, KMustafa. Co-culture of human bone marrow stromal cells with endothelial cells alters gene expression profiles. Int J Artif Organs 2013; 36(9): 650–662 https://doi.org/10.5301/ijao.5000229
pmid: 23918270
AStahl, A Wenger, HWeber, GBStark, HGAugustin, GFinkenzeller. Bi-directional cell contact-dependent regulation of gene expression between endothelial cells and osteoblasts in a three-dimensional spheroidal coculture model. Biochem Biophys Res Commun 2004; 322(2): 684–692 https://doi.org/10.1016/j.bbrc.2004.07.175
pmid: 15325284
140
MISantos, RE Unger, RASousa, RLReis, CJKirkpatrick. Crosstalk between osteoblasts and endothelial cells co-cultured on a polycaprolactone-starch scaffold and the in vitro development of vascularization. Biomaterials 2009; 30(26): 4407–4415 https://doi.org/10.1016/j.biomaterials.2009.05.004
pmid: 19487022
141
EDohle, S Fuchs, MKolbe, AHofmann, HSchmidt, CJKirkpatrick. Sonic hedgehog promotes angiogenesis and osteogenesis in a coculture system consisting of primary osteoblasts and outgrowth endothelial cells. Tissue Eng Part A 2010; 16(4): 1235–1237 https://doi.org/10.1089/ten.tea.2009.0493
pmid: 19886747
142
CColnot. Skeletal cell fate decisions within periosteum and bone marrow during bone regeneration. J Bone Miner Res 2009; 24(2): 274–282 https://doi.org/10.1359/jbmr.081003
pmid: 18847330
143
DChen, X Zhang, YHe, JLu, H Shen, YJiang, CZhang, BZeng. Co-culturing mesenchymal stem cells from bone marrow and periosteum enhances osteogenesis and neovascularization of tissue-engineered bone. J Tissue Eng Regen Med 2012; 6(10): 822–832 https://doi.org/10.1002/term.489
pmid: 22072318
144
DChen, H Shen, YHe, YChen, Q Wang, JLu, YJiang. Synergetic effects of hBMSCs and hPCs in osteogenic differentiation and their capacity in the repair of critical-sized femoral condyle defects. Mol Med Rep 2015; 11(2): 1111–1119 https://doi.org/10.3892/mmr.2014.2883
pmid: 25373389
145
JSPark, KH Park. Light enhanced bone regeneration in an athymic nude mouse implanted with mesenchymal stem cells embedded in PLGA microspheres. Biomater Res 2016; 20(1): 4 https://doi.org/10.1186/s40824-016-0051-9
pmid: 26893909
146
LWu, X Zhao, BHe, JJiang, XJXie, L Liu. The possible roles of biological bone constructed with peripheral blood derived EPCs and BMSCs in osteogenesis and angiogenesis. Biomed Res Int. 2016; 2016:8168943
147
JNFisher, GM Peretti, CScotti. Stem cells for bone regeneration: from cell-based therapies to decellularised engineered extracellular matrices. Stem Cells Int 2016; 2016:9352598
148
RIDmitrieva, IR Minullina, AABilibina, OVTarasova, SVAnisimov, AYZaritskey. Bone marrow- and subcutaneous adipose tissue-derived mesenchymal stem cells: differences and similarities. Cell Cycle 2012; 11(2): 377–383 https://doi.org/10.4161/cc.11.2.18858
pmid: 22189711
149
JBrocher, P Janicki, PVoltz, ESeebach, ENeumann, UMueller-Ladner, WRichter. Inferior ectopic bone formation of mesenchymal stromal cells from adipose tissue compared to bone marrow: rescue by chondrogenic pre-induction. Stem Cell Res 2013; 11(3): 1393–1406 https://doi.org/10.1016/j.scr.2013.07.008
pmid: 24140198
150
GKSándor, J Numminen, JWolff, TThesleff, AMiettinen, VJTuovinen, BMannerström, MPatrikoski, RSeppänen, SMiettinen, MRautiainen, JÖhman. Adipose stem cells used to reconstruct 13 cases with cranio-maxillofacial hard-tissue defects. Stem Cells Transl Med 2014; 3(4): 530–540 https://doi.org/10.5966/sctm.2013-0173
pmid: 24558162
151
LTKuhn, Y Liu, NLBoyd, JEDennis, XJiang, XXin, LF Charles, LWang, HLAguila, DWRowe, ACLichtler, AJGoldberg. Developmental-like bone regeneration by human embryonic stem cell-derived mesenchymal cells. Tissue Eng Part A 2014; 20(1-2): 365–377 https://doi.org/10.1089/ten.tea.2013.0321
pmid: 23952622
152
BLevi, JS Hyun, DTMontoro, DDLo, CK Chan, SHu, NSun, M Lee, MGrova, AJConnolly, JCWu, GC Gurtner, ILWeissman, DCWan, MT Longaker. In vivo directed differentiation of pluripotent stem cells for skeletal regeneration. Proc Natl Acad Sci U S A 2012; 109(50): 20379–20384 https://doi.org/10.1073/pnas.1218052109
pmid: 23169671
153
MMathieu, S Rigutto, AIngels, DSpruyt, NStricwant, IKharroubi, VAlbarani, MJayankura, JRasschaert, EBastianelli, VGangji. Decreased pool of mesenchymal stem cells is associated with altered chemokines serum levels in atrophic nonunion fractures. Bone 2013; 53(2): 391–398 https://doi.org/10.1016/j.bone.2013.01.005
pmid: 23318974
154
YYamada, S Nakamura, KIto, TSugito, RYoshimi, TNagasaka, MUeda. A feasibility of useful cell-based therapy by bone regeneration with deciduous tooth stem cells, dental pulp stem cells, or bone-marrow-derived mesenchymal stem cells for clinical study using tissue engineering technology. Tissue Eng Part A 2010; 16(6): 1891–1900 https://doi.org/10.1089/ten.tea.2009.0732
pmid: 20067397
JMassagué, D Wotton. Transcriptional control by the TGF-β/Smad signaling system. EMBO J 2000; 19(8): 1745–1754 PMID:10775259 https://doi.org/10.1093/emboj/19.8.1745
157
MEJoyce, S Jingushi, MEBolander. Transforming growth factor-β in the regulation of fracture repair. Orthop Clin North Am 1990; 21(1): 199–209
pmid: 2296458
MACritchlow, YS Bland, DEAshhurst. The effect of exogenous transforming growth factor-β 2 on healing fractures in the rabbit. Bone 1995; 16(5): 521–527 https://doi.org/10.1016/8756-3282(95)00085-R
pmid: 7654467
160
NTamai, A Myoui, MHirao, TKaito, TOchi, J Tanaka, KTakaoka, HYoshikawa. A new biotechnology for articular cartilage repair: subchondral implantation of a composite of interconnected porous hydroxyapatite, synthetic polymer (PLA-PEG), and bone morphogenetic protein-2 (rhBMP-2). Osteoarthritis Cartilage 2005; 13(5): 405–417 https://doi.org/10.1016/j.joca.2004.12.014
pmid: 15882564
161
KVrijens, W Lin, JCui, DFarmer, JLow, E Pronier, FYZeng, AAShelat, KGuy, MR Taylor, TChen, MFRoussel. Identification of small molecule activators of BMP signaling. PLoS One 2013; 8(3): e59045 https://doi.org/10.1371/journal.pone.0059045
pmid: 23527084
162
ABandyopadhyay, PS Yadav, PPrashar. BMP signaling in development and diseases: a pharmacological perspective. Biochem Pharmacol 2013; 85(7): 857–864 https://doi.org/10.1016/j.bcp.2013.01.004
pmid: 23333766
163
EBergeron, E Leblanc, ODrevelle, RGiguère, SBeauvais, GGrenier, NFaucheux. The evaluation of ectopic bone formation induced by delivery systems for bone morphogenetic protein-9 or its derived peptide. Tissue Eng Part A 2012; 18(3-4): 342–352 https://doi.org/10.1089/ten.tea.2011.0008
pmid: 21902464
164
YTakahashi, M Yamamoto, KYamada, OKawakami, YTabata. Skull bone regeneration in nonhuman primates by controlled release of bone morphogenetic protein-2 from a biodegradable hydrogel. Tissue Eng 2007; 13(2): 293–300 https://doi.org/10.1089/ten.2006.0088
pmid: 17504062
165
PAZuk, M Zhu, PAshjian, DADe Ugarte, JIHuang, HMizuno, ZCAlfonso, JKFraser, PBenhaim, MHHedrick. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 2002; 13(12): 4279–4295 https://doi.org/10.1091/mbc.E02-02-0105
pmid: 12475952
166
JWang, Y Zheng, JZhao, TLiu, L Gao, ZGu, GWu. Low-dose rhBMP2/7 heterodimer to reconstruct peri-implant bone defects: a micro-CT evaluation. J Clin Periodontol 2012; 39(1): 98–105 https://doi.org/10.1111/j.1600-051X.2011.01807.x
pmid: 22092868
167
XHe, Y Liu, XYuan, LLu. Enhanced healing of rat calvarial defects with MSCs loaded on BMP-2 releasing chitosan/alginate/hydroxyapatite scaffolds. PLoS One 2014; 9(8): e104061 https://doi.org/10.1371/journal.pone.0104061
pmid: 25084008
168
JLi, J Hong, QZheng, XGuo, S Lan, FCui, HPan, Z Zou, CChen. Repair of rat cranial bone defects with nHAC/PLLA and BMP-2-related peptide or rhBMP-2. J Orthop Res 2011; 29(11): 1745–1752 https://doi.org/10.1002/jor.21439
pmid: 21500252
169
MLind. Growth factor stimulation of bone healing. Effects on osteoblasts, osteomies, and implants fixation. Acta Orthop Scand Suppl 1998; 283: 2–37
pmid: 9856074
170
TKato, H Kawaguchi, KHanada, LAoyama, YHiyama, TNakamura, KKu-zutani, MTamura, TKurokawa, KNakamura. Single local injection of re-combinant fibroblast growth factor-2 stimulates healing of segmental bone defects in rabbits. J Orthop Res 1998; 16: 654–659 https://doi.org/10.1002/jor.1100160605
pmid: 9877388
171
ZLiu, KJ Lavine, IHHung, DMOrnitz. FGF18 is required for early chondrocyte proliferation, hypertrophy and vascular invasion of the growth plate. Dev Biol 2007; 302(1): 80–91 https://doi.org/10.1016/j.ydbio.2006.08.071
pmid: 17014841
172
GJSchmid, C Kobayashi, LJSandell, DMOrnitz. Fibroblast growth factor expression during skeletal fracture healing in mice. Dev Dyn 2009; 238(3): 766–774 https://doi.org/10.1002/dvdy.21882
pmid: 19235733
173
BBehr, P Leucht, MTLongaker, NQuarto. Fgf-9 is required for angiogenesis and osteogenesis in long bone repair. Proc Natl Acad Sci U S A 2010; 107(26): 11853–11858 https://doi.org/10.1073/pnas.1003317107
pmid: 20547837
SRThaller, A Dart, HTesluk. The effects of insulin-like growth factor-1 on critical-size calvarial defects in Sprague-Dawley rats. Ann Plast Surg 1993; 31(5): 429–433 https://doi.org/10.1097/00000637-199311000-00007
pmid: 8285528
176
CESegar, ME Ogle, EABotchwey. Regulation of angiogenesis and bone regeneration with natural and synthetic small molecules. Curr Pharm Des 2013; 19(19): 3403–3419 https://doi.org/10.2174/1381612811319190007
pmid: 23432670
177
JStreet, M Bao, LdeGuzman, SBunting, FVPeale Jr, NFerrara, HSteinmetz, JHoeffel, JLCleland, ADaugherty, Nvan Bruggen, HPRedmond, RACarano, EHFilvaroff. Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover. Proc Natl Acad Sci U S A 2002; 99(15): 9656–9661 https://doi.org/10.1073/pnas.152324099
pmid: 12118119
178
PJBouletreau, SM Warren, JASpector, ZMPeled, RPGerrets, JAGreenwald, MTLongaker. Hypoxia and VEGF up-regulate BMP-2 mRNA and protein expression in microvascular endothelial cells: implications for fracture healing. Plast Reconstr Surg 2002; 109(7): 2384–2397 https://doi.org/10.1097/00006534-200206000-00033
pmid: 12045566
179
EZelzer, W McLean, YSNg, NFukai, AMReginato, SLovejoy, PAD’Amore, BROlsen. Skeletal defects in VEGF(120/120) mice reveal multiple roles for VEGF in skeletogenesis. Development 2002; 129(8): 1893–1904
pmid: 11934855
180
FCui, X Wang, XLiu, ASDighe, GBalian, QCui. VEGF and BMP-6 enhance bone formation mediated by cloned mouse osteoprogenitor cells. Growth Factors 2010; 28(5): 306–317 https://doi.org/10.3109/08977194.2010.484423
pmid: 20497064
181
IBab, D Gazit, MChorev, AMuhlrad, AShteyer, ZGreenberg, MNamdar, AKahn. Histone H4-related osteogenic growth peptide (OGP): a novel circulating stimulator of osteoblastic activity. EMBO J 1992; 11(5): 1867–1873
pmid: 1582415
182
NGabarin, H Gavish, AMuhlrad, YCChen, MNamdar-Attar, RANissenson, MChorev, IBab. Mitogenic G(i) protein-MAP kinase signaling cascade in MC3T3-E1 osteogenic cells: activation by C-terminal pentapeptide of osteogenic growth peptide [OGP(10-14)] and attenuation of activation by cAMP. J Cell Biochem 2001; 81(4): 594–603 https://doi.org/10.1002/jcb.1083
pmid: 11329614
183
GAn, Z Xue, BZhang, QKDeng, YSWang, SCLv. Expressing osteogenic growth peptide in the rabbit bone mesenchymal stem cells increased alkaline phosphatase activity and enhanced the collagen accumulation. Eur Rev Med Pharmacol Sci 2014; 18(11): 1618–1624
pmid: 24943972
184
MABrager, MJ Patterson, JFConnolly, ZNevo. Osteogenic growth peptide normally stimulated by blood loss and marrow ablation has local and systemic effects on fracture healing in rats. J Orthop Res 2000; 18(1): 133–139 https://doi.org/10.1002/jor.1100180119
pmid: 10716289
185
MShuqiang, W Kunzheng, DXiaoqiang, WWei, Z Mingyu, WDaocheng. Osteogenic growth peptide incorporated into PLGA scaffolds accelerates healing of segmental long bone defects in rabbits. J Plast Reconstr Aesthet Surg 2008; 61(12): 1558–1560 https://doi.org/10.1016/j.bjps.2008.03.040
pmid: 18676213
TManabe, S Mori, TMashiba, YKaji, K Iwata, SKomatsubara, ASeki, YX Sun, TYamamoto. Human parathyroid hormone (1-34) accelerates natural fracture healing process in the femoral osteotomy model of cynomolgus monkeys. Bone 2007; 40(6): 1475–1482 https://doi.org/10.1016/j.bone.2007.01.015
pmid: 17369013
188
DEKomatsu, KA Brune, HLiu, ALSchmidt, BHan, QQ Zeng, XYang, JSNunes, YLu, AG Geiser, YLMa, JAWolos, MSWestmore, MSato. Longitudinal in vivo analysis of the region-specific efficacy of parathyroid hormone in a rat cortical defect model. Endocrinology 2009; 150(4): 1570–1579 https://doi.org/10.1210/en.2008-0814
pmid: 19022894
189
REJung, DL Cochran, ODomken, RSeibl, AAJones, DBuser, CHHammerle. The effect of matrix bound parathyroid hormone on bone regeneration. Clin Oral Implants Res 2007; 18(3): 319–325 https://doi.org/10.1111/j.1600-0501.2007.01342.x
pmid: 17386063
190
LAKaback, Y Soung, ANaik, GGeneau, EMSchwarz, RNRosier, RJO’Keefe, HDrissi. Teriparatide (1-34 human PTH) regulation of osterix during fracture repair. J Cell Biochem 2008; 105(1): 219–226 https://doi.org/10.1002/jcb.21816
pmid: 18494002
191
PAspenberg, HK Genant, TJohansson, AJNino, KSee, K Krohn, PA García-Hernández, CPRecknor, TAEinhorn, GPDalsky, BHMitlak, AFierlinger, MCLakshmanan. Teriparatide for acceleration of fracture repair in humans: a prospective, randomized, double-blind study of 102 postmenopausal women with distal radial fractures. J Bone Miner Res 2010; 25(2): 404–414 https://doi.org/10.1359/jbmr.090731
pmid: 19594305
192
DGReynolds, S Shaikh, MOPapuga, ALLerner, RJO’Keefe, EMSchwarz, HAAwad. muCT-based measurement of cortical bone graft-to-host union. J Bone Miner Res 2009; 24(5): 899–907 https://doi.org/10.1359/jbmr.081232
pmid: 19063685
193
KJManton, DFM Leong, SMCool, VNurcombe. Disruption of heparan and chondroitin sulfate signaling enhances mesenchymal stem cell-derived osteogenic differentiation via bone morphogenetic protein signaling pathways. Stem Cells 2007; 25(11): 2845–2854 https://doi.org/10.1634/stemcells.2007-0065
pmid: 17702986
194
YJChoi, JY Lee, JHPark, JBPark, JSSuh, YS Choi, SJLee, CPChung, YJPark. The identification of a heparin binding domain peptide from bone morphogenetic protein-4 and its role on osteogenesis. Biomaterials 2010; 31(28): 7226–7238 https://doi.org/10.1016/j.biomaterials.2010.05.022
pmid: 20621352
195
JYLee, JE Choo, HJPark, JBPark, SCLee, I Jo, SJLee, CPChung, YJPark. Injectable gel with synthetic collagen-binding peptide for enhanced osteogenesis in vitro and in vivo. Biochem Biophys Res Commun 2007; 357(1): 68–74 https://doi.org/10.1016/j.bbrc.2007.03.106
pmid: 17418806
ARezania, KE Healy. Biomimetic peptide surfaces that regulate adhesion, spreading, cytoskeletal organization, and mineralization of the matrix deposited by osteoblast-like cells. Biotechnol Prog 1999; 15(1): 19–32 https://doi.org/10.1021/bp980083b
pmid: 9933510
198
KWLo, KM Ashe, HMKan, CTLaurencin. The role of small molecules in musculoskeletal regeneration. Regen Med 2012; 7(4): 535–549 https://doi.org/10.2217/rme.12.33
pmid: 22817627
SRuiz-Gaspa, X Nogues, AEnjuanes, JCMonllau, JBlanch, RCarreras, LMellibovsky, DGrinberg, SBalcells, ADíez-Perez, JPedro-Botet. Simvastatin and atorvastatin enhance gene expression of collagen type 1 and osteocalcin in primary human osteoblasts and MG-63 cultures. J Cell Biochem 2007; 101(6): 1430–1438 https://doi.org/10.1002/jcb.21259
pmid: 17252541
201
YMoriyama, Y Ayukawa, YOgino, IAtsuta, MTodo, Y Takao, KKoyano. Local application of fluvastatin improves peri-implant bone quantity and mechanical properties: a rodent study. Acta Biomater 2010; 6(4): 1610–1618 https://doi.org/10.1016/j.actbio.2009.10.045
pmid: 19887121
202
KWLo, BD Ulery, HMKan, KMAshe, CTLaurencin. Evaluating the feasibility of utilizing the small molecule phenamil as a novel biofactor for bone regenerative engineering. J Tissue Eng Regen Med 2014; 8(9): 728–736 https://doi.org/10.1002/term.1573
pmid: 22815259
KWPark, H Waki, WKKim, BSDavies, SGYoung, FParhami, PTontonoz. The small molecule phenamil induces osteoblast differentiation and mineralization. Mol Cell Biol 2009; 29(14): 3905–3914 https://doi.org/10.1128/MCB.00002-09
pmid: 19433444
205
JZhao, S Ohba, MShinkai, UIChung, TNagamune. Icariin induces osteogenic differentiation in vitro in a BMP- and Runx2-dependent manner. Biochem Biophys Res Commun 2008; 369(2): 444–448 https://doi.org/10.1016/j.bbrc.2008.02.054
pmid: 18295595
206
KNakajima, Y Komiyama, HHojo, SOhba, F Yano, NNishikawa, SIhara, HAburatani, TTakato, UIChung. Enhancement of bone formation ex vivo and in vivo by a helioxanthin-derivative. Biochem Biophys Res Commun 2010; 395(4): 502–508 https://doi.org/10.1016/j.bbrc.2010.04.041
pmid: 20382113
XWu, S Ding, QDing, NSGray, PGSchultz. A small molecule with osteogenesis-inducing activity in multipotent mesenchymal progenitor cells. J Am Chem Soc 2002; 124(49): 14520–14521 https://doi.org/10.1021/ja0283908
pmid: 12465946
209
RBCorcoran, MP Scott. Oxysterols stimulate Sonic hedgehog signal transduction and proliferation of medulloblastoma cells. Proc Natl Acad Sci USA 2006; 103(22): 8408–8413 https://doi.org/10.1073/pnas.0602852103
pmid: 16707575
210
AWJames. Review of signaling pathways governing MSC osteogenic and adipogenic differentiation. Scientifica (Cairo) 2013; 2013: 684736
KGellynck, R Shah, MParkar, AYoung, PBuxton, PBrett. Small molecule stimulation enhances bone regeneration but not titanium implant osseointegration. Bone 2013; 57(2): 405–412 https://doi.org/10.1016/j.bone.2013.09.012
pmid: 24076022
213
CMAmantea, WK Kim, VMeliton, STetradis, FParhami. Oxysterol-induced osteogenic differentiation of marrow stromal cells is regulated by Dkk-1 inhibitable and PI3-kinase mediated signaling. J Cell Biochem 2008; 105(2): 424–436 https://doi.org/10.1002/jcb.21840
pmid: 18613030
214
TLAghaloo, CM Amantea, CMCowan, JARichardson, BMWu, F Parhami, STetradis. Oxysterols enhance osteoblast differentiation in vitro and bone healing in vivo. J Orthop Res 2007; 25(11): 1488–1497 https://doi.org/10.1002/jor.20437
pmid: 17568450
215
FStappenbeck, W Xiao, MEpperson, MRiley, APriest, DHuang, KNguyen, MEJung, RSThies, FFarouz. Novel oxysterols activate the Hedgehog pathway and induce osteogenesis. Bioorg Med Chem Lett 2012; 22(18): 5893–5897 https://doi.org/10.1016/j.bmcl.2012.07.073
pmid: 22901899
216
RSiddappa, A Martens, JDoorn, ALeusink, COlivo, RLicht, Lvan Rijn, CGaspar, RFodde, FJanssen, Cvan Blitterswijk, Jde Boer. cAMP/PKA pathway activation in human mesenchymal stem cells in vitro results in robust bone formation in vivo. Proc Natl Acad Sci U S A 2008; 105(20): 7281–7286 https://doi.org/10.1073/pnas.0711190105
pmid: 18490653
217
KWHLo, HM Kan, KMAshe, CTLaurencin. The small molecule PKA-specific cyclic AMP analogue as an inducer of osteoblast-like cells differentiation and mineralization. J Tissue Eng Regen Med 2012; 6(1): 40–48 https://doi.org/10.1002/term.395
pmid: 21312339
218
KWLo, HM Kan, KAGagnon, CTLaurencin. One-day treatment of small molecule 8-bromo-cyclic AMP analogue induces cell-based VEGF production for in vitro angiogenesis and osteoblastic differentiation. J Tissue Eng Regen Med 2016; 10(10): 867–875 https://doi.org/10.1002/term.1839
pmid: 24493289
CEPetrie Aronin, LSSefcik, SSTholpady, ATholpady, KWSadik, TLMacdonald, SMPeirce, BRWamhoff, KRLynch, RCOgle, EABotchwey. FTY720 promotes local microvascular network formation and regeneration of cranial bone defects. Tissue Eng Part A 2010; 16(6): 1801–1809 https://doi.org/10.1089/ten.tea.2009.0539
pmid: 20038198
221
CEPetrie Aronin, SJShin, KBNaden, PDRios Jr, LSSefcik, SRZawodny, NDBagayoko, QCui, Y Khan, EABotchwey. The enhancement of bone allograft incorporation by the local delivery of the sphingosine 1-phosphate receptor targeted drug FTY720. Biomaterials 2010; 31(25): 6417–6424 https://doi.org/10.1016/j.biomaterials.2010.04.061
pmid: 20621764
222
KGellynck, EA Neel, HLi, NMardas, NDonos, PBuxton, AMYoung. Cell attachment and response to photocured, degradable bone adhesives containing tricalcium phosphate and purmorphamine. Acta Biomater 2011; 7(6): 2672–2677 https://doi.org/10.1016/j.actbio.2011.02.033
pmid: 21354477
223
YQi, T Zhao, WYan, KXu, Z Shi, JWang. Mesenchymal stem cell sheet transplantation combined with locally released simvastatin enhances bone formation in a rat tibia osteotomy model. Cytotherapy 2013; 15(1): 44–56 https://doi.org/10.1016/j.jcyt.2012.10.006
pmid: 23260085
224
YMaeda, H Hojo, NShimohata, SChoi, K Yamamoto, TTakato, UIChung, SOhba. Bone healing by sterilizable calcium phosphate tetrapods eluting osteogenic molecules. Biomaterials 2013; 34(22): 5530–5537 https://doi.org/10.1016/j.biomaterials.2013.03.089
pmid: 23623228
225
SOhba, K Nakajima, YKomiyama, FKugimiya, KIgawa, KItaka, TMoro, K Nakamura, HKawaguchi, TTakato, UIChung. A novel osteogenic helioxanthin-derivative acts in a BMP-dependent manner. Biochem Biophys Res Commun 2007; 357(4): 854–860 https://doi.org/10.1016/j.bbrc.2007.03.173
pmid: 17451649
226
AChatterjea, VL LaPointe, JAlblas, SChatterjea, CAvan Blitterswijk, Jde Boer. Suppression of the immune system as a critical step for bone formation from allogeneic osteoprogenitors implanted in rats. J Cell Mol Med 2014; 18(1): 134–142 https://doi.org/10.1111/jcmm.12172
pmid: 24237965
227
SGhadakzadeh, M Mekhail, AAoude, RHamdy, MTabrizian. Small players ruling the hard game: siRNA in bone regeneration. J Bone Miner Res 2016; 31(3): 475–487 https://doi.org/10.1002/jbmr.2816
pmid: 26890411
228
LHong, N Wei, VJoshi, YYu, N Kim, YKrishnamachari, QZhang, AKSalem. Effects of glucocorticoid receptor small interfering RNA delivered using poly lactic-co-glycolic acid microparticles on proliferation and differentiation capabilities of human mesenchymal stromal cells. Tissue Eng Part A 2012; 18(7-8): 775–784 https://doi.org/10.1089/ten.tea.2011.0432
pmid: 21988716
229
YWang, KK Tran, HShen, DWGrainger. Selective local delivery of RANK siRNA to bone phagocytes using bone augmentation biomaterials. Biomaterials 2012; 33(33): 8540–8547 https://doi.org/10.1016/j.biomaterials.2012.07.039
pmid: 22951320
230
YZhang, L Wei, RJMiron, BShi, Z Bian. Anabolic bone formation via a site-specific bone-targeting delivery system by interfering with semaphorin 4D expression. J Bone Miner Res 2015; 30(2): 286–296 https://doi.org/10.1002/jbmr.2322
pmid: 25088728
231
YZhang, L Wei, RJMiron, QZhang, ZBian. Prevention of alveolar bone loss in an osteoporotic animal model via interference of semaphorin 4d. J Dent Res 2014; 93(11): 1095–1100 https://doi.org/10.1177/0022034514552676
pmid: 25252878
232
ALJackson, PS Linsley. Recognizing and avoiding siRNA off-target effects for target identification and therapeutic application. Nat Rev Drug Discov 2010; 9(1): 57–67 https://doi.org/10.1038/nrd3010
pmid: 20043028
BBMandal, A Grinberg, ESGil, BPanilaitis, DLKaplan. High-strength silk protein scaffolds for bone repair. Proc Natl Acad Sci USA 2012; 109(20): 7699–7704 https://doi.org/10.1073/pnas.1119474109
pmid: 22552231
LGSicchieri, GE Crippa, PTde Oliveira, MMBeloti, ALRosa. Pore size regulates cell and tissue interactions with PLGA-CaP scaffolds used for bone engineering. J Tissue Eng Regen Med 2012; 6(2): 155–162 https://doi.org/10.1002/term.422
pmid: 21446054
238
ALZajac, DE Discher. Cell differentiation through tissue elasticity-coupled, myosin-driven remodeling. Curr Opin Cell Biol 2008; 20(6): 609–615 https://doi.org/10.1016/j.ceb.2008.09.006
pmid: 18926907
239
AMYousefi, ME Hoque, RGPrasad, NUth. Current strategies in multiphasic scaffold design for osteochondral tissue engineering: a review. J Biomed Mater Res A 2015; 103(7): 2460–2481 https://doi.org/10.1002/jbm.a.35356
pmid: 25345589
240
RChapanian, BG Amsden. Combined and sequential delivery of bioactive VEGF165 and HGF from poly(trimethylene carbonate) based photo-cross-linked elastomers. J Control Release 2010; 143(1): 53–63 https://doi.org/10.1016/j.jconrel.2009.11.025
pmid: 19961885