Prefabrication of vascularized grafts based on pre-differentiated adipose derived stem cells, fibrin sealant and porous calcium phosphate cement scaffold

doi:10.3969/j.issn.2095-4344.2013.51.004

Abstract

Abstract:

BACKGROUND: Construction of vascularized bone substitutes to mimic free vascularized fibular grafting in treating large bone defects still remains challenges to researchers during the past years.
OBJECTIVE: To design and construct a new vascularized tissue-engineered bone graft using pre-differentiated adipose derived stem cells, fibrin sealant and porous calcium phosphate cement scaffold.
METHODS: Adipose derived stem cells isolated from rats were directly differentiated to endothelial cells and then incorporated in fibrin sealant and porous calcium phosphate cement scaffolds in vitro. Subsequently, the different composites of the three groups including vascularized tissue-engineered bone scaffold (group A), fibrin sealant and porous calcium phosphate cement scaffold (group B) and porous calcium phosphate cement scaffold (group C) were directly embedded into the quadriceps of the rats. Histological quantitative analysis and western blot assay were conducted 2 and 4 weeks after implantation.
RESULTS AND CONCLUSION: The pre-differentiated adipose derived stem cells were demonstrated in good condition after 7 days co-culturing with the fibrin sealant and porous calcium phosphate cement scaffold. The results of in vivo experiments showed that the scaffolds were in-grown together with fibrous connective tissues and blood vessels. Newly formed vessels and immature capillaries were observed in the group A. The vessel density, vessel diameter and vascular endothelial growth factor C expression in the group A were significantly higher than those in the groups B and C. Our findings demonstrated that compared with simply fibrin sealant and porous calcium phosphate cement scaffold, the combination of pre-differentiated adipose derived stem cells (endothelial differentiation) and fibrin sealant can achieve rapid angiogenesis of porous calcium phosphate cement scaffold.

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程

全文链接：

Key words: biocompatible materials, stem cells, fibrin tissue adhesive, calcium phosphates

CLC Number:

R318

Yang Pei, Huang Xin, Wang Chun-sheng, Wang Kun-zheng. Prefabrication of vascularized grafts based on pre-differentiated adipose derived stem cells, fibrin sealant and porous calcium phosphate cement scaffold[J]. Chinese Journal of Tissue Engineering Research, 2013, 17(51): 8801-8808.

Figures/Tables 4

References

[1]Oliveira MR,Martins Ed,Célio-Mariano R,et al.Tissue engineering: using collagen type I matrix for bone healing of bone defects.J Craniofac Surg.2013;24(2):e394-396.

[2]Lu H,Lv L,Dai Y,et al.Porous Chitosan Scaffolds with Embedded Hyaluronic Acid/Chitosan/Plasmid-DNA Nanoparticles Encoding TGF-β1 Induce DNA Controlled Release, Transfected Chondrocytes, and Promoted Cell Proliferation.PLOS One.2013;8(7):e69950.

[3]Georgiou M,Bunting SC,Davies HA,et al.Engineered neural tissue for peripheral nerve repair.Biomaterials.2013; 34(30): 7335-7343.

[4]Kokemueller H,Spalthoff S,Nolff M,et al.Prefabrication of vascularized bioartificial bone grafts in vivo for segmental mandibular reconstruction: experimental pilot study in sheep and first clinical application.Int J Oral Maxillofac Surg.2010; 39(4):379-387.

[5]Bleiziffer O,Hammon M,Naschberger E,et al.Endothelial progenitor cells are integrated in newly formed capillaries and alter adjacent fibrovascular tissue after subcutaneous implantation in a fibrin matrix.J Cell Mol Med.2011;15(11): 2452-2461.

[6]Rouwkema J,de Boer J,Van Blitterswijk CA.Endothelial cells assemble into a 3-dimensional prevascular network in a bone tissue engineering construct.Tissue Eng.2006;12(9): 2685- 2693.

[7]Oswald J,Boxberger S,Jorgensen B,et al.Mesenchymal stem cells can be differentiated into endothelial cells in vitro.Stem Cells.2004; 22(3):377-384.

[8]Shojaei S,Tafazzoli-Shahdpour M,Shokrgozar MA,et al.Effects of mechanical and chemical stimuli on differentiation of human adipose-derived stem cells into endothelial cells.Int J Artif Organs.2013;36(9):663-673.

[9]Liu Y,Zhang Z,Qin Y,et al.A new method for Schwann-like cell differentiation of adipose derived stem cells.Neurosci Lett. 2013;551:79-83.

[10]Wosnitza M,Hemmrich K,Groger A,et al.Plasticity of human adipose stem cells to perform adipogenic and endothelial differentiation. Differentiation.2007;75:12-23.

[11]Zhang K,Zhang Y,Yan S,et al.Repair of an articular cartilage defect using adipose-derived stem cells loaded on a polyelectrolyte complex scaffold based on poly(l-glutamic acid) and chitosan.Acta Biomater. 2013;9(7):7276-7288.

[12]Yamada Y,Boo JS,Ozawa R,et al.Bone regeneration following injection of mesenchymal stem cells and fibrin glue with a biodegradable scaffold .J Craniomaxillofac Surg.2003;31(1): 27-33.

[13]Liang H,Yin Y,Lin T,et al.Transplantation of bone marrow stromal cells enhances nerve regeneration of the corticospinal tract and improves recovery of neurological functions in a collagenase-induced rat model of intracerebral hemorrhage.Mol Cells.2013;36(1):17-24.

[14]Aberg J,Engstrand J,Engqvist H.Influence of particle size on hardening and handling of a premixed calcium phosphate cement.J Mater Sci Mater Med.2013;24(4):829-835.

[15]Francis CS,Wong RK,Cohen SR.Endoscopic delivery of calcium phosphate cement for secondary craniofacial reconstruction.J Craniofac Surg. 2012;23(7 Suppl 1): 2057-2060.

[16]Gradl G,Knobe M,Stoffel M,et al.Biomechanical evaluation of locking plate fixation of proximal humeral fractures augmented with calcium phosphate cement.J Orthop Trauma. 2013;27(7):399-404.

[17]Luvizuto ER,Queiroz TP,Margonar R,et al.Osteoconductive properties of β-tricalcium phosphate matrix, polylactic and polyglycolic acid gel, and calcium phosphate cement in bone defects.J Craniofac Surg.2012;23(5):e430-433.

[18]张建明,张西正,李瑞欣,等.快速成型方法制备组织工程支架的研究与应用[J].中国组织工程研究,2013,17(8):1435-1440.

[19]Katase H,Kanazawa M,Inokoshi M,et al.Face simulation system for complete dentures by applying rapid prototyping.J Prosthet Dent. 2013;109(6):353-360.

[20]Xu Y,Liu L,Li Y,et al.Myelin-forming ability of Schwann cell-like cells induced from rat adipose-derived stem cells in vitro. Brain Res. 2008;1239:49-55.

[21]Yang Z,Huang CY,Candiotti KA,et al.Sox-9 facilitates differentiation of adipose tissue-derived stem cells into a chondrocyte-like phenotype in vitro.J Orthop Res.2011; 29(8): 1291-1297.

[22]Smith T,Goede F,Struck M,et al.Arthroscopic posterior shoulder stabilization with an iliac bone graft and capsular repair: a novel technique.Arthrosc Tech.2012;1(2):e181-185.

[23]Lee YH,Wang JK,Hwang K.Correction of enophthalmos with rib bone segment and diced cartilage grafts.J Craniofac Surg. 2012;23(6):1917-1920.

[24]Eward WC,Rineer CA,Urbaniak JR,et al.The vascularized fibular graft in precollapse osteonecrosis: is long-term hip preservation possible? Clin Orthop Relat Res.2012;470(10): 2819-2826.

[25]Van der Stok J,Van Lieshout EM,El-Massoudi Y,et al.Bone substitutes in the Netherlands - a systematic literature review. Acta Biomater.2011;7(2):739-750.

[26]Khouri RK,Upton J,Shaw WW.Prefabrication of composite free flaps through staged microvascular transfer: an experimental and clinical study.Plast Reconstr Surg.1991; 87(1): 108-115.

[27]Sever C,Uygur F,Kose GT,et al.Prefabrication of vascularized bone graft using an interconnected porous calcium hydroxyapatite ceramic in presence of vascular endothelial growth factor and bone marrow mesenchymal stem cells: Experimental study in rats.Indian J Plast Surg. 2012;45(3): 444-452.

[28]Mastrogiacomo M,Scaglione S,Martinetti R,et al.Role of scaffold internal structure on in vivo bone formation in macroporous calcium phosphate bioceramics.Biomaterials. 2006;27(17):3230-3237.

[29]De Oliveira JF,De Aguiar PF,Rossi AM,et al.Effect of process parameters on the characteristics of porous calcium phosphate ceramics for bone tissue scaffolds.Artif Organs. 2003; 27(5):406-411.

[30]Lee M,Wu BM,Dunn JC.Effect of scaffold architecture and pore size on smooth muscle cell growth.J Biomed Mater Res A.2008;87(4):1010-1016.

[31]Kuboki Y,Jin Q,Takita H.Geometry of carriers controlling phenotypic expression in BMP-induced osteogenesis and chondrogenesis.J Bone Joint Surg Am.2001;83-A(Pt2):S105.

[32]Lu JX,Flautre B,Anselme K,et al.Role of interconnections in porous bioceramics on bone recolonization in vitro and in vivo.J Mater Sci Mater Med.1999;10(2):111-120.

[33]Hosoya M,Maruoka Y,Oda M,et al.Bone with a vascular flap induced from fat tissue with the use of rhBMP-2 in rats.J Dent Res.2003;82(8): 581-584.

[34]Terheyden H,Knak C,Jepsen S,et al.Mandibular reconstruction with a prefabricated vascularized bone graft using recombinant human osteogenic protein-1: an experimental study in miniature pigs. Part I: Prefabrication.Int J Oral Maxillofac Surg.2001;30(5):373-379.

[35]杨志明,樊征夫,解慧琪,等.组织工程化人工骨血管化的研究[J].中华显微外科杂志,2002,25(2):119-122.

[36]Matsuda K,Falkenberg KJ,Woods AA,et al.Adipose-derived stem cells promote angiogenesis and tissue formation for in vivo.Tissue Eng.2013;(11-12):1327-1335.

[37]Rath SN,Arkudas A,Lam CX,et al.Development of a pre-vascularized 3D scaffold-hydrogel composite graft using an arterio-venous loop for tissue engineering applications.J Biomater Appl.2012;27(3):277-289.

[38]Rath SN,Pryymachuk G,Bleiziffer OA,et al.Hyaluronan-based heparin-incorporated hydrogels for generation of axially vascularized bioartificial bone tissues: in vitro and in vivo evaluation in a PLDLLA-TCP-PCL-composite system.J Mater Sci Mater Med.2011;22(5):1279-1291.

[39]Jeong H,Yim HW,Cho Y,et al.The effect of rigorous study design in the research of autologous bone marrow-derived mononuclear cell transfer in patients with acute myocardial infarction.Stem Cell Res Ther. 2013;4(4):82.

[40]Zimmet H,Porapakkham P,Porapakkham P,et al.Short-and long-term outcomes of intracoronary and endogenously mobilized bone marrow stem cells in the treatment of ST-segment elevation myocardial infarction: a meta-analysis of randomized control trials.Eur J Heart Fail.2012;14(1): 91-105.

[41]Zuk PA,Zhu M,Mizuno H,et al.Multilineage cells from human adipose tissue: implications for cell-based therapies.Tissue Eng. 2001;7(2):211-218.

[42]Zuk PA,Zhu M,Ashjian P,et al.Human adipose tissue is a source of multipotent stem cells.Mol Biol Cell.2002;13(12): 4279-1295.

[43]Shi Z,Neoh KG,Kang ET,et al.Enhanced endothelial differentiation of adipose-derived stem cells by substrate nanotopography.J Tissue Eng Regen Med.2012 May 24. doi: 10.1002/term.1496.