Vascularization in Bone Tissue Engineering Constructs

Mercado-Pagán, Àngel E.; Stahl, Alexander M.; Shanjani, Yaser; Yang, Yunzhi Peter

doi:10.1007/s10439-015-1253-3

Cited by 242 publications

(202 citation statements)

References 122 publications

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“…6). Without prevascularization of the scaffold, it may take too long to form the vasculature upon implantation which would result in an ischemic condition before the desired neo-bone could form and integrate into the defect site [55]. Absence of a uniform vasculature is especially detrimental for scaffolds of clinically relevant sizes.…”

Section: Discussionmentioning

confidence: 99%

Effect of prevascularization on in vivo vascularization of poly(propylene fumarate)/fibrin scaffolds

et al. 2016

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The importance of vascularization in the field of bone tissue engineering has been established by previous studies. The present work proposes a novel poly(propylene fumarate) (PPF)/fibrin composite scaffold for the development of vascularized neobone tissue. The effect of prevascularization (i.e., in vitro pre-culture prior to implantation) with human mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells (HUVECs) on in vivo vascularization of scaffolds was determined. Five conditions were studied: no pre-culture (NP), 1 week preculture (1P), 2 week pre-culture (2P), 3 week pre-culture (3P), and scaffolds without cells (control, C). Scaffolds were implanted subcutaneously in a severe combined immunodeficiency (SCID) mice model for 9 days. During in vitro studies, CD31 staining showed a significant increase in vascular network area over 3 weeks of culture. Vascular density was significantly higher in vivo when comparing NP to 3P groups. Immunohistochemical staining of human CD-31 expression indicated spreading of vascular networks with increasing pre-culture time. These vascular networks were perfused with mouse blood indicated by perfused lectin staining in human CD-31 positive vessels. Our results demonstrate that in vitro prevascularization supports in vivo vascularization in PPF/fibrin scaffolds.

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Section: Discussionmentioning

confidence: 99%

Effect of prevascularization on in vivo vascularization of poly(propylene fumarate)/fibrin scaffolds

et al. 2016

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“…Porosity, swelling capacity, water absorption, compressive strength and compressive modulus analysis indicated that the physical properties of the scaff old met the basic requirements for use in tissue engineering [30][31][32][33] (Tables 1 and 2). One hour after the start of the experiment, the pH was approximately 7.0.…”

Section: Porosity Swelling Capacity Water Absorption Capacity Mechmentioning

confidence: 99%

Withdrawal: Synthesis of a Novel bFGF/nHAP/COL Bone Tissue Engineering Scaffold for Mandibular Defect Regeneration in a Rabbit Model

Yue

Tan

Zhao

et al. 2018

J. Hard Tissue Biology.

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In bone tissue engineering, scaffold fabrication and biocompatibility are crucial concerns. Many scaffold materials have been explored, among which nanometer hydroxyapatite (nHAP) and collagen (COL) are commonly used. Additionally, growth factors can be used to modify scaff olds. In this study, lyophilization technology was used to build a scaff old comprising basic fi broblast growth factor (bFGF), nHAP and COL for the fi rst time. The resulting scaff old was characterized. bFGF release from the scaff old was assessed by ELISA. Bone marrow mesenchymal stem cells (BMSCs) were prepared and seeded onto the scaff old to test in vitro biological compatibility. A scanning electron microscope was used to observe the scaff old and evaluate BMSC morphology, and the cells were counted to detect early cell adhesion. Cell proliferation and activity were assessed by a cell counting kit-8 assay and measurement of alkaline phosphatase activity, respectively. Bilateral mandibular defects were prepared in 12 New Zealand rabbits and repaired using scaff olds. The rabbits were divided into four groups: a group treated with allogeneic BMSC-seeded bFGF/nHAP/COL scaff old, a group treated with allogeneic BMSC-seeded nHAP/COL scaff old, a group treated with nHAP/COL scaff old alone, and an untreated control group. After 12 weeks, three-dimensional computerized tomography examination, computerized tomography value measurement, gross observation and hematoxylin and eosin stain staining were conducted. SPSS17.0 software was used for data analysis. The gross morphology conformed to the characteristics of a tissue engineering scaff old. The bFGF/nHAP/COL scaff old promoted BMSC adhesion, proliferation and diff erentiation and hence promoted good bone formation, without exhibiting biological toxicity. Our fi ndings show that the bFGF/nHAP/COL scaff old has good physical properties and biocompatibility in vitro, and can be used to promote osteogenesis after in vivo implantation.

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“…To accelerate the engraftment and improve the survival of such engineered bone tissues, the focus has recently been directed toward their prevascularization. [3][4][5][6][7][8][9] Additionally and equally important, the acquiring of knowledge on vascularization of bone mimicking tissues in combination with novel tailorable biomaterials and advanced 3D manufacturing processes will make the creation of physiologically relevant in vitro bone models become tangible. Such models would allow for the study and testing of healing inducing treatments under fully defi ned and reproducible experimental conditions.…”

mentioning

confidence: 99%

Dual Role of Mesenchymal Stem Cells Allows for Microvascularized Bone Tissue‐Like Environments in PEG Hydrogels

Blache

Metzger

Vallmajó-Martín

et al. 2015

Adv Healthcare Materials

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In vitro engineered tissues which recapitulate functional and morphological properties of bone marrow and bone tissue will be desirable to study bone regeneration under fully controlled conditions. Among the key players in the initial phase of bone regeneration are mesenchymal stem cells (MSCs) and endothelial cells (ECs) that are in close contact in many tissues. Additionally, the generation of tissue constructs for in vivo transplantations has included the use of ECs since insufficient vascularization is one of the bottlenecks in (bone) tissue engineering. Here, 3D cocultures of human bone marrow derived MSCs (hBM-MSCs) and human umbilical vein endothelial cells (HUVECs) in synthetic biomimetic poly(ethylene glycol) (PEG)-based matrices are directed toward vascularized bone mimicking tissue constructs. In this environment, bone morphogenetic protein-2 (BMP-2) or fibroblast growth factor-2 (FGF-2) promotes the formation of vascular networks. However, while osteogenic differentiation is achieved with BMP-2, the treatment with FGF-2 suppressed osteogenic differentiation. Thus, this study shows that cocultures of hBM-MSCs and HUVECs in biological inert PEG matrices can be directed toward bone and bone marrow-like 3D tissue constructs.

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Vascularization in Bone Tissue Engineering Constructs

Cited by 242 publications

References 122 publications

Effect of prevascularization on in vivo vascularization of poly(propylene fumarate)/fibrin scaffolds

Effect of prevascularization on in vivo vascularization of poly(propylene fumarate)/fibrin scaffolds

Withdrawal: Synthesis of a Novel bFGF/nHAP/COL Bone Tissue Engineering Scaffold for Mandibular Defect Regeneration in a Rabbit Model

Dual Role of Mesenchymal Stem Cells Allows for Microvascularized Bone Tissue‐Like Environments in PEG Hydrogels

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