Expression Patterns of &lt;i&gt;Ets2 &lt;/i&gt;Protein Correlate with Bone-Specific Proteins in Cell-Seeded Three-Dimensional Bone Constructs

Wanschitz, Felix; Stein, Elisabeth; Sutter, Walter; Kneidinger, Doris; Smolik, Konstantin; Watzinger, Franz; Turhani, Dritan

doi:10.1159/000107556

Cited by 3 publications

(1 citation statement)

References 79 publications

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“…Allograft use risks disease transmission and has limited availability from young, healthy donors 39 [De Long et al, 2007;Campana et al, 2014]. Consequently, there is increased interest in tissue-40 engineered bone substitutes [Wanschitz et al, 2007;Pina et al, 2017;Shahi et al, 2018;Iaquinta 41 et al, 2019]. 42…”

Section: Introduction 29mentioning

confidence: 99%

Investigating the Osteoinductive Potential of a Decellularized Xenograft Bone Substitute

Bracey

Jinnah

Willey

et al. 2018

Preprint

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1Bone grafting is the second most common tissue transplantation procedure worldwide. 2The gold standard for bone grafting is the autograft; however, due to morbidity and limited 3 supply, new alternatives, including allograft and tissue-engineered bone substitutes, are needed 4 to satisfy long-term demand. One of the most desired properties of tissue-engineered bone 5 substitutes is osteoinductivity, defined as the ability to stimulate primitive cells to differentiate 6 into a bone forming lineage. In the current study, we treated porcine bone with a decellularization 7 protocol to produce a bone scaffold. We examined whether the scaffold possessed osteoinductive 8 potential and could be used to create a tissue-engineered bone microenvironment. To test if the 9 bone scaffold was a viable host, pre-osteoblasts were seeded, incubated in vitro, and analyzed for 10 markers of osteogenic differentiation. To assess these properties in vivo, scaffolds with and 11 without pre-osteoblasts pre-seeded were subcutaneously implanted in mice for four weeks. The 12 scaffolds underwent micro-computed tomography (microCT) scanning before implantation. After 13 retrieval, the scaffolds were analyzed for osteogenic differentiation or re-scanned by microCT to 14 assess new bone formation with the subsequent histological assessment. The osteoinductive 15 potential was observed in vitro with similar osteogenic markers being expressed as observed in 16 demineralized bone matrix and significantly greater expression of these markers than controls. 17By microCT, paired t-tests demonstrated significantly increased bone volume:total volume 18 (BV/TV) and trabecular thickness (Tb.Th) after explantation in all groups. Pentachrome staining 19 demonstrated osteogenesis within the scaffold, and angiogenesis in the scaffold was confirmed 20 by CD31 staining for blood vessels. These results demonstrate that porcine bone maintains its 21 osteoinductive properties after the application of a novel decellularization and oxidation protocol. 22Future work must be performed to definitively prove osteogenesis of human mesenchymal stem 23 cells, biocompatibility in large animal models, and osteoinduction/osseointegration in a relevant 24 clinical model in vivo. The ability to create a functional bone microenvironment using 25 decellularized xenografts will impact regenerative medicine, orthopaedic reconstruction, and 26 could be used in the research of multiple diseases. 27 28

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Section: Introduction 29mentioning

confidence: 99%

Investigating the Osteoinductive Potential of a Decellularized Xenograft Bone Substitute

Bracey

Jinnah

Willey

et al. 2018

Preprint

View full text Add to dashboard Cite

show abstract

Identification of Key Osteoporosis Genes Through Comparative Analysis of Men's and Women's Osteoblast Transcriptomes

Chen,

Li,

Wang

et al. 2023

Calcif Tissue Int

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Investigating the Osteoinductive Potential of a Decellularized Xenograft Bone Substitute

Bracey

Jinnah

Willey

et al. 2019

Cells Tissues Organs

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Bone grafting is the second most common tissue transplantation procedure worldwide. One of the alternative methods for bone repair under investigation is a tissue-engineered bone substitute. An ideal property of tissue-engineered bone substitutes is osteoinductivity, defined as the ability to stimulate primitive cells to differentiate into a bone-forming lineage. In the current study, we use a decellularization and oxidation protocol to produce a porcine bone scaffold and examine whether it possesses osteoinductive potential and can be used to create a tissue-engineered bone microenvironment. The decellularization protocol was patented by our lab and consists of chemical decellularization and oxidation steps using combinations of deionized water, trypsin, antimicrobials, peracetic acid, and triton-X100. To test if the bone scaffold was a viable host, preosteoblasts were seeded and analyzed for markers of osteogenic differentiation. The osteoinductive potential was observed in vitro with similar osteogenic markers being expressed in preosteoblasts seeded on the scaffolds and demineralized bone matrix. To assess these properties in vivo, scaffolds with and without preosteoblasts preseeded were subcutaneously implanted in mice for 4 weeks. MicroCT scanning revealed 1.6-fold increased bone volume to total volume ratio and 1.4-fold increase in trabecular thickness in scaffolds after implantation. The histological analysis demonstrates new bone formation and blood vessel formation with pentachrome staining demonstrating osteogenesis and angiogenesis, respectively, within the scaffold. Furthermore, CD31+ staining confirmed the endothelial lining of the blood vessels. These results demonstrate that porcine bone maintains its osteoinductive properties after the application of a patented decellularization and oxidation protocol developed in our laboratory. Future work must be performed to definitively prove osteogenesis of human mesenchymal stem cells, biocompatibility in large animal models, and osteoinduction/osseointegration in a relevant clinical model in vivo. The ability to create a functional bone microenvironment using decellularized xenografts will impact regenerative medicine, orthopedic reconstruction, and could be used in the research of multiple diseases.

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Expression Patterns of <i>Ets2 </i>Protein Correlate with Bone-Specific Proteins in Cell-Seeded Three-Dimensional Bone Constructs

Cited by 3 publications

References 79 publications

Investigating the Osteoinductive Potential of a Decellularized Xenograft Bone Substitute

Investigating the Osteoinductive Potential of a Decellularized Xenograft Bone Substitute

Identification of Key Osteoporosis Genes Through Comparative Analysis of Men's and Women's Osteoblast Transcriptomes

Investigating the Osteoinductive Potential of a Decellularized Xenograft Bone Substitute

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