Bone tissue engineering scaffolds with HUVECs/hBMSCs cocultured on 3D-printed composite bioactive ceramic scaffolds promoted osteogenesis/angiogenesis

Liu, Xiao; Zhao, Naru; Liang, Haifeng; Tan, Bizhi; Huang, Fangli; Hu, Hao; Chen, Yan; Wang, Gang; Ling, Zemin; Li, Chun; Miao, Yali; Wang, Yingjun; Zou, Xuenong

doi:10.1016/j.jot.2022.10.008

Cited by 17 publications

(9 citation statements)

References 48 publications

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“…Also, bone regeneration trends to be more precise and intelligent, as well as closely relative with 3D technology in the future . The 3D-printed bosutinib loaded scaffold has good biocompatibility, biodegradability, and capability to enhance osteogenesis for personalized bone defect repair, thus having the potential to be clinically translated . Further research should be undertaken to explore a deeper mechanism and investigate the effect of bosutinib on large animals.…”

Section: Discussionmentioning

confidence: 99%

Bosutinib Laden Three-Dimensional Printed Zein Scaffolds Promote Osteogenesis

Zou,

Yin,

Lei

et al. 2024

ACS Appl. Polym. Mater.

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Bone defect repair remains a challenge to be addressed in clinical practice, and existing bone grafting methods still have disadvantages and limitations. Drugs or cytokines laden into bioactive scaffolds to promote bone regeneration is a promising strategy to deal with the problem; thus, it is meaningful to develop drugs and scaffolds with osteogenic abilities. Drug repurposing is an admirable method to find unknown usages of old drugs for enhancing osteogenic differentiation. In this study, by screening an approved drug library consisting of 2040 compounds, bosutinib, a tyrosine kinase inhibitor, was identified to promote osteogenic differentiation in vitro. The observed effect was further confirmed using polymerase chain reaction (PCR), western blot, Alizarin Red staining, and alkaline phosphatase (ALP) activity staining. Subsequently, transcriptome sequencing was performed to elucidate the osteogenesis mechanism of bosutinib, and a potential target gene, Storkhead box 1 (STOX1), which was not reported to be associated with osteogenesis, was found. By a gene knockdown strategy, we provided preliminary evidence that bosutinib can promote osteogenic differentiation by mediating STOX1. Furthermore, in order to maximize the local effects of drug and minimize its side effects, a bosutinib laden three-dimensional (3D)-printed zein scaffold was constructed and characterized, and its ability of promoting osteogenesis was evaluated in vivo. Micro-CT analysis and histological staining demonstrated that the scaffold effectively promoted bone regeneration. All in all, our study provides a therapeutic option for the treatment of bone defects.

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Section: Discussionmentioning

confidence: 99%

Bosutinib Laden Three-Dimensional Printed Zein Scaffolds Promote Osteogenesis

Zou,

Yin,

Lei

et al. 2024

ACS Appl. Polym. Mater.

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“…In contrast, HUVECs, recognized as mature endothelial cells, can produce the necessary factors and proteins for angiogenesis, subsequently fostering neointima formation ( Khayat et al, 2017 ). During co-culture, the microvessels formed by HUVECs facilitate the supply of nutrients and oxygen to MSCs, thereby bolstering their growth and differentiation ( Liu et al, 2022b ; Li et al, 2022 ). Consequently, we hypothesize that incorporating HUVECs into the co-culture could compensate for the lower innate angiogenesis potential of the GS and potentially foster further differentiation of the stem cell components within the system.…”

Section: Discussionmentioning

confidence: 99%

Co-culture of STRO1 + human gingival mesenchymal stem cells and human umbilical vein endothelial cells in 3D spheroids: enhanced in vitro osteogenic and angiogenic capacities

Liu,

Chen,

Zhou

et al. 2024

Front. Cell Dev. Biol.

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Stem cell spheroid is a promising graft substitute for bone tissue engineering. Spheroids obtained by 3D culture of STRO1+ Gingival Mesenchymal Stem Cells (sGMSCs) (sGMSC spheroids, GS) seldom express angiogenic factors, limiting their angiogenic differentiation in vivo. This study introduced a novel stem cell spheroid with osteogenic and angiogenic potential through 3D co-culture of sGMSCs and Human Umbilical Vein Endothelial Cells (HUVECs) (sGMSC/HUVEC spheroids, GHS). GHS with varying seeding ratios of sGMSCs to HUVECs (GHR) were developed. Cell fusion within the GHS system was observed via immunofluorescence. Calcein-AM/PI staining and chemiluminescence assay indicated cellular viability within the GHS. Furthermore, osteogenic and angiogenic markers, including ALP, OCN, RUNX2, CD31, and VEGFA, were quantified and compared with the control group comprising solely of sGMSCs (GS). Incorporating HUVECs into GHS extended cell viability and stability, initiated the expression of angiogenic factors CD31 and VEGFA, and upregulated the expression of osteogenic factors ALP, OCN, and RUNX2, especially when GHS with a GHR of 1:1. Taken together, GHS, derived from the 3D co-culture of sGMSCs and HUVECs, enhanced osteogenic and angiogenic capacities in vitro, extending the application of cell therapy in bone tissue engineering.

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“…An ideal bone graft for bone tissue engineering should possess exceptional biocompatibility, which is considered a fundamental prerequisite. Recent effort has been made on improving the biocompatibility of bone grafts to enhance their effectiveness in tissue engineering and regenerative medicine application ( Liu et al, 2022 ; Xu et al, 2022 ). Natural materials such as collagen, chitosan, and silk fibroin exhibit favorable biocompatibility by promoting cell adhesion, tissue regeneration, and integration within the body.…”

Section: Discussionmentioning

confidence: 99%

Hydrothermally treated coral scaffold promotes proliferation of mesenchymal stem cells and enhances segmental bone defect healing

Huang,

Park,

Jung

et al. 2023

Front. Bioeng. Biotechnol.

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Introduction: Synthetic hydroxyapatite (HAp) scaffolds have shown promising therapeutic outcomes in both animals and patients. In this study, we aim to evaluate the chemical and physical phenotype, biocompatibility, and bone repair effects of hydrothermally treated coral with natural coral and synthetic HAp.Methods: The phase composition, surface pattern, 3D structures, and porosity of the scaffolds were characterized, and cell viability, proliferation, and osteogenic differentiation of mesenchymal stem cells (MSCs) after seeding onto the scaffold were determined. The scaffolds were implanted into rats to assess their bone repair effects using micro-CT analysis, mechanical testing, and histological staining.Results: The results showed that the phase composition, porous structure, and porosity of hydrothermally treated coral were comparable to pure HAp scaffold. While only the natural coral happens to be dominantly calcium carbonate. Higher cell proliferation and osteogenic differentiation potential were observed in the hydrothermally treated coral scaffold compared to natural coral and pure HAp. Histological results also showed increased new bone formation in the hydrothermally treated coral group.Discussion: Overall, our study suggests that hydrothermal modification enhances the cytocompatibility and therapeutic capacity of coral without altering its physical properties, showing superior effectiveness in bone repair to synthetic HAp.

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Bone tissue engineering scaffolds with HUVECs/hBMSCs cocultured on 3D-printed composite bioactive ceramic scaffolds promoted osteogenesis/angiogenesis

Cited by 17 publications

References 48 publications

Bosutinib Laden Three-Dimensional Printed Zein Scaffolds Promote Osteogenesis

Bosutinib Laden Three-Dimensional Printed Zein Scaffolds Promote Osteogenesis

Co-culture of STRO1 + human gingival mesenchymal stem cells and human umbilical vein endothelial cells in 3D spheroids: enhanced in vitro osteogenic and angiogenic capacities

Hydrothermally treated coral scaffold promotes proliferation of mesenchymal stem cells and enhances segmental bone defect healing

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