Hanzheng Chen

First Affiliated Hospital of Guangzhou Medical University

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Yongchang Yao

First Affiliated Hospital of Guangzhou Medical University

Shujiang Zhang

Institute of Vegetables and Flowers

Shicong Zheng

Guangzhou Medical University

Tingshuai Zhang

First Affiliated Hospital of Guangzhou Medical University

Yi Chen

Sun Yat-sen University

Yi Chen

Columbia University

Wei Zhou

South China Agricultural University

Bo Bai

First Affiliated Hospital of Guangzhou Medical University

Ri-Xu Liu

Jinan University

Hui Gao

Tianjin Polytechnic University

Cooperative Institutions

Guangzhou Medical University

First Affiliated Hospital of Guangzhou Medical University

Key Laboratory of Guangdong Province

Nanjing Medical University

Capital Medical University

Lanzhou University

Lanzhou University Second Hospital

University of Chinese Academy of Sciences

Chinese Academy of Sciences

First Affiliated Hospital of Jinan University

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Experimental study of three-dimensional co-culture system promoting dedifferentiated chondrocyte redifferentiation

Chin J Joint Surg(Electronic Edition) (2019)

Tingshuai Zhang Jianyu Zou Hanzheng Chen Ri-Xu Liu Shicong Zheng

Objective To investigate the effect of alginate hydrogel 3D co-culture on redifferentiation of dedifferentiated chondrocytes. Methods The first generation (P1) chondrocytes and the fourth generation (P4) chondrocytes were co-cultured with ATDC5 at the ratio of 3: 1, and wee named as AP1 and AP4 respectively. Another 3D culture system consisting of single P1, P4 and ATDC5 was established, and was named as P1, P4 and ATDC, respectively. All the groups were cultured in the chondrocyte-inducing medium with the supply of TGF-β3. After 28 days, the expression of collagen typeⅠ (ColⅠ), collagen typeⅡ (ColⅡ) and aggrecan (Acan) genes was assayed by Q-PCR. Histological staining was performed. The cartilage-related genes (Col Ⅱ and Acan) of each group were compared. The results were analyzed by Bonferroni test. Results The expression of ColⅡ and Acan in AP4 group was significantly up-regulated compared to P1 and P4 groups (ColⅡ: F=38.41, P<0.01, Acan: F=5, P<0.01 ), and the deposition of relative protein products could also be clearly observed on histological staining. Conclusion The 3D co-culture system can make the dedifferentiated chondrocytes regain their unique phenotype, the mechanism of which involves cellular factors and the cell-cell connection. Key words: Transforming growth factor beta3; Hydrogel; Collagen type Ⅰ; Collagen type Ⅱ; Biocompatible materials; Chondrocyte; Dedifferentiation

Aggrecan

Type II collagen

Type I collagen

10.3877/cma.j.issn.1674-134x.2019.06.008

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Enhanced chondrogenesis in a coculture system with genetically manipulated dedifferentiated chondrocytes and ATDC5 cells

Biotechnology and Bioengineering (2020)

Yongchang Yao Tingshuai Zhang Hanzheng Chen Shicong Zheng Yi Chen

Abstract Articular cartilage repair after injury is a great challenge worldwide due to its nerveless and avascular features. Tissue engineering is proposed as a promising alternative for cartilage regeneration. In this study, an adenoviral vector carrying the transforming growth factor‐β3 (TGF‐β3) gene was constructed and introduced into dedifferentiated chondrocytes, which were then cocultured with ATDC5 cells in an alginate hydrogel system. The results showed that the experimental groups exhibited better cell viability and higher levels of cartilage‐related genes than the control groups. In this coculture system, the chondrogenic differentiation of ATDC5 cells was effectively induced by TGF‐β3 and other latent cytokines that were produced by the transfected chondrocytes. Thus, this method can avoid the degradation of exogenous TGF‐β3, and it can protect ATDC5 cells during virus transfection to maintain cell viability and chondrogenic differentiation capability. Taken together, this study provides fresh insights for applying this genetically manipulated coculture system to cartilage repair in the future.

Chondrogenesis

Articular cartilage repair

Viability assay

SOX9

10.1002/bit.27482

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Effect of passage number of genetically modified TGF-β3 expressing primary chondrocytes on the chondrogenesis of ATDC5 cells in a 3D coculture system

Biomedical Materials (2022)

Ke Chen Hanzheng Chen Hui Gao Wei Zhou Shicong Zheng

Abstract Due to the lack of blood vessels, nerves and lymphatics, articular cartilage is difficult to repair once damaged. Tissue engineering is considered to be a potential strategy for cartilage regeneration. Successful tissue engineering strategies depend on the effective combination of biomaterials, seed cells and biological factors. In our previous study, a genetically modified coculture system with chondrocytes and ATDC5 cells in an alginate hydrogel has exhibited a superior ability to enhance chondrogenesis. In this study, we further evaluated the influence of chondrocytes at various passages on chondrogenesis in the coculture system. The results demonstrated that transfection efficiency was hardly influenced by the passage number of chondrocytes. The coculture system with passage 5 (P5) chondrocytes had a better effect on chondrogenesis of ATDC5 cells, while chondrocytes in this coculture system presented higher levels of dedifferentiation than other groups with P1 or P3 chondrocytes. Therefore, P5 chondrocytes were shown to be more suitable for the coculture system, as they accumulated in sufficient cell numbers with more passages and had a higher level of dedifferentiation, which was prone to form a favorable niche for chondrogenesis of ATDC5 cells. This study may provide fresh insights for future cartilage tissue engineering strategies with a combination of a coculture system and advanced biomaterials.

Chondrogenesis

Articular cartilage repair

10.1088/1748-605x/ac489e

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Progress of biomaterials for bone tumor therapy

Journal of Biomaterials Applications (2021)

Hanzheng Chen Yongchang Yao

Bone tumors are currently a major clinical challenge. In recent decades, strategies using well-designed versatile biomaterials for the treatment of bone tumors have emerged and attracted extensive research interest. Suitable biomaterials not only facilitate repair for bone defects aroused by surgical intervention but also help deliver antineoplastic drugs to the target site or provide photothermal/magnetothermal therapy to kill bone tumor cells. Thus, the development of biomaterials exhibits a great perspective for future bone tumor treatment. We summarize the recent progress of versatile biomaterials for bone tumor therapy, with an emphasis on photothermal/magnetothermal therapy and drug delivery. With the further understanding and development of biomaterials, multifunctional biomaterials have been proposed for bone tumor treatment. Through the interdisciplinary cooperation from the fields of biomedicine, clinical medicine and engineering, multifunctional biomaterials will perfectly match individual bone defects in the clinic with low cost in the future.

Biomedicine

10.1177/08853282211035236

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Gene-modified BMSCs encapsulated with carboxymethyl cellulose facilitate osteogenesis in vitro and in vivo

Journal of Biomaterials Applications (2020)

Shicong Zheng Hanzheng Chen Tingshuai Zhang Yongchang Yao Yi Chen

Critical size bone defects are one of the most serious complications in orthopedics due to the lack of effective osteogenesis treatment. We fabricated carboxymethyl cellulose with phenol moieties (CMC-ph) microcapsules loaded with gene-modified rat bone mesenchymal stem cells (rBMSCs) that secrete hBMP2 following doxycycline (DOX) induction. The results showed that the morphology of microcapsules was spherical, and their diameters have equally distributed in the range of 100–150 μm; the viability of rBMSCs was unchanged over time. Through real-time PCR and Western blot analyses, the rBMSCs in microcapsules were found to secrete hBMP2 and to have upregulated mRNA and protein expression of osteogenesis-related genes in vitro and in vivo. Furthermore, the in vivo results suggested that the group with the middle concentration of cells expressed the highest amount of osteogenic protein over time. In this study, we showed that gene-modified rBMSCs in CMC-ph microcapsules had good morphology and viability. The BMP2–BMSCs/CMC-Ph microcapsule system could upregulate osteogenic mRNA and protein in vitro and in vivo. Further analysis demonstrated that the medium concentration of cells had a suitable density for transplantation in nude mice. Therefore, BMP2–BMSCs/CMC-Ph microcapsule constructs have potential for bone regeneration in vivo.

Carboxymethyl cellulose

10.1177/0885328220948030

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