Bioinspired stratified electrowritten fiber-reinforced hydrogel constructs with layer-specific induction capacity for functional osteochondral regeneration

Zhiguang Qiao¹, Meifei Lian², Yu Han³, Binbin Sun³, Xing Zhang⁴, Wenbo Jiang³, Huiwu Li⁵, Yongqiang Hao⁶, Kerong Dai⁷

Affiliations

¹ Department of Orthopaedic Surgery, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China; Clinical and Translational Research Center for 3D Printing Technology, Medical 3D Printing Innovation Research Center, Shanghai Ninth People's Hospital, Shanghai Jiao Tong university School of Medicine, Shanghai, 200125, China; Department of Orthopaedic Surgery, Renji Hospital, South Campus, Shanghai Jiao Tong University School of Medicine, Shanghai, 201112, China.
² Clinical and Translational Research Center for 3D Printing Technology, Medical 3D Printing Innovation Research Center, Shanghai Ninth People's Hospital, Shanghai Jiao Tong university School of Medicine, Shanghai, 200125, China; Department of Prosthodontics, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
³ Department of Orthopaedic Surgery, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China; Clinical and Translational Research Center for 3D Printing Technology, Medical 3D Printing Innovation Research Center, Shanghai Ninth People's Hospital, Shanghai Jiao Tong university School of Medicine, Shanghai, 200125, China.
⁴ State Key Laboratory of Mechanical Systems and Vibration, Shanghai Jiao Tong University, Shanghai, 200240, China.
⁵ Department of Orthopaedic Surgery, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
⁶ Department of Orthopaedic Surgery, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China; Clinical and Translational Research Center for 3D Printing Technology, Medical 3D Printing Innovation Research Center, Shanghai Ninth People's Hospital, Shanghai Jiao Tong university School of Medicine, Shanghai, 200125, China. Electronic address: hao_yongqiang@hotmail.com.
⁷ Department of Orthopaedic Surgery, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China; Clinical and Translational Research Center for 3D Printing Technology, Medical 3D Printing Innovation Research Center, Shanghai Ninth People's Hospital, Shanghai Jiao Tong university School of Medicine, Shanghai, 200125, China. Electronic address: krdai@163.com.

PMID: 33120203
DOI: 10.1016/j.biomaterials.2020.120385

Bioinspired stratified electrowritten fiber-reinforced hydrogel constructs with layer-specific induction capacity for functional osteochondral regeneration

Zhiguang Qiao et al. Biomaterials. 2021 Jan.

. 2021 Jan:266:120385.

doi: 10.1016/j.biomaterials.2020.120385. Epub 2020 Oct 17.

Authors

Zhiguang Qiao¹, Meifei Lian², Yu Han³, Binbin Sun³, Xing Zhang⁴, Wenbo Jiang³, Huiwu Li⁵, Yongqiang Hao⁶, Kerong Dai⁷

Affiliations

¹ Department of Orthopaedic Surgery, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China; Clinical and Translational Research Center for 3D Printing Technology, Medical 3D Printing Innovation Research Center, Shanghai Ninth People's Hospital, Shanghai Jiao Tong university School of Medicine, Shanghai, 200125, China; Department of Orthopaedic Surgery, Renji Hospital, South Campus, Shanghai Jiao Tong University School of Medicine, Shanghai, 201112, China.
² Clinical and Translational Research Center for 3D Printing Technology, Medical 3D Printing Innovation Research Center, Shanghai Ninth People's Hospital, Shanghai Jiao Tong university School of Medicine, Shanghai, 200125, China; Department of Prosthodontics, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
³ Department of Orthopaedic Surgery, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China; Clinical and Translational Research Center for 3D Printing Technology, Medical 3D Printing Innovation Research Center, Shanghai Ninth People's Hospital, Shanghai Jiao Tong university School of Medicine, Shanghai, 200125, China.
⁴ State Key Laboratory of Mechanical Systems and Vibration, Shanghai Jiao Tong University, Shanghai, 200240, China.
⁵ Department of Orthopaedic Surgery, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
⁶ Department of Orthopaedic Surgery, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China; Clinical and Translational Research Center for 3D Printing Technology, Medical 3D Printing Innovation Research Center, Shanghai Ninth People's Hospital, Shanghai Jiao Tong university School of Medicine, Shanghai, 200125, China. Electronic address: hao_yongqiang@hotmail.com.
⁷ Department of Orthopaedic Surgery, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China; Clinical and Translational Research Center for 3D Printing Technology, Medical 3D Printing Innovation Research Center, Shanghai Ninth People's Hospital, Shanghai Jiao Tong university School of Medicine, Shanghai, 200125, China. Electronic address: krdai@163.com.

PMID: 33120203
DOI: 10.1016/j.biomaterials.2020.120385

Abstract

Despite significant advances in osteochondral tissue engineering, it remains challenging to successfully reconstruct native-like complex tissues organized in three-dimension with spatially varying compositional, structural and functional properties. In this contribution, inspired by the gradients in extracellular matrix (ECM) composition and collagen fiber architecture in native osteochondral tissue, we designed and fabricated a tri-layered (superficial cartilage (S), deep cartilage (D) and subchondral bone (B) layer) stratified scaffold in which a mesenchymal stem cell (MSC)-laden gelatin methacrylamide (GelMA) hydrogel with zone-specific growth factor delivery was combined with melt electrowritten triblock polymer of poly(ε-caprolactone) and poly(ethylene glycol) (PCEC) networks with depth-dependent fiber organization. Introducing PCEC fibers into the weak GelMA hydrogel contributed to a significant increase in mechanical strength. In vitro biological experiments indicated that the stratified fiber-reinforced and growth factor-loaded hydrogel construct induced the MSCs to differentiate down both the chondrogenic and osteogenic lineages and that the engineered complex exhibited cellular phenotype and matrix accumulation profiles resembling those of the native tissue. Simultaneous cartilage and subchondral bone regeneration were achieved in vivo by using the tri-layered integrated scaffold. More importantly, the inclusion of the S layer could impart the regenerated cartilage with a more lubricating and wear-resistant surface. These findings suggest that the bioinspired construct mimicking the spatial variations of native osteochondral tissue might serve as a promising candidate to enhance osteochondral regeneration.

Keywords: Bioinspired; Electrohydrodynamic; Layer-specific induction; Melt electrowriting; Osteochondral regeneration; Superficial zone cartilage.

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Bioinspired stratified electrowritten fiber-reinforced hydrogel constructs with layer-specific induction capacity for functional osteochondral regeneration

Affiliations

Bioinspired stratified electrowritten fiber-reinforced hydrogel constructs with layer-specific induction capacity for functional osteochondral regeneration

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