title: 3D-Printed Atsttrin-Incorporated Alginate/Hydroxyapatite Scaffold Promotes Bone Defect Regeneration with TNF/TNFR Signaling Involvement.
abstract: High expression levels of pro-inflammatory tumor necrosis factor (TNF)-α within bone defects can decelerate and impair bone regeneration. However, there are few available bone scaffolds with anti-inflammatory function. The progranulin (PGRN)-derived engineered protein, Atsttrin, is known to exert antagonistic effects on the TNF-α function. Hence, this study investigates whether 3D-printed Atsttrin-incorporated alginate(Alg)/hydroxyapatite(nHAp) scaffolds can facilitate bone healing through affecting the TNF/TNFR signaling. A 3D bioprinting system is used to fabricate Atsttrin-Alg/nHAp composite scaffolds, and the Atsttrin release from this scaffold is characterized, followed by evaluation of its efficacy on bone regeneration both in vitro and in vivo. The 3D-printed Atsttrin-Alg/nHAp scaffold exhibits a precisely defined structure, can sustain Atsttrin release for at least 5 days, has negligible cytotoxicity, and supports cell adhesion. Atsttrin can also attenuate the suppressive effects of TNF-α on BMP-2-induced osteoblastic differentiation in vitro. The 3D-printed Atsttrin-Alg/nHAp scaffold significantly reduces the number of TNF-α positive cells within wound sites, 7 days after post-calvarial defect surgery. Additionally, histological staining and X-ray scanning results also show that the 3D-printed Atsttrin-Alg/nHAp scaffold enhances the regeneration of mice calvarial bone defects. These findings thus demonstrate that the precise structure and anti-inflammatory properties of 3D-printed Atsttrin-Alg/nHAp scaffolds may promote bone defect repair.
authors.affiliation: Center for Stem Cell and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, P. R. China.|Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, P. R. China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Center for Stem Cell and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, P. R. China.|Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, P. R. China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Xia
authors.affiliation: Center for Stem Cell and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, P. R. China.|Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Center for Stem Cell and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, P. R. China.|Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, P. R. China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Division of hematology and oncology, Shenzhen Children's Hospital, Shenzhen, P. R. China.
authors.forename: Feiqiu
authors.initials: F
authors.lastname: Wen
authors.affiliation: Division of hematology and oncology, Shenzhen Children's Hospital, Shenzhen, P. R. China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Chen
authors.affiliation: Center for Stem Cell and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, P. R. China.|Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, P. R. China.
authors.forename: Shufang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Biosystems Science & Engineering, ETH-Zurich, Mattenstrasse 26, Basel, Switzerland.
authors.forename: Boon Chin
authors.initials: BC
authors.lastname: Heng
authors.affiliation: The State Key Lab of Fluid Power Transmission and Control, School of Mechanical Engineering, Zhejiang University, Hangzhou, P. R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: He
authors.affiliation: Center for Stem Cell and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, P. R. China.|Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, P. R. China.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Ouyang
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D001847:Bone Diseases / Q000000981:diagnostic imaging / Q000473:pathology; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D001861:Bone Regeneration / Q000187:drug effects*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000473:pathology; D018929:Cell Culture Techniques; D004195:Disease Models, Animal; D017886:Durapatite / Q000737:chemistry*; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010012:Osteogenesis / Q000187:drug effects; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D054457:Tissue Scaffolds; D014057:Tomography, X-Ray Computed; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D000464:Alginates; C557987:Atsttrin fusion protein; D055396:Bone Morphogenetic Protein 2; D006603:Hexuronic Acids; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D020723:Glucuronic Acid; D017886:Durapatite
keywords: Atsttrin; TNF-α; bioprints; bone regeneration; scaffolds