Recapitulation of growth factor-enriched microenvironment via BMP receptor activating hydrogel

Exposure to a growth factor abundant milieu has remarkable regenerative and rejuvenating effects on organ diseases, tissue damage, and regeneration, including skeletal system defects and bone regeneration. Although the introduction of candidate growth factors into relevant fields has been reported,...

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Main Authors: Qinghao Zhang, Yuanda Liu, Jie Li, Jing Wang, Changsheng Liu
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2023-02-01
Series:Bioactive Materials
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X2200278X
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author Qinghao Zhang
Yuanda Liu
Jie Li
Jing Wang
Changsheng Liu
author_facet Qinghao Zhang
Yuanda Liu
Jie Li
Jing Wang
Changsheng Liu
author_sort Qinghao Zhang
collection DOAJ
description Exposure to a growth factor abundant milieu has remarkable regenerative and rejuvenating effects on organ diseases, tissue damage, and regeneration, including skeletal system defects and bone regeneration. Although the introduction of candidate growth factors into relevant fields has been reported, their regenerative effects remain unsatisfactory, mainly because of the experimental challenges with limited types of growth factors, elusive dosage adjustment, and asynchronous stem cell activation with cytokine secretion. Here, an innovative hydrogel recapitulating a growth factor-enriched microenvironment (GEM) for regenerative advantage, is reported. This sulfated hydrogel includes bone morphogenetic protein-2 (BMP-2), an essential growth factor in osteogenesis, to direct mesenchymal stem cell (MSC) differentiation, stimulate cell proliferation, and improve bone formation. The semi-synthetic hydrogel, sulfonated gelatin (S-Gelatin), can amplify BMP-2 signaling in mouse MSCs by enhancing the binding between BMP-2 and BMP-2 type II receptors (BMPR2), which are located on MSC nuclei and activated by the hydrogel. Importantly, the dramatically improved cytokine secretion of MSCs throughout regeneration confirms the growth factor-acquiring potential of S-Gelatin/rhBMP-2 hydrogel, leading to the vascularization enhancement. These findings provide a new strategy to achieve an in situ GEM and accelerated bone regeneration by amplifying the regenerative capacity of rhBMP-2 and capturing endogenous growth factors.
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spelling doaj.art-0d416b415d9b46878caf93feea51a28a2022-12-22T04:34:23ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2023-02-0120638650Recapitulation of growth factor-enriched microenvironment via BMP receptor activating hydrogelQinghao Zhang0Yuanda Liu1Jie Li2Jing Wang3Changsheng Liu4Material Science and Engineering School, East China University of Science and Technology, Shanghai, 200237, PR China; Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, PR China; Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, PR China; Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, Meilong Road 130, Shanghai, 200237, PR China; Corresponding author. Material Science and Engineering School, East China University of Science and Technology, Shanghai, 200237, PR China.Material Science and Engineering School, East China University of Science and Technology, Shanghai, 200237, PR China; Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, PR China; Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, PR China; Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, Meilong Road 130, Shanghai, 200237, PR ChinaMaterial Science and Engineering School, East China University of Science and Technology, Shanghai, 200237, PR China; Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, PR China; Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, PR China; Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, Meilong Road 130, Shanghai, 200237, PR ChinaMaterial Science and Engineering School, East China University of Science and Technology, Shanghai, 200237, PR China; Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, PR China; Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, PR China; The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, PR China; Corresponding author. Material Science and Engineering School, East China University of Science and Technology, Shanghai, 200237, PR China.Material Science and Engineering School, East China University of Science and Technology, Shanghai, 200237, PR China; Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, PR China; Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, PR China; Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, Meilong Road 130, Shanghai, 200237, PR China; Corresponding author. Material Science and Engineering School, East China University of Science and Technology, Shanghai, 200237, PR China.Exposure to a growth factor abundant milieu has remarkable regenerative and rejuvenating effects on organ diseases, tissue damage, and regeneration, including skeletal system defects and bone regeneration. Although the introduction of candidate growth factors into relevant fields has been reported, their regenerative effects remain unsatisfactory, mainly because of the experimental challenges with limited types of growth factors, elusive dosage adjustment, and asynchronous stem cell activation with cytokine secretion. Here, an innovative hydrogel recapitulating a growth factor-enriched microenvironment (GEM) for regenerative advantage, is reported. This sulfated hydrogel includes bone morphogenetic protein-2 (BMP-2), an essential growth factor in osteogenesis, to direct mesenchymal stem cell (MSC) differentiation, stimulate cell proliferation, and improve bone formation. The semi-synthetic hydrogel, sulfonated gelatin (S-Gelatin), can amplify BMP-2 signaling in mouse MSCs by enhancing the binding between BMP-2 and BMP-2 type II receptors (BMPR2), which are located on MSC nuclei and activated by the hydrogel. Importantly, the dramatically improved cytokine secretion of MSCs throughout regeneration confirms the growth factor-acquiring potential of S-Gelatin/rhBMP-2 hydrogel, leading to the vascularization enhancement. These findings provide a new strategy to achieve an in situ GEM and accelerated bone regeneration by amplifying the regenerative capacity of rhBMP-2 and capturing endogenous growth factors.http://www.sciencedirect.com/science/article/pii/S2452199X2200278XBMP-2Sulfonated acidsBMP receptor ActivationEndogenous growth factor acquisitionBone regeneration
spellingShingle Qinghao Zhang
Yuanda Liu
Jie Li
Jing Wang
Changsheng Liu
Recapitulation of growth factor-enriched microenvironment via BMP receptor activating hydrogel
Bioactive Materials
BMP-2
Sulfonated acids
BMP receptor Activation
Endogenous growth factor acquisition
Bone regeneration
title Recapitulation of growth factor-enriched microenvironment via BMP receptor activating hydrogel
title_full Recapitulation of growth factor-enriched microenvironment via BMP receptor activating hydrogel
title_fullStr Recapitulation of growth factor-enriched microenvironment via BMP receptor activating hydrogel
title_full_unstemmed Recapitulation of growth factor-enriched microenvironment via BMP receptor activating hydrogel
title_short Recapitulation of growth factor-enriched microenvironment via BMP receptor activating hydrogel
title_sort recapitulation of growth factor enriched microenvironment via bmp receptor activating hydrogel
topic BMP-2
Sulfonated acids
BMP receptor Activation
Endogenous growth factor acquisition
Bone regeneration
url http://www.sciencedirect.com/science/article/pii/S2452199X2200278X
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