期刊
BIOACTIVE MATERIALS
卷 15, 期 -, 页码 316-329出版社
KEAI PUBLISHING LTD
DOI: 10.1016/j.bioactmat.2021.12.015
关键词
Endogenous TGE beta 1; Injectable alkaline hydrogel; Cell homing; Pulp-dentin complex; In situ tissue regeneration
资金
- National Natural Science Foundation of China [81,700953]
- W. National Natural Science Foundation of China [81870753, R01DE025643, R01DE023112, R01AR065023, R01DE025969, R01DE026297]
This study developed a biomaterial-based strategy to activate endogenous TGF beta 1 under alkaline conditions for effective in situ tissue regeneration. The use of an injectable hydrogel allowed for controlled activation of TGF beta 1 and resulted in significant tissue regeneration in in vivo experiments.
Utilization of the body's regenerative potential for tissue repair is known as in situ tissue regeneration. However, the use of exogenous growth factors requires delicate control of the dose and delivery strategies and may be accompanied by safety, efficacy and cost concerns. In this study, we developed, for the first time, a biomaterial-based strategy to activate endogenous transforming growth factor beta 1 (TGF beta 1) under alkaline conditions for effective in situ tissue regeneration. We demonstrated that alkaline-activated TGF beta 1 from blood serum, bone marrow fluids and soaking solutions of meniscus and tooth dentin was capable of increasing cell recruitment and early differentiation, implying its broad practicability. Furthermore, we engineered an injectable hydrogel (MS-Gel) consisting of gelatin microspheres for loading strong alkaline substances and a modified gelatin matrix for hydrogel click crosslinking. In vitro models showed that alkaline MS-Gel controllably and sustainably activated endogenous TGF beta 1 from tooth dentin for robust bone marrow stem cell migration. More importantly, infusion of in vivo porcine prepared root canals with alkaline MS-Gel promoted significant pulp-dentin regeneration with neurovascular stroma and mineralized tissue by endogenous proliferative cells. Therefore, this work offers a new bench-to-beside translation strategy using biomaterial-activated endogenous biomolecules to achieve in situ tissue regeneration without the need for cell or protein delivery.
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