Multi-site enhancement of osteogenesis: peptide-functionalized GelMA hydrogels with three-dimensional cultures of human dental pulp stem cells

Author:

Liang Leyi1,Wang Shuze1,Zhang Xiyue1,Yan Tao2,Pan Xiyun1,Gao Yuzhong3,Zhang Xing4,Wang Qiang1,Qu Liu1

Affiliation:

1. Liaoning Provincial Key Laboratory of Oral Diseases, School and Hospital of Stomatology, China Medical University , Shenyang, Liaoning 110001, China

2. Department of Orthopedics and Sports Medicine and Joint Surgery, The People's Hospital of China Medical University , Shenyang, Liaoning 110016, China

3. Department of Orthopedics, The First Affiliated Hospital of Jinzhou Medical University , Jinzhou, Liaoning 121001, China

4. School of Materials Science and Engineering, University of Science and Technology of China , Hefei, Anhui 230026, China

Abstract

Abstract Human dental pulp stem cells (hDPSCs) have demonstrated greater proliferation and osteogenic differentiation potential in certain studies compared to other types of mesenchymal stem cells, making them a promising option for treating craniomaxillofacial bone defects. However, due to low extracting concentration and long amplifying cycles, their access is limited and utilization rates are low. To solve these issues, the principle of bone-forming peptide-1 (BFP1) in situ chemotaxis was utilized for the osteogenic differentiation of hDPSCs to achieve simultaneous and synergistic osteogenesis at multiple sites. BFP1-functionalized gelatin methacryloyl hydrogel provided a 3D culture microenvironment for stem cells. The experimental results showed that the 3D composite hydrogel scaffold constructed in this study increased the cell spread area by four times compared with the conventional GelMA scaffold. Furthermore, the problems of high stem cell dosage and low rate of utilization were alleviated by orchestrating the programmed proliferation and osteogenic differentiation of hDPSCs. In vivo, high-quality repair of critical bone defects was achieved using hDPSCs extracted from a single tooth, and multiple ‘bone island’-like structures were successfully observed that rapidly induced robust bone regeneration. In conclusion, this study suggests that this kind of convenient, low-cost, island-like osteogenesis strategy involving a low dose of hDPSCs has great potential for repairing craniomaxillofacial critical-sized bone defects.

Funder

Liaoning Provincial Natural Science Foundation of China

Central Guidance Funding for Local Scientific and Technological Development in Liaoning

Publisher

Oxford University Press (OUP)

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