4.8 Article

A sericin/ graphene oxide composite scaffold as a biomimetic extracellular matrix for structural and functional repair of calvarial bone

Journal

THERANOSTICS
Volume 10, Issue 2, Pages 741-756

Publisher

IVYSPRING INT PUBL
DOI: 10.7150/thno.39502

Keywords

Sericin; Graphene oxide; Bone regeneration; Bone marrow-derived mesenchymal stem cells; Migration and osteogenesis differentiation

Funding

  1. National Natural Science Foundation of China Programs [81873931, 81671904, 81773263, 81572866]
  2. International Science and Technology Corporation Program of Chinese Ministry of Science and Technology [S2014ZR0340]
  3. Science and Technology Program of Chinese Ministry of Education [113044A]
  4. Frontier Exploration Program of Huazhong University of Science and Technology [2015TS153]
  5. Natural Science Foundation Program of Hubei Province [2019CFB466, 2015CFA049]
  6. Graduates' Innovation Fund of Huazhong University of Science and Technology [2019ygscxcy069]
  7. Integrated Innovative Team for Major Human Diseases Program of Tongji Medical College, HUST
  8. Academic Medical Doctors Supporting Program of Tongji Medical College, HUST

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Bone defects affect millions of people worldwide each year, leading to severe disabilities. Biomimetic scaffolds mediated tissue regeneration represents a promising alternative for bone repair. However, the major problem associated with most currently clinical available artificial bone substitutes (scaffolds) is that they mainly possess filling function but lack of osteo-induction abilities. Therefore, development of biomaterials with osteo-induction property for effective bone regeneration is highly desired. Methods: We report the design and fabrication of a photo-crosslinked sericin methacryloyl (SerMA)/ graphene oxide (GO) hydrogel (SMH/GO) as a biomimetic scaffold for the functional repair of the bone. The mechanical strength, degradation and biocompatibility behavior of SMH/GO hydrogel were measured in vitro. The effect of SMH/GO hydrogel on BMSCs proliferation, migration, osteogenesis differentiation was assessed. After that, SMH/GO-2 was used as an artificial bone substitute for bone regeneration after calvarial defects and effect on bone repair was evaluated by histological, X-Ray and microCT analysis. Furthermore, the potential mechanism of SMH/GO hydrogel regulating BMSCs migration and differentiation was investigated by RNA sequencing. Results: This scaffold has good biocompatibility, cell adhesive property, proliferation- and migration-promoting effects, and osteogenic induction property. After being implanted in a rat calvarial defect model, this SMH/GO scaffold effectively promotes new bone regeneration and achieves structural and functional repair within 12 weeks by inducing autologous bone marrow-derived mesenchymal stem cells (BMSCs) differentiation. By utilizing cell-biological assays and RNA sequencing, we reveal its possible regeneration mechanisms: the SMH/GO hydrogel regulates BMSCs migration and osteo-differentiation via activating MAPK, TNF, and chemokine signaling for bone regeneration. Conclusion: Aiming to meet clinical demands and overcome current limitations of existing artificial bones, we have developed a new type of sericin/ graphene oxide composite scaffold and provided histological, functional, and molecular evidence demonstrating that it is capable of effectively repairing defective bones by inducing autologous BMSCs directional migration and osteogenic differentiation.

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