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

Abstract

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.

<p>Applications of Graphene and Its Derivatives in Bone Repair: Advantages for Promoting Bone Formation and Providing Real-Time Detection, Challenges and Future Prospects</p>

“…Stem cells from different sources could be used as progenitor cells in the process of bone formation, so their recruitment and osteogenic differentiation were key factors for effective bone regeneration. GDs were proved to have the ability of osteogenic induction, [144][145][146][147][148][149][150][151][152] as shown in Table 4. In this subsection, the signaling pathways involved in GDs-induced bone regeneration were discussed, including which signaling pathways of osteogenic differentiation of stem cells from different sources were affected by GDs and the effect of GDsrelated parameters on the signaling pathway.…”

“…Firstly, when GDs were used alone and GDs were combined with other materials, the signaling pathways involved in GDs-induced bone regeneration were different, which might be due to the change of the surface charge and groups after GDs were introduced into the matrix. For example, Qi et al 144 prepared sericin methacryloyl/GO (SMH/GO) composite hydrogel as bone repair material by photo-crosslinking. The results of in vivo experiments showed that the hydrogel containing GO had a better bone regeneration effect, and the structure and function of rat skull defect model were repaired within 12 weeks.…”

NIR light-assisted phototherapies for bone-related diseases and bone tissue regeneration: A systematic review

“…In addition, carbon-based nanomaterials, such as GO and single-/multi-walled carbon nanotubes, offer great promise for cancer photothermal therapies because of their strong NIR light absorbance, excellent photothermal performance and satisfactory cytocompatibility 68 - 71 . It also has been reported that carbon-based nanomaterials can effectively improve bone regeneration by inducing the directional migration and osteogenic differentiation of BMSCs 72 , 73 . For example, GO‑modified biofunctional tricalcium silicate bone cement and TCP bone scaffolds have been fabricated for cancer therapy and bone tissue regeneration 59 , 71 .…”

Sericin microparticles enveloped with metal-organic networks as a pulmonary targeting delivery system for intra-tracheally treating metastatic lung cancer

“…Sericin is a natural protein extracted from silkworm cocoons. Due to its good biocompatibility, biodegradability, low-immunogenicity and natural cell adhesion [ 28 , 29 ], sericin has been widely used to develop tissue engineering scaffolds or nanocarriers for drug delivery [ [30] , [31] , [32] , [33] , [34] , [35] ], as well as the silk fibroin [ 36 , 37 ]. Hence, we proposed to prepare a pulmonary delivery system composed of (1) sericin microparticles (SMPs) as the core carrier, that can effectively encapsulate anticancer drug, and (2) tannic acid (TA) and ferric irons (Fe 3+ ) based metal-organic networks (MON) coating on SMPs ( Scheme 1 ).…”