title: Surface-Functionalized Silk Fibroin Films as a Platform To Guide Neuron-like Differentiation of Human Mesenchymal Stem Cells.
abstract: Surface interactions at the biomaterial-cellular interface determine the proliferation and differentiation of stem cells. Manipulating such interactions through the surface chemistry of scaffolds renders control over directed stem cell differentiation into the cell lineage of interest. This approach is of central importance for stem cell-based tissue engineering and regenerative therapy applications. In the present study, silk fibroin films (SFFs) decorated with integrin-binding laminin peptide motifs (YIGSR and GYIGSR) were prepared and employed for in vitro adult stem cell-based neural tissue engineering applications. Functionalization of SFFs with short peptides showcased the peptide sequence and nature of functionalization-dependent differentiation of bone marrow-derived human mesenchymal stem cells (hMSCs). Intriguingly, covalently functionalized SFFs with GYIGSR hexapeptide (CL2-SFF) supported hMSC proliferation and maintenance in an undifferentiated pluripotent state and directed the differentiation of hMSCs into neuron-like cells in the presence of a biochemical cue, on-demand. The observed morphological changes were further corroborated by the up-regulation of neuronal-specific marker gene expression (MAP2, TUBB3, NEFL), confirmed through semiquantitative reverse-transcription polymerase chain reaction (RT-PCR) analysis. The enhanced proliferation and on-demand directed differentiation of adult stem cells (hMSCs) by the use of an economically viable short recognition peptide (GYIGSR), as opposed to the integrin recognition protein laminin, establishes the potential of SFFs for neural tissue engineering and regenerative therapy applications.
authors: Bioorganic Chemistry Laboratory, New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research , Jakkur, Bengaluru 560064, Karnataka, India.
authors: Shivaprasad
authors: S
authors: Manchineella
authors: Laboratory for Biomaterials, Materials Research Centre, Indian Institute of Science , Bengaluru 560012, Karnataka, India.
authors: Greeshma
authors: G
authors: Thrivikraman
authors: Laboratory for Biomaterials, Materials Research Centre, Indian Institute of Science , Bengaluru 560012, Karnataka, India.
authors: Bikramjit
authors: B
authors: Basu
authors: Bioorganic Chemistry Laboratory, New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research , Jakkur, Bengaluru 560064, Karnataka, India.
authors: T
authors: T
authors: Govindaraju
mesh_terms: D002454:Cell Differentiation; D049109:Cell Proliferation; D005349:Fibroins; D006801:Humans; D059630:Mesenchymal Stem Cells; D009474:Neurons; D047011:Silk; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D047011:Silk; D005349:Fibroins
keywords: biomaterials; laminin peptide; neuron-like stem cells; silk fibroin; surface functionalization; tissue engineering; transdifferentiation