3D bioprinting of ultrashort self-assembling peptides to engineer scaffolds with different matrix stiffness for chondrogenesis

Abstract

Articular cartilage is a non-vascularized and poorly cellularized tissue with a low self-repair capacity. Therefore, damage to this tissue due to trauma or degenerative joint diseases such as osteoarthritis needs a high-end medical intervention. However, such interventions are costly, have limited healing capacity, and could impair patients’ quality of life. In this regard, tissue engineering and three-dimensional (3D) bioprinting hold great potential. However, identifying suitable bioinks that are biocompatible, with the desired mechanical stiffness, and can be used under physiological conditions is still a challenge. In this study, we developed two tetrameric self-assembling ultrashort peptide bioinks that are chemically well-defined and can spontaneously form nanofibrous hydrogels under physiological conditions. The printability of the two ultrashort peptides was demonstrated; different shape constructs were printed with high shape fidelity and stability. Furthermore, the developed ultrashort peptide bioinks gave rise to constructs with different mechanical properties that could be used to guide stem cell differentiation toward specific lineages. Both ultrashort peptide bioinks demonstrated high biocompatibility and supported the chondrogenic differentiation of human mesenchymal stem cells. Additionally, the gene expression analysis of differentiated stem cells with the ultrashort peptide bioinks revealed articular cartilage extracellular matrix formation preference. Based on the different mechanical stiffness of the two ultrashort peptide bioinks, they can be used to fabricate cartilage tissue with different cartilaginous zones, including the articular and calcified cartilage zones, which are essential for engineered tissue integration.

Cysteine Redox Chemistry in Peptide Self-Assembly to Modulate Hydrogelation

“…In this manner, through self-assembly, nanofibrils can arise that entangle in hydrogel matrices [ 35 , 36 ]. This approach, which originally featured long peptides [ 37 , 38 ], has also been successfully applied to gradually shorter sequences, which have the advantage of lower costs and easier preparation [ 39 , 40 , 41 , 42 , 43 , 44 ]. Alternatively, inclusion of D-amino acids into heterochiral sequences can yield hydrogels from hydrophobic amino acids, so that the polar surface is composed of the peptide backbone, and the apolar surface is composed of the sidechains [ 45 , 46 , 47 ].…”

Clinical Relevance of Mesenchymal Stromal Cells from Various Sources: Insights into Transcriptome Analysis for Identifying Inherent Potential

“…Therefore, the employment of 3D culture, which closely mimics the native conditions, could be considered an alternative strategy to maintain the therapeutic potential of MSCs. Alternatively, 3D cultures of MSCs could be viewed as a route of cell administration, particularly if they support MSCs' proliferation and differentiation [130,131].…”

Selectively Positioned Catechol Moiety Supports Ultrashort Self-Assembling Peptide Hydrogel Adhesion for Coral Restoration

“…Soft-solid hydrogels made from rationally designed ultrashort self-assembling peptides (USPs) are synthetic in nature and are characterized by high water retention, low immunogenicity, high biocompatibility, tunable biomolecular and biophysical properties, and antibacterial properties. − Moreover, in our previous work, we validated their potential for wound healing, skin grafting, neuronal growth, osteogenesis, and three-dimensional (3D) bioprinting. − …”