BMHP1-Derived Self-Assembling Peptides: Hierarchically Assembled Structures with Self-Healing Propensity and Potential for Tissue Engineering Applications

Abstract

Self-assembling peptides (SAPs) are rapidly gaining interest as bioinspired scaffolds for cell culture and regenerative medicine applications. Bone Marrow Homing Peptide 1 (BMHP1) functional motif (PFSSTKT) was previously demonstrated to stimulate neural stem cell (NSC) viability and differentiation when linked to SAPs. We here describe a novel ensemble of SAPs, developed from the BMHP1 (BMHP1-SAPs), that spontaneously assemble into tabular fibers, twisted ribbons, tubes and hierarchical self-assembled sheets: organized structures in the nano- and microscale. Thirty-two sequences were designed and evaluated, including biotinylated and unbiotinylated sequences, as well as a hybrid peptide-peptoid sequence. Via X-ray diffraction (XRD), CD, and FTIR experiments we demonstrated that all of the BMHP1-SAPs share similarly organized secondary structures, that is, β-sheets and β-turns, despite their heterogeneous nanostructure morphology, scaffold stiffness, and effect over NSC differentiation and survival. Notably, we demonstrated the self-healing propensity of most of the tested BMHP1-SAPs, enlarging the set of potential applications of these novel SAPs. In in vitro cell culture experiments, we showed that some of these 10-mer peptides foster adhesion, differentiation, and proliferation of human NSCs. RGD-functionalized and hybrid peptide-peptoid self-assembling sequences also opened the door to BMHP1-SAP functionalization with further bioactive motifs, essential to tailor new scaffolds for specific applications. In in vivo experiments we verified a negligible reaction of the host nervous tissue to the injected and assembled BMHP1-SAP. This work will pave the way to the development of novel SAP sequences that may be useful for material science and regenerative medicine applications.

Insight on stem cell preconditioning and instructive biomaterials to enhance cell adhesion, retention, and engraftment for tissue repair

“…Self-assembling peptides. Self-assembling peptides (SAPs) are also attractive candidates as cell carriers and have been reported to enhance the survival and differentiation of transplanted cells [248][249][250][251][252][253]. SAPs consist of alternating hydrophilic and hydrophobic residues and form nanofibers at physiological pH or salt concentrations.…”

The Powerful Functions of Peptide-Based Bioactive Matrices for Regenerative Medicine

“…19 Scaffold design pertaining to control over biological signal presentation, 62 nanostructure 44 and mechanical properties 51 have also been shown to influence neuronal adhesion, differentiation, neurite growth and directional guidance in a culture environment. 29,55 For example, a PA nanofiber scaffold presenting the laminin-derived epitope IKVAV was shown to selectively induce the differentiation of the neural stem cells into neurons (Fig.…”

Self‐Assembling Peptides as Cell‐Interactive Scaffolds

“…Variations of bone marrow homing peptide 1 (BMHP1) appended to RAD16-I were later systematically studied for their effect on self-assembly and biomechanical properties. [64] It was discovered that a majority of the peptides demonstrated self-healing capability, allowing them to recover their stiffness after rupture. In addition to promoting neural stem cell proliferation and differentiation in vitro, the peptide hydrogels showed good short-term in vivo biocompatibility when injected into the spinal cord of rats [64] and were later shown to amerliorate the locomotor recovery of rats.…”

“…[64] It was discovered that a majority of the peptides demonstrated self-healing capability, allowing them to recover their stiffness after rupture. In addition to promoting neural stem cell proliferation and differentiation in vitro, the peptide hydrogels showed good short-term in vivo biocompatibility when injected into the spinal cord of rats [64] and were later shown to amerliorate the locomotor recovery of rats. [40] Following these studies, IKVAV was also appended to RAD16-I to improve rat neural stem cell proliferation and migration into the nanofiber matrix.…”