Chimeric Self-assembling Nanofiber Containing Bone Marrow Homing Peptide’s Motif Induces Motor Neuron Recovery in Animal Model of Chronic Spinal Cord Injury; an In Vitro and In Vivo Investigation

Abstract

To date, spinal cord injury (SCI) has remained an incurable disaster. The use of self-assembling peptide nanofiber containing bioactive motifs such as bone marrow homing peptide (BMHP1) as an injectable scaffold in spinal cord regeneration has been suggested. Human endometrial-derived stromal cells (hEnSCs) have been approved by the FDA for clinical application. In this regard, we were interested in investigating the role of BMHP1 in hEnSCs' neural differentiation in vitro and evaluating the supportive effects of this scaffold in rat model of chronic SCI. 1,1-Diphenyl-2-picryl-hydrazyl (DPPH), lactate dehydrogenase (LDH) release, 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay, real-time PCR, and immunocyotochemistry (ICC) were performed as a biocompatibility and neural differentiation evaluations on neuron-like hEnSC-derived cells encapsulated into nanofiber. Nanofiber was implanted into rats and followed by behavioral test, Nissl, luxol fast blue (LFB) staining and immunohistostaining (IHC). Results indicated that cell membrane of neuroblastoma cells were more sensitive than hEnSCs to concentration of proton and cell proliferation decreased with increase of concentration. This effect might be related to oxygen tension and elastic modules of scaffold. -BMHP1 nanofiber induced neural differentiation in hEnSC and decreased GFAP gene and protein as a marker of reactive astrocytes in vitro and in vivo. A reason for this finding might be related to the role of spacer number in induction of mechano-transduction signals. The presented study revealed the chimeric BMHP1 nanofiber induced higher axon regeneration and myelniation around the cavity and motor neuron function was encouraged to improve with less inflammatory response following SCI in rats. These effects were possibly due to nanostructured topography and mechano-transduction signals derived from hydrogel at low concentration.

Self-Assembling Peptide Nanofiber Containing Long Motif of Laminin Induces Neural Differentiation, Tubulin Polymerization, and Neurogenesis: In Vitro, Ex Vivo, and In Vivo Studies

“…That investigation showed that cell attachment of -BMHP nanofiber was higher than short laminin's motif. Our study also indicated that cell viability of encapsulated cells into -BMHP nanofiber was higher than long laminin's motif [36].…”

Regenerative Therapies for Spinal Cord Injury

“…The concept of biomaterials that can be injected and form a defined guidance architecture in situ is attractive; nevertheless, development of such biomaterials has posed a formidable challenge. Promising strategies to overcome this challenge include the use of scaffolds that are based on self-assembling fibers 56,95,124,180 or that are embedded with magnetically responsive microgels. 58 In an interesting study, poly(ethylene oxide-stat-propylene oxide) gels containing supermagnetic iron oxide nanorods were used to help the orientation of nerve extension parallel to the rods that were aligned by using an external magnetic field.…”

Designer D-form self-assembling peptide scaffolds promote the proliferation and migration of rat bone marrow-derived mesenchymal stem cells

“…This denotes that D-RADA16 and L-RADA16 are enantiomers. The β-sheet structure is essential for peptides in tissue engineering, as this structure has the ability of nanofiber formation and provides support to the cytoskeleton fiber (38). Previous studies have demonstrated that L-RADA16 can self-assemble into a stable β-sheet structure at physiologic conditions, forming interwoven nanofiber scaffolds that mimic the architecture of the ECM (34,39–41).…”