Chirality and morphology are essential factors for protein function and interactions with other biomacromolecules. Extracellular matrix (ECM) proteins are also similar to other proteins in this sense; however, the complexity of the natural ECM makes it difficult to study these factors at the cellular level. The synthetic peptide nanomaterials harbor great promise in mimicking specific ECM molecules as model systems. In this work, we demonstrate that mechanosensory responses of stem cells are directly regulated by the chirality and morphology of ECM-mimetic peptide nanofibers with strictly controlled characteristics. Structural signals presented on l-amino acid containing cylindrical nanofibers (l-VV) favored the formation of integrin β1-based focal adhesion complexes, which increased the osteogenic potential of stem cells through the activation of nuclear YAP. On the other hand, twisted ribbon-like nanofibers (l-FF and d-FF) guided the cells into round shapes and decreased the formation of focal adhesion complexes, which resulted in the confinement of YAP proteins in the cytosol and a corresponding decrease in osteogenic potential. Interestingly, the d-form of twisted-ribbon like nanofibers (d-FF) increased the chondrogenic potential of stem cells more than their l-form (l-FF). Our results provide new insights into the importance and relevance of morphology and chirality of nanomaterials in their interactions with cells and reveal that precise control over the chemical and physical properties of nanostructures can affect stem cell fate even without the incorporation of specific epitopes.
Lower back pain (LBP) is a prevalent spinal symptom at the lumbar region of the spine, which severely effects quality of life and constitutes the number one cause of occupational disability. Degeneration of the intervertebral disc (IVD) is one of the well-known causes contributing to the LBP. Therapeutic biomaterials inducing IVD regeneration are promising candidates for IVD degeneration treatments. Here, we demonstrate a collagen peptide presenting nanofiber scaffold to mimic the structure and function of the natural extracellular matrix of the tissue for IVD regeneration. The collagen peptide presenting nanofiber was designed by using a Pro-Hyp-Gly (POG) peptide sequence on a self-assembling peptide amphiphile molecule, which assembled into nanofibers forming scaffolds. Injection of collagen peptide presenting peptide nanofiber scaffold into the degenerated rabbit IVDs induced more glycosaminoglycan and collagen deposition compared to controls. Functional recovery of the tissue was evaluated by degeneration index score, where the bioactive scaffold was shown to provide functional recovery of the IVD degeneration. These results showed that the collagen peptide presenting nanofiber scaffold can prevent the progression of IVD degeneration and provide further functional recovery of the tissue.
Sports, heavy lifting and other strength-intensive tasks are ubiquitous in modern life and likely to cause acute skeletal muscle injury. Speeding up regeneration of skeletal muscle injuries would not only shorten the duration of recovery for the patient, but also support the general health and functionality of the repaired muscle tissue. In this work, we designed and synthesized a laminin-mimetic nanosystem to enhance muscle regeneration. We tested its activity in a rat tibialis anterior muscle by injecting the bioactive nanosystem. The evaluation of the regeneration and differentiation capacity of skeletal muscle suggested that the laminin-mimetic nanosystem enhances skeletal muscle regeneration and provides a suitable platform that is highly promising for the regeneration of acute muscle injuries. This work demonstrates for the first time that laminin-mimetic self-assembled peptide nanosystems facilitate myogenic differentiation in vivo without the need for additional treatment.
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