Discovery of peptide domains with unique intermolecular interactions is essential for engineering peptide-based materials. Rather than attempting a brute-force approach, we instead identify a previously unexplored strategy for discovery and study of intermolecular interactions: “co-assembly of oppositely charged peptide” (CoOP), a framework that “encourages” peptide assembly by mixing two oppositely charged hexapeptides. We used an integrated computational and experimental approach, probed the free energy of association and probability of amino acid contacts during co-assembly with atomic-resolution simulations, and correlated them to the physical properties of the aggregates. We introduce CoOP with three examples: dialanine, ditryptophan, and diisoleucine. Our results indicated that the opposite charges initiate the assembly, and the subsequent stability is enhanced by the presence of an undisturbed hydrophobic core. CoOP represents a unique, simple, and elegant framework that can be used to identify the structure-property relationships of self-assembling peptide-based materials.
Infrapatellar fat pad is a densely vascularized and innervated extrasynovial tissue that fills the anterior knee compartment. It plays a role in knee biomechanics as well as constitutes a source of stem cells for regeneration after knee injury. Infrapatellar fat pad-derived stem cells (IPFP-ASCs) possess enhanced and age-independent differentiation capacity as compared to other stem cells, which makes them a very promising candidate in stem cell-based regenerative therapy. The aims of this review are to outline the latest advances and potential trends in using IPFP-ASCs and to emphasize the advantages over other sources of stem cells for applications in orthopedic surgery.
Peptide amphiphiles (PAs) self-assemble into supramolecular nanofiber gels that provide a suitable environment for encapsulation of both hydrophobic and hydrophilic molecules. The PA gels have significant advantages for controlled delivery applications due to their high capacity to retain water, biocompatibility, and biodegradability. In this study, we demonstrate injectable supramolecular PA nanofiber gels for drug delivery applications. Doxorubicin (Dox), as a widely used chemotherapeutic drug for breast cancer treatment, was encapsulated within the PA gels prepared at different concentrations. Physical and chemical properties of the gels were characterized, and slow release of the Dox molecules through the supramolecular PA nanofiber gels was studied. In addition, the diffusion constants of the drug molecules within the PA nanofiber gels were estimated using fluorescence recovery after the photobleaching (FRAP) method. The PA nanofiber gels did not show any cytotoxicity and the encapsulation strategy enhanced the activity of drug molecules on cellular viability through prolonged release compared to direct administration under in vitro conditions. Moreover, the local in vivo injection of the Dox encapsulated PA nanofiber gels (Dox/PA) to the tumor site demonstrated the lowest tumor growth rate compared to the direct Dox injection and increased the apoptotic cells within the tumor tissue for local drug release through the PA nanofiber gels under in vivo conditions.
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