Abstract
Designer self‐assembling peptides form the entangled nanofiber networks in hydrogels by ionic‐complementary self‐assembly. This type of hydrogel has realistic biological and physiochemical properties to serve as biomimetic extracellular matrix (ECM) for biomedical applications. The advantages and benefits are distinct from natural hydrogels and other synthetic or semisynthetic hydrogels. Designer peptides provide diverse alternatives of main building blocks to form various functional nanostructures. The entangled nanofiber networks permit essential compositional complexity and heterogeneity of engineering cell microenvironments in comparison with other hydrogels, which may reconstruct the tumor microenvironments (TMEs) in 3D cell cultures and tissue‐specific modeling in vitro. Either ovarian cancer progression or recurrence and relapse are involved in the multifaceted TMEs in addition to mesothelial cells, fibroblasts, endothelial cells, pericytes, immune cells, adipocytes, and the ECM. Based on the progress in common hydrogel products, this work focuses on the diverse designer self‐assembling peptide hydrogels for instructive cell constructs in tissue‐specific modeling and the precise oncology remodeling for ovarian cancer, which are issued by several research aspects in a 3D context. The advantages and significance of designer peptide hydrogels are discussed, and some common approaches and coming challenges are also addressed in current complex tumor diseases.
Highlights
Designer self-assembling peptides form the entangled nanofiber networks mouse intestinal stem cells and primary in hydrogels by ionic-complementary self-assembly
The hydrogelation is mediated in salt solutions by the desired triggering of intramolecular peptide folding within ≈30 min, which is a unique type of molecular self-assembly mechanism with concurrent fibril selfassembly and entanglement into matrix networks compared to other designer peptide hydrogels.[33a,108] When designed to be MAX8 peptide, that enables swifter folding and faster molecular self-assembly in monomer within 1 min and forms more rigid hydrogels, this kind of hydrogels is injectable, good biocompatible, customizable, and highly responsive to mechanical shear in biomedical applications.[109]
There are many 3D cell culture models reported in designer peptide hydrogels for basic cancer research (Table 2), few molecular-leveled peptide backbone decorations are identified to remodel tissue-specific tumor microenvironments (TMEs) in vitro involved in specific tissue or cell subtypes, that may be a challenging task in current matrix biology community.[64]
Summary
Molecular self-assembly is a popular and highly efficient strategy to form a large and well-organized structure to present compositional complexity and achieve most of the functionality for organisms.[16]. Based on the hydrophilic surface of molecular building blocks with alternating positively and negatively charged amino acid residues, the classical designer self-assembling peptides are termed as a type of Lego peptides with ionic-complementary properties. The alternate charge style in each modulus is following: modulus I, − + − + − + − +; modulus II, − − + + − − + +; modulus III, − − − + + +; and modulus IV, − − − − + + + +, which are alternated by 1, 2, 3, 4 and so on (Figure 1).[25] Designer self-assembling peptides studied so far have the charge orientation described above and show the reverse charge orientations and amino acid residue patterns that produce different molecular building blocks with the defined molecular self-assembly behaviors. Www.advancedscience.com is analogous to the circumstances found in the well-studied synthetic polymers in supramolecular chemistry This type of molecular self-assembly principle has paved the foundation of nanofiber architecture formation in designer self-assembling peptides, including the entangled nanofiber networks and the hydrogelation process in solution. Since a rational study of the effect produced for each component added to the scaffold (growth factor, polysaccharide or signaling peptide) can be carried out,[20] it is a good promise to achieve the generation biomaterials to preserve the native form of growth factor in all hydrogel volumes.[24,31] Concurrently, molecular self-assemblies in peptides and proteins are moving from modulating cellular functionality in 3D context to the predictive creation of new biomimetic nanomaterials by bioengineering strategies at the molecular or atomic levels.[29,32] All in all, based on bottom-up bioengineering strategies the predictive design and biomimetic capacity of designer self-assembling peptide hydrogels would enhance the development of more physiological and reliable 3D cell models and help the biomedical industry to develop better molecular or cellular therapy approaches in tissue engineering, regenerative medicine, cancer management, or other biomedical applications
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