Designer Self‐Assembling Peptide Hydrogels to Engineer 3D Cell Microenvironments for Cell Constructs Formation and Precise Oncology Remodeling in Ovarian Cancer

Abstract

mouse intestinal stem cells and primary colorectal cancer cells can be propagated in vitro long term, [1] there is an urgent need to develop more physiologically relevant, efficient, and robust precise oncology models that closely recapitulate the genetic and morphological heterogeneous composition and mimic the arrangement pattern of cancer cells in the original tumor. [2] To our knowledge in biomedical research, hydrogel is the best tool to reconstruct precise oncology models in vitro, especially tumor organoid, which not only recapitulates in vivo biology and microenvironmental factors, but also at large extent allows side-by-side comparison to evaluate the translational potential of 3D model systems to the patients. [2a,3] Generally, hydrogels are mainly composed of hydrophilic polymeric scaffolds that absorb large amounts of water, so the hydrogel matrix better mimics elastic and viscoelastic properties in ECM and microscale topographies of cell matrices, which controls proper cell morphology, directs viable cell behaviors, and drives in vivo fundamental cell-cell or cell-ECM interactions. [4] To recapitulate pathophysiological features of human tumors and imitate various aspects of human tumorigenesis in vivo, hydrogels can provide a realistic platform to establish a useful bridge between in vitro assays and in vivo cell microenvironments. In current biomedical applications, there are many kinds of hydrogels to be developed to mimic the biological properties of ECM, such 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.

Self-assembling tetrameric peptides allow in situ 3D bioprinting under physiological conditions

“…[2][3][4] Moreover, due to their unique properties, selfassembling peptides had been used in a wide range of biomedical applications including drug delivery, anti-cancer treatment, wound healing and as antimicrobial agents. [5][6][7] While different bioink materials are commercially available for 3D cell culture as well as for 3D bioprinting applications, majority of these materials include steps that are harsh for viable cells such as crosslinking by UV-treatment or chemical polymerization to transform pre-polymeric viscous solutions into a stable scaffold. [8][9][10][11] During these processes, the printed cells might get damaged due to exposure to UV light or toxic chemicals.…”

Recent Progress in the Design and Application of Supramolecular Peptide Hydrogels in Cancer Therapy

“…[96] These properties are associated with cell differentiation and functions in particular tissues. [97,98] Therefore, it is critical to adjust the mechanical properties for the purposed biomedical applications. To quantify the mechanical strength of hydrogels, storage modulus G′ and loss modulus G″ are the most widely used parameters.…”

Conjugates of Chitosan and Calcium Alginate with Oligoproline and Oligohydroxyproline Derivatives for Potential Use in Regenerative Medicine

“…Therefore, derivatives derived from growth factors affecting endothelial cell proliferation, migration, viability and angiogenesis are also useful in medicine. In addition to peptides derived from proteins and polypeptides present in ECM, synthetic peptides belonging to the group of self-assembly peptides (SAPs) are also known, which are also increasingly used in regenerative medicine [85][86][87]. The described oligoproline/oligohydroxyproline derivatives, although belonging to the group of synthetic peptides are able to mimic the collagen spatial structure and positively affect endothelial cell line.…”