Scale/Topography of Substrates Surface Resembling Extracellular Matrix for Tissue Engineering

Abstract

Biomaterial matrices are being developed that mimic the key characteristics of the extracellular matrix, including presenting adhesion sites and displaying growth factors in the context of a viscoelastic hydrogel. This review focuses on two classes of materials: those that are derived from naturally occurring molecules and those that recapitulate key motifs of biomolecules within biologically active synthetic materials. We also discussed some of the most significant biological features of the ECM, and several engineering methods currently being implemented to design and tune synthetic scaffolds to mimic these features. Understanding the cell-protein-material interaction is fundamental for developing more powerful tools in tissue engineering and regenerative medicine strategies. The design of model substrates including the presence of well-defined properties (chemistry, topography, stiffness) and even the gradient of these properties in three dimensional environments must lead in the near future to learn more about the specific roles of protein adsorption and the very dynamic process related to the cell fate of synthetic substrates: cell adhesion, matrix reorganisation, deposition and degradation at the cell-material interface. These materials will open new doors to biosurgical therapeutics in tissue engineering and regenerative medicine.

Advancing biomaterials of human origin for tissue engineering

“…Whereas composite biomaterials from the same class will generate a certain degree of regulation, mixing biomaterials from multiple classes may confer a greater level of control over the overall material properties for cell guidance. For example, hybrid hydrogel scaffolds synthesized from selected biopolymers may provide opportunities to closely mimic the key characteristics of the native ECM, including by displaying adhesion sites and presenting growth factors, which not only induces reparative cells but also triggers and governs specific events at the cellular and tissue levels [48,88]. In particular, the addition of natural components, with their natural ratios, into synthetic polymers, followed by the incorporation of biochemical and biophysical cues, mirroring the chemistry as well as the nanofibrous network of the native matrix, has emerged as a leading strategy in scaffolding design [52,89].…”

“…Biomimetic hydrogels formed by self-assembled biopolymer networks such as silk, keratin elastin, resilin and periodate oxidized alginate and gelatin display close chemical, structural and mechanical similarities with the native ECM and have therefore been widely used as artificial cell niches with tunable properties that favor cell functions similar to the events occurring in natural extracellular microenvironments [64,317,387,469,673,674]. In addition, these hydrogels, which are either derived from naturally occurring molecules or are synthetic polymers that recapitulate key motifs of biomolecules, typically have a highly interconnected porous network, good biological compatibility and maybe degraded by proteolytic enzymes in the body, holding great promise for various biomedical applications [88,675]. However, the reproducibility of cell constructs often remains complicated because of batch-to-batch variation and the sensitivity of cells (especially progenitor or stem cells) to these differences.…”

Graphene-based nanomaterials: biological and medical applications and toxicity

“…One of the most relevant principles in tissue engineering involves the development of bioactive degradable substrates, known as scaffolds, with biocompatible surfaces and favorable mechanical properties suitable for cell culture, which not only allow cellular attachment, proliferation, differentiation, but also support for new tissue formation [66]. To achieve this purpose, scaffolds must possess specific properties for tissue reconstruction and biological response.…”

“…To achieve this purpose, scaffolds must possess specific properties for tissue reconstruction and biological response. The main characteristics include: biodegradability: to avoid the necessity of surgical removal, the scaffolds must be made from materials with controlled biodegradability or bioresorbability by the surrounding tissues; high porosity: to facilitate cell adhesion and diffusion, the scaffold must have high porosity and suitable interconnecting pore size to favor tissue integration and vascularization; surface: surface chemical modification to favor cell attachment, differentiation and proliferation; mechanical properties; biocompatibility: not induce adverse response and pliability: able to be produced into a variety of shapes and sizes [66].…”

“…This system of protection in the brain acts against toxic and infectious agents while maintaining the ionic and volumetric environments; however, it also creates an obstacle for effective systemic drug delivery to the brain [152]. Under the physiological conditions, circulating molecules can only gain access to the brain via diffusion (paracellular or transcellular) or specific receptor-mediated or vesicular mechanisms (adsorptive transcytosis) [66,153].…”