From Soft to Hard Biomimetic Materials: Tuning Micro/Nano-Architecture of Scaffolds for Tissue Regeneration

Abstract

Failure of tissues and organs resulting from degenerative diseases or trauma has caused huge economic and health concerns around the world. Tissue engineering represents the only possibility to revert this scenario owing to its potential to regenerate or replace damaged tissues and organs. In a regeneration strategy, biomaterials play a key role promoting new tissue formation by providing adequate space for cell accommodation and appropriate biochemical and biophysical cues to support cell proliferation and differentiation. Among other physical cues, the architectural features of the biomaterial as a kind of instructive stimuli can influence cellular behaviors and guide cells towards a specific tissue organization. Thus, the optimization of biomaterial micro/nano architecture, through different manufacturing techniques, is a crucial strategy for a successful regenerative therapy. Over the last decades, many micro/nanostructured biomaterials have been developed to mimic the defined structure of ECM of various soft and hard tissues. This review intends to provide an overview of the relevant studies on micro/nanostructured scaffolds created for soft and hard tissue regeneration and highlights their biological effects, with a particular focus on striated muscle, cartilage, and bone tissue engineering applications.

Keywords: architectural features; bone regeneration; cardiac muscular regeneration; cartilage regeneration; micro/nanostructured biomaterials; scaffolding strategies; tissue engineering; tissue regeneration.

Figure 1

The stiffness of living tissues. The biomechanical properties of a tissue in terms of stiffness (elastic modulus), measured in pascals (Pa), vary between organs and tissues. Soft tissues such as the brain exhibit low stiffness, whereas tissues exposed to high mechanical loading, such as bone, exhibit elastic moduli with a stiffness that is several orders of magnitude greater. Values of Young’s modulus were from ref. [14]. The figure was created using Servier Medical Art and 3d models of Microsoft 365.

Figure 2

The hierarchical structure of natural bone from macro to nanoscale. The schematic representation of the long bone structure is shown as an example. In the macroscopic view, bone cross-section can be divided into an external and an internal part. The bone external structure consists of compact cortical bone which is composed of densely packed cylindrical osteons. The internal cancellous bone has a porous trabecular structure. Osteons and trabeculae are made up of lamellae with different collagen fiber patterns. The collagen fibers (~1 µm) are composed of bundles of mineralized collagen fibrils (~100 nm), in which hydroxyapatite nanocrystals (nanoscale size) are deposited in the gaps between collagen molecules (tropocollagen triple helices). The figure was created using Servier Medical Art.

Figure 3

Schematic representation of micro/nanoscale surface patterns (Reprinted with permission from ref. [20] Copyright 2022, Elsevier and schematic representation of cell–nanotopography interactions. Adapted with permission from ref. [29] Copyright 2022 American Chemical Society.