Functional Scaffolds for Bone Tissue Regeneration: A Comprehensive Review of Materials, Methods, and Future Directions

Abstract

Bone tissue regeneration is a rapidly evolving field aimed at the development of biocompatible materials and devices, such as scaffolds, to treat diseased and damaged osseous tissue. Functional scaffolds maintain structural integrity and provide mechanical support at the defect site during the healing process, while simultaneously enabling or improving regeneration through amplified cellular cues between the scaffold and native tissues. Ample research on functionalization has been conducted to improve scaffold-host tissue interaction, including fabrication techniques, biomaterial selection, scaffold surface modifications, integration of bioactive molecular additives, and post-processing modifications. Each of these methods plays a crucial role in enabling scaffolds to not only support but actively participate in the healing and regeneration process in bone and joint surgery. This review provides a state-of-the-art, comprehensive overview of the functionalization of scaffold-based strategies used in tissue engineering, specifically for bone regeneration. Critical issues and obstacles are highlighted, applications and advances are described, and future directions are identified.

Keywords: 3D printing; bone tissue regeneration; functionalization; osseous defects; scaffolds.

Figure 1

Properties that an ideal scaffold should display for bone tissue engineering applications. Reprinted with permission from ref. [11]. Copyright 2017 Elsevier Ltd.

Figure 2

Representative schematics: (A) Bone. Image reprinted with permission from Rho et al. [36]. Copyright 1998, Elsevier Ltd. (B) Articular cartilage showing the variation in the anatomical structure at the macro-, micron- and sub-micron levels. Reprinted with permission from ref. [37]. Copyright 2016 Elsevier Ltd.

Figure 6

Schematic depicting adenosine receptor activation. Reprinted with permission from ref. [241]. Copyright 2019 Elsevier Ltd.

Figure 7

Representative schematic showing bottom-up and top-down strategies for tissue regeneration by using cell-laden scaffolds. Reprinted from ref. [262].

Figure 3

Visualization of various bioprinting techniques. Reprinted from ref. [159].

Figure 4

Scanning electron micrographs of scaffolds with different pore dimensions and porosities (A–C); at different magnifications (i–iii). Reprinted from ref. [189].

Figure 5

Examples of different scaffold pore configurations/raster patterns achievable through 3D printing. Reprinted with permission from ref. [192]. Copyright 2021 Elsevier Ltd.

Figure 8

Example of the interest of using shape memory scaffolds for minimally invasive implantation into large bone defects. Reprinted with permission from ref. [192]. Copyright 2021 Elsevier Ltd.