Bone biomaterials and interactions with stem cells

Abstract

Bone biomaterials play a vital role in bone repair by providing the necessary substrate for cell adhesion, proliferation, and differentiation and by modulating cell activity and function. In past decades, extensive efforts have been devoted to developing bone biomaterials with a focus on the following issues: (1) developing ideal biomaterials with a combination of suitable biological and mechanical properties; (2) constructing a cell microenvironment with pores ranging in size from nanoscale to submicro- and microscale; and (3) inducing the oriented differentiation of stem cells for artificial-to-biological transformation. Here we present a comprehensive review of the state of the art of bone biomaterials and their interactions with stem cells. Typical bone biomaterials that have been developed, including bioactive ceramics, biodegradable polymers, and biodegradable metals, are reviewed, with an emphasis on their characteristics and applications. The necessary porous structure of bone biomaterials for the cell microenvironment is discussed, along with the corresponding fabrication methods. Additionally, the promising seed stem cells for bone repair are summarized, and their interaction mechanisms with bone biomaterials are discussed in detail. Special attention has been paid to the signaling pathways involved in the focal adhesion and osteogenic differentiation of stem cells on bone biomaterials. Finally, achievements regarding bone biomaterials are summarized, and future research directions are proposed.

Figure 1

The chemical composition and multi-scale structure of natural bone.

Figure 2

(a) Load vs displacement plot and (b) elastic modulus for HA and BNNT/HA obtained by nanoindentation. (c) Sword-in-sheath phenomenon and (d) bridging mechanism of BNNTs.

Figure 3

(a) Degradation behavior of silk fibroin protein/chitosan in 0.05 M phosphate-buffered saline (PBS) solution containing 1.6 μg·mL⁻¹ lysozyme and in pure PBS solution (pH 7.4). (b) pH changes of the resultant solution. ***, **, and * indicate significant differences between groups at P<0.001, P<0.01 and P<0.05, respectively. The results showed that the biodegradation and stability of chitosan could be modified by silk fibroin protein.

Figure 4

Commonly used strategies for improving the corrosion resistance of Mg and its alloys: (a) purification, (b) alloying, (c) surface coating, and (d) rapid solidification.

Figure 5

(a) The process of preparing porous Mg and an in vivo animal model. Step 1: an entangled 3D structure was prepared with Ti wires. Step 2: a Ti-Mg composite was prepared by the infiltration of Mg melts. Step 3: Ti wires were removed by hydrofluoric acid solution, yielding porous Mg. Step 4: the porous Mg was implanted into the lateral epicondyle of rabbits. (b) Characterization of the porous Mg and newly formed bone by micro-CT in 2D (red arrows) and 3D (white in color) reconstructions, showing a faster degradation and more bone regeneration for 400-PMg than 250-PMg at both time points. Here, 250-PMg and 400-PMg refer to porous Mg with a pore diameter of 250 and 400 μm, respectively. (c) Osteogenic differentiation and quantitative analysis of bone volume fraction and trabecular number and thickness, indicating a more densely packed bone structure for 400-PMg than 250-PMg.

Figure 6

(a) Schematic illustration of MSC-modified chitosan bone model with different contents of microcrystalline HA (mHA), nanocrystalline HA (nHA), and amorphous HA fabricated by freeze-drying. SEM images showed a macroporous topography akin to that of cancellous bone with pore diameters of tens of micrometers. (b) Improved cell proliferation in the 10% nHA/chitosan bone model after 1, 3, and 5 days. *P<0.01 compared with the chitosan controls at day 1, and *P<0.01 compared with all other scaffolds at day 5. (c) Confocal microscopy images of cell distribution (red color) in the 10% nHA/chitosan bone model (green color) after 24 h. High-magnification image showing the deposited ECM components.

Figure 7

(a) Image of the SGN 3D biomaterials. SEM images of (b) the SGN used and (c) the porous structure of the SGN 3D biomaterials. (d) Gene expression analysis of an osteoblast gene marker (runt-related gene 2 (RUNX2)) and a fibrocartilage gene marker (SOX9) after 1, 3, and 6 days of cell culture under control conditions (ADSCs seeded in culture wells without a scaffold) or in the presence of the SGN 3D biomaterials. (e) Water-soluble tetrazolium salt proliferation assay of ADSCs under control conditions or in the presence of the SGN 3D biomaterials for 1, 3, and 6 days (*P<0.05, **P<0.01).

Figure 8

The interactions between bone biomaterials and MSCs.

Figure 9

The signaling pathway in the adhesion of stem cells to bone biomaterials.

Figure 10

The main signaling pathways in the osteogenic differentiation of MSCs induced by biomaterials.