Use of Nanoparticles in Tissue Engineering and Regenerative Medicine

Abstract

Advances in nanoparticle (NP) production and demand for control over nanoscale systems have had significant impact on tissue engineering and regenerative medicine (TERM). NPs with low toxicity, contrasting agent properties, tailorable characteristics, targeted/stimuli-response delivery potential, and precise control over behavior (via external stimuli such as magnetic fields) have made it possible their use for improving engineered tissues and overcoming obstacles in TERM. Functional tissue and organ replacements require a high degree of spatial and temporal control over the biological events and also their real-time monitoring. Presentation and local delivery of bioactive (growth factors, chemokines, inhibitors, cytokines, genes etc.) and contrast agents in a controlled manner are important implements to exert control over and monitor the engineered tissues. This need resulted in utilization of NP based systems in tissue engineering scaffolds for delivery of multiple growth factors, for providing contrast for imaging and also for controlling properties of the scaffolds. Depending on the application, materials, as polymers, metals, ceramics and their different composites can be utilized for production of NPs. In this review, we will cover the use of NP systems in TERM and also provide an outlook for future potential use of such systems.

Keywords: ceramic nanoparticles; metallic nanoparticles; nanoparticles in bioinks; polymeric nanoparticles; regenerative medicine; tissue engineering.

Figure 1

Examples of different types (ceramic, polymeric, metallic) nanoparticles which can be utilized for various applications in TERM including tissue targeting and imaging, bioactive agent delivery, modulating mechanical properties of scaffolds, providing antimicrobial and antitumor properties.

Figure 2

Real-time images of cancer cell division under the following conditions: (A) with No AuNPs and (B) in the presence of 0.4 nM nuclear-targeting gold nanoparticles (RGD/NLS-AuNPs). Red stars indicate the nuclei. Scale bar: 10 μm. Reprinted from Kang et al. (2010) with permission from American Chemical Society. (C) Preparation of targeted surface-enhanced Raman scattering (SERS) NPs by using a mixture of SH-PEG and a hetero-functional PEG (SH-PEG-COOH). Covalent conjugation of an EGFR-antibody fragment occurs at the exposed terminal of the hetero-functional PEG. Reprinted from Qian et al. (2008) with permission from John Wiley and Sons. (D) Scheme representing the use of AuNPs in tissue engineering and regenerative medicine. Reprinted from Vial et al. (2017) with permission from Elsevier.

Figure 3

Effect of silver nanoparticles on burn wound healing. (A) Synthesis mechanism of silver nanoparticles using bamboo leaves extract (BLE) to reduce silver nitrate. Reprinted with permission from Yasin et al. (2013) (B) Images of burn wound from mouse treated with silver nanoparticles (ND) and silver sulfadiazine (SSD) at different time point of wound healing. Reprinted from Tian et al. (2007) with permission from Springer.

Figure 4

Development of a hybrid CaCO₃ particular system doped with ECM components (gelatin, hyaluronic acid, fibronectin) for creating a building block strategy. Confocal images of the after 3 days of culture. The particles are labeled in green (stained by HA-FITC) and the fibroblasts were visualized with Rho-Phalloidin (red) and nuclei (blue). Reprinted with permission from Affolter-Zbaraszczuk et al. (2017).

Figure 5

A merged fluorescence confocal image of FMN–MTNs (green dots) in BT-20 cancer cells where the nuclei were stained with DAPI (blue spots). Reprinted from Wu et al. (2011) with permission from The Royal Society of Chemistry.

Figure 6

Different polymeric nanoparticles (PNPs) based on composition, manufacturing process, and structure.

Figure 7

(A) Schematic illustration of fabrication process of nerve conduit with aligned fibers for axon outgrowth direction guidance and neurotrophic concentration gradient to attract the regenerated axon. (B–E) Nerve regeneration in the rabbit sciatic nerve transection model. (B) Sciatic nerve before surgery. (C–E) After surgical implantation of multichanneled scaffold combined with aligned nanofibers and neurotrophic gradient (MC/AN/NG) nerve conduit for 8, 16, and 24 weeks, the repaired nerve was clearly observed. The arrowhead indicates the regenerated sciatic nerve. (P, proximal end; D, distal end). Reproduced from Chang et al. (2017) with permission from American Chemical Society.

Figure 8

(A) Fabrication of AIE-Tat NPs based on PITBT-TPE Fluorogen (B–D) Fluorescent images of mouse bone marrow MSCs grown on an HA scaffold. (E–G) RT-PCR results of OPN, BMP2, Col I, and ALP gene expression in AIE-Tat NP-labeled and unlabeled mouse bone marrow MSCs after osteogenic induction for 3, 7, and 14 days. Reproduced from Gao et al. (2016) with permission from American Chemical Society.

Figure 9

(A-C) Osteogenic differentiation of 3T3 cells under inflammatory state. (A) ALP staining and (B) ALP quantitative assay of 3T3 cells after cultured for 7 and 14 days. (C) mRNA expression of osteogenesis-related genes (ALP, OCN, OPN, COL1, RUNX2) in 3T3 cells cultured for 7 and 14 days. ^*p < 0.05 vs. BGSE (bioactive glass scaffolds extracts) group; ^#p < 0.05 vs. RAW (macrophage-like cell line) group. (D–F) Osteogenic differentiation of 3T3 cells in anti-inflammatory state. (D) ALP staining and (E) ALP quantitative assay of 3T3 cells after being treated with various samples for 7 and 14 days. (F) mRNA expression of osteogenesis-related genes (ALP, OCN, OPN, COL1, RUNX2) of 3T3 cells incubated with various groups for 7 and 14 days. ^*p < 0.05 vs. blank control; ^#p < 0.05 vs. BGSE group. Reproduced from Zhao et al. (2018) with permission from John Wiley and Sons.