A Review on Hydrogels with Photothermal Effect in Wound Healing and Bone Tissue Engineering

Abstract

Photothermal treatment (PTT) is a promising strategy to deal with multidrug-resistant bacteria infection and promote tissue regeneration. Previous studies demonstrated that hyperthermia can effectively inhibit the growth of bacteria, whereas mild heat can promote cell proliferation, further accelerating wound healing and bone regeneration. Especially, hydrogels with photothermal properties could achieve remotely controlled drug release. In this review, we introduce a photothermal agent hybrid in hydrogels for a photothermal effect. We also summarize the potential mechanisms of photothermal hydrogels regarding antibacterial action, angiogenesis, and osteogenesis. Furthermore, recent developments in photothermal hydrogels in wound healing and bone regeneration applications are introduced. Finally, future application of photothermal hydrogels is discussed. Hydrogels with photothermal effects provide a new direction for wound healing and bone regeneration, and this review will give a reference for the tissue engineering.

Keywords: angiogenesis; antibacterial; bone regeneration; hydrogel; photothermal effect; wound healing.

Figure 1

Hyperthermia effects on the antibacteria via changing cell membrane permeability, enzyme inactivation, and protein denaturation [95]. Copyright 2021, Elsevier.

Figure 2

SEM images of S. aureus (a–c) and E. coli (d–f) after culture on PVA/CuS/MoS₂ hydrogels with NIR/visual light irradiation for 15 min. (a,d) PVA hydrogel, (b,e) CuS incorporated PVA hydrogel, and (c,f) CuS/MoS₂-incorporated PVA hydrogel [104]. Copyright 2020, Elsevier.

Figure 3

The effect of heat stimulation and Fe/Si ions on gene (in vitro) and protein (in vivo) expression. (a) bFGF, (b) bFGFR, (c) VEGF, (d) HIF-1α, (e) eNOS, (f) HSP90 gene expression of HUVECs at day 7. (g) Immunohistochemical staining for HSP90 (Blank: no treatment; CS-NOCS: calcium silicate-NOCS composite hydrogels without NIR irradiation; FA-NOCS: FA-NOCS composite hydrogels without NIR irradiation; FA–NOCS–L: FA-NOCS composite hydrogels with NIR irradiation (808 nm, 0.36 W/cm², 15min/day, day 1–5); L: laser irradiation only; Bar = 50 μm). (h) Possible activation mechanism of the combined effect of ions and thermal stimulation on angiogenesis. (B: blank; F: Fe²⁺ containing medium; S: SiO₄⁴⁻ containing medium; FS: Fe²⁺ and SiO₄⁴⁻ containing medium; H–B: heat treatment; H-FS: combination of heat and Fe²⁺ and SiO₄⁴⁻ ion treatment, * p < 0.05, ** p < 0.01). [112] Copyright 2020, Elsevier.

Figure 4

Mechanism of in situ mineralization of BP/agarose hydrogels under NIR irradiation [124]. Copyright 2020, Wiley.

Figure 5

Activation of NIR-BMP-2-HG triggered by NIR light. (A) NIR-BMP-2-HG, polymerized with the indicated concentration of HGNP, were cultured for 1 day and then irradiated with NIR laser for the indicated times. (B) BMP-2 concentration in media conditioned by NIR-BMP-2-HG polymerized with 30 μg·mL⁻¹ HGNP. (C) NIR-BMP-2-HG, polymerized with 30 μg·mL⁻¹ HGNP, were NIR-irradiated in the presence of 10 nM Rm or 100 nM rapalog AP21967 (Rl). Timeline scheme of NIR-BMP-2-HG preparation, NIR irradiation of hydrogel (NIR), * p < 0.05, culture in the absence (-Rm/Rl) or presence (+Rm/Rl) of rapamycin or rapalog and analytical assays [127]. Copyright 2020, Elsevier.

Figure 6

In vivo animal experiment assessment of hydrogels for wound healing. (A) Images of wounds treated with different hydrogels on 0, 3, 7, and 14 d. (B) Wound area values at different healing times. (C) H&E staining and (D) Masson’s trichrome staining of the wound section at 3, 7, and 14 d; scale bar = 100 μm. (ZP: ZIF8/PDA, BZP: BNN6/ZIF8/PDA) [121]. Copyright 2020, Elsevier.

Figure 7

Micro-CT scanning and sequential fluorescent labeling. (A) Representative 3D reconstruction of the 4 mm calvarial defect from each group; (B) quantitative comparison of Tb.N, BV/TV and BMD among the control, constant release and pulsatile release groups. (C) Sequential fluorescent labeling of alizarin red (red) and calcein (green) represented the bone formation at 3 and 6 weeks. * p < 0.05 compared to the control group, # p < 0.05 compared to the constant release group. Scale bar = 20 μm [153]. Copyright 2021, Elsevier.