Harnessing stimuli-responsive biomaterials for advanced biomedical applications

Abstract

Cell behavior is intricately intertwined with the in vivo microenvironment and endogenous pathways. The ability to guide cellular behavior toward specific goals can be achieved by external stimuli, notably electricity, light, ultrasound, and magnetism, simultaneously harnessed through biomaterial-mediated responses. These external triggers become focal points within the body due to interactions with biomaterials, facilitating a range of cellular pathways: electrical signal transmission, biochemical cues, drug release, cell loading, and modulation of mechanical stress. Stimulus-responsive biomaterials hold immense potential in biomedical research, establishing themselves as a pivotal focal point in interdisciplinary pursuits. This comprehensive review systematically elucidates prevalent physical stimuli and their corresponding biomaterial response mechanisms. Moreover, it delves deeply into the application of biomaterials within the domain of biomedicine. A balanced assessment of distinct physical stimulation techniques is provided, along with a discussion of their merits and limitations. The review aims to shed light on the future trajectory of physical stimulus-responsive biomaterials in disease treatment and outline their application prospects and potential for future development. This review is poised to spark novel concepts for advancing intelligent, stimulus-responsive biomaterials.

Keywords: biomaterials; biomedical; physical stimulation; stimulus‐responsive.

FIGURE 1

The application of physical stimulation biomaterials based on ultrasound, light, electricity, and magnetism in the field of biomedicine is summarized, as electrical stimulation of nerve regeneration. Reproduced with permission.^{[ 12 ]} Copyright 2019, John Wiley & Sons. Electrical stimulation of skin regeneration. Reproduced with permission.^{[ 13 ]} Copyright 2022, Elsevier. Electrical stimulation of bone regeneration. Reproduced with permission.^{[ 14 ]} Copyright 2020, Elsevier. Photothermal/photodynamic. Reproduced with permission.^{[ 15 ]} Copyright 2021, American Chemical Society. Ultrasound stimulated tissue repair. Reproduced with permission.^{[ 16 ]} Copyright 2023, Elsevier. Ultrasonic controlled release. Reproduced with permission.^{[ 17 ]} Copyright 2023, Elsevier. Targeting/controlled release. Reproduced with permission.^{[ 18 ]} Copyright 2021, Elsevier. Magnetic stimulation tissue repair. Reproduced with permission.^{[ 19 ]} Copyright 2021, John Wiley & Sons.

FIGURE 2

(A) Wireless electrical stimulation system. (i) Schematic diagram of wireless electrical stimulation; (ii) Electrode layer hidden under circuit layer; (iii) Working principle of the system. Reproduced with permission.^{[ 29 ]} Copyright 2021, John Wiley & Sons. (B) Principle of ultrasonic generation based on inverse piezoelectric effect: (i) Schematic diagram of the inverse piezoelectric effect and (ii) finite element simulation of the sound field of piezoelectric US transducer. Reproduced with permission.^{[ 37 ]} Copyright 2023, Elsevier. (C) Schematic diagram of tissue penetration by light stimulation, ultrasonic stimulation, and magnetic stimulation. Reproduced with permission.^{[ 11 ]} Copyright 2021, Elsevier.

FIGURE 3

Hypothesis of cell response to electrical stimulation. (A) Structural water damage. (B) Volume flow of electro seepage. (C) Asymmetric ion flow and voltage‐gated channel opening. (D) Mechanical sensation. (E) Redistribution of membrane composition and lipid rafts. Reproduced with permission.^{[ 1 ]} Copyright 2020, Elsevier.

FIGURE 4

Application of electrical stimulation‐response biomaterials for nerve repair. (A) Cell‐level mechanism of electrical stimulation promoting nerve repair. Reproduced with permission.^{[ 81 ]} Copyright 2023, Elsevier. (B) 3D culture of electrical stimulation‐response to nerve regeneration. Reproduced with permission.^{[ 84 ]} Copyright 2019, John Wiley & Sons. (C) Neural injury model and repair. Reproduced with permission.^{[ 89 ]} Copyright 2020, American Chemical Society. (D) Biobattery electrical stimulation system. Reproduced with permission.^{[ 42 ]} Copyright 2019, John Wiley & Sons.

FIGURE 5

Application of electrical stimulation in response to biomaterials in skin repair. (A) Electrical stimulation promotes improvement in skin repair cell levels. Reproduced with permission.^{[ 92 ]} Copyright 2021, John Wiley & Sons. (B) Visual monitoring of skin repair by electrical stimulation. (i) Electronic bandage system; (ii) enlarged view of the entire system; (iii) operational flow chart of the electronic system; (iv) electronic bandage system application sequence. Reproduced with permission.^{[ 13 ]} Copyright 2022, Elsevier.

FIGURE 6

Application of electrical stimulation‐response biomaterial for bone repair. (A) The electrical stimulation response regulates related proteins and enzymes to accelerate bone repair. (i) Schematic diagram of an electret‐based host‐coupling bio‐nanogenerator implanted onto the bone injury in vivo. (ii) Mechanism of bone repair. Reproduced with permission.^{[ 113 ]} Copyright 2021, Elsevier. (B) Preparation of electrical stimulation response system (i). Accelerates stem cell differentiation, regulates immunophenotype, reduces inflammatory expression, and reduces reactive oxygen species accumulation (ii). Accelerates bone repair (iii). Reproduced with permission.^{[ 114 ]} Copyright 2023, American Chemical Society.

FIGURE 7

Application of electrical stimulation‐response biomaterial for bone repair. Controlled release of growth factors to accelerate bone tissue regeneration. Reproduced with permission.^{[ 14 ]} Copyright 2020, Elsevier.

FIGURE 8

Photostimulation‐responsive biomaterial drug controlled release. (A) Low melting point gel intelligent photo controlled release system. Reproduced with permission.^{[ 145 ]} Copyright 2022, John Wiley & Sons. (B) Photocatalytic release system for reactive oxygen species regeneration. Reproduced with permission.^{[ 149 ]} Copyright 2021, John Wiley & Sons. (C) Photocatalytic release systems in anoxic environments. Reproduced with permission.^{[ 150 ]} Copyright 2021, Elsevier.

FIGURE 9

Ultrasonic stimulation‐response biomaterial for controlled release drugs. (A) liposomes loaded with indocyanine green and doxorubicin: (i) activation of cGAS‐STING signaling; (ii) induction of T cell immunity. Reproduced with permission.^{[ 177 ]} Copyright 2023, Spring Nature. (B) Dual‐response controlled release system regulates macrophage activation and T cell immunity. Reproduced with permission.^{[ 190 ]} Copyright 2022, American Chemical Society. (C) Controlled release system of CT imaging based on double stimulus response. Reproduced with permission.^{[ 195 ]} Copyright 2021, Royal Society of Chemistry. (D) Blasting release system for ultrasound/magnetic resonance dual‐mode imaging. Reproduced with permission.^{[ 196 ]} Copyright 2021, Elsevier.

FIGURE 10

Application of magnetic stimulation‐response biomaterials in tissue repair. (A) Collaborative regeneration of chemical and electrical signals based on magnetic response. Reproduced with permission.^{[ 209 ]} Copyright 2023, Elsevier. (B) Magnetic response electrical signals promote endogenous response and promote bone regeneration. Reproduced with permission.^{[ 216 ]} Copyright 2020, Elsevier. C. Magnetic response heat signal promotes endogenous response to kill cancer cells. Reproduced with permission.^{[ 218 ]} Copyright 2021, American Chemical Society. (D) Aggregation‐capture‐kill system based on magnetic response. Reproduced with permission.^{[ 223 ]} Copyright 2023, John Wiley & Sons.

FIGURE 11

Potential biosafety risks of nanoparticles: Acid degradation and recrystallization. Reproduced with permission.^{[ 204 ]} Copyright 2020, American Chemical Society.

FIGURE 12

Magnetic stimulation response biomaterial targeting and drug controlled release. (A) Recoverable magnetic response controlled release system. Reproduced with permission.^{[ 241 ]} Copyright 2021, John Wiley & Sons. (B) Fluorescence imaging based on magnetic stimulation response and triple synergistic tumor therapy. Reproduced with permission.^{[ 244 ]} Copyright 2020, Elsevier. (C) Magnetic stimulation in response to endogenous responses to tumor therapy. Reproduced with permission.^{[ 246 ]} Copyright 2022, American Association for the Advancement of Science.