Application of Biomedical Microspheres in Wound Healing

Abstract

Tissue injury, one of the most common traumatic injuries in daily life, easily leads to secondary wound infections. To promote wound healing and reduce scarring, various kinds of wound dressings, such as gauze, bandages, sponges, patches, and microspheres, have been developed for wound healing. Among them, microsphere-based tissue dressings have attracted increasing attention due to the advantage of easy to fabricate, excellent physicochemical performance and superior drug release ability. In this review, we first introduced the common methods for microspheres preparation, such as emulsification-solvent method, electrospray method, microfluidic technology as well as phase separation methods. Next, we summarized the common biomaterials for the fabrication of the microspheres including natural polymers and synthetic polymers. Then, we presented the application of the various microspheres from different processing methods in wound healing and other applications. Finally, we analyzed the limitations and discussed the future development direction of microspheres in the future.

Keywords: biomaterials; drug release; microspheres; tissue engineering; wound healing.

Figure 2

The different stages of wound healing [31]. Copyright 2020, The Royal Society of Chemistry. The stages of wound healing include hemostasis, inflammation, proliferation, and remodeling. After the skin injury, hemostasis begins. Platelets play a role in preventing blood loss. Then, neutrophils and monocytes play a role in preventing infection during the inflammation. The proliferation phase includes the formation of blood vessels and granulation tissue. Finally, myofibroblast further remodels the matrix during remodeling phase.

Figure 3

The different emulsion and phase separation methods. (a) Schematic of the fabrication of microspheres using single emulsion [47]. Copyright 2019, Elsevier B.V. All rights reserved. (b) Schematic of the fabrication of microspheres using double emulsion (W1/O/W2) [48]. Copyright 2022, Elsevier B.V. All rights reserved. (c) Schematic of the fabrication of the microspheres using the phase separation method and (i) SEM image of prepared microsphere. [35]. Copyright 2018, Elsevier Ltd.

Figure 6

The application of the drug delivery and hemostatic of the microspheres. (a) Schematic of the drug release from the CNPs@GMs on the wound bed. (b) Enzyme-responsive drug release from CNPs@GMs. (i) MMP9 expression in the wound of mice. (ii) The fluorescence change in Cur as the concentration of MMP9. (iii) Cur released curve from microspheres with MMP9 addition. (iv) Time course of Cur release [150]. Copyright 2018 American Chemical Society. (c) Schematic of PHM₄ absorbing the liquid from oozing blood. (d) Images of liver hemorrhage model (i) and femoral artery hemorrhage model (ii) after treatment with different method. [163]. Copyright 2019, American Chemical Society.

Figure 1

The diagram of microspheres in regard to the preparation, materials, and application.

Figure 4

The fabrication of the microspheres using electrospray technology. (a) Schematic illustration of the fabrication of the microspheres using MES. (b,c) The optical (b) and SEM (c) images of the microspheres (Alg/RS, Alg/RS/CS, IPA@ Alg/RS, IPA@Alg/RS/CS) [54]. Copyright 2022, The Authors. Advanced Science published by Wiley-VCH GmbH. (d) Schematic illustration of the fabrication of the core-shell microspheres using CES. (e) The real-time picture of electrospray process. (f–g) The optical (f) and SEM (g) images of the core-shell microspheres [55]. Copyright 2020, (The Author/The Authors).

Figure 5

The fabrication of the microspheres using the microfluidic technology. (a) Schematic of the fabrication of the GelMA microspheres using microfluidic technology of the device of flow-focusing channel. (b) Optical (i,ii) and SEM (iii,iv) images of GelMA microspheres [60]. Copyright 2022, Wiley-VCH GmbH. (c) Schematic of the fabrication of the PDDMs microspheres using microfluidic technology of the device of co-flow channel. (d) Optical image (i), diameter distribution (ii) and SEM (iii) images of the PDDMs microspheres [61]. Copyright 2021, Wiley-VCH GmbH. (e) Schematic of the fabrication of the PDMS microspheres using microfluidic technology of the device of T-junction channels. (f) SEM images of outer surfaces (i) and inter surfaces (ii) of the PDMS microspheres [62]. Copyright 2022, American Chemical Society.

Figure 7

The application of the anti-infection of the microspheres. (a) Schematic of the preparation and application of the CSO@PM microspheres. (b) The photographs and counts of P.aeruginosa colonies from the wound sites [170]. ** indicates p < 0.001 compared with control group. Copyright 2021, the author(s).

Figure 8

The application of the angiogenesis of the microspheres. (a) Schematic of the preparation and application of the MCS-Zn²⁺-VEGF microspheres. (i) Production of the recombinant VEGF and microsphere. (ii) The microspheres were used in the wound healing. (iii) The angiogenesis ability of the microspheres in the process of wound healing. (b) Angiogenesis ability of the MCS-Zn²⁺-VEGF microspheres used to treat the wound [177]. Copyright 2022, the Authors. Published by Elsevier Ltd.

Figure 9

The application of the tissue regeneration of the microspheres. (a) Schematic of the preparation of the mCSB@TA microspheres. (b) Schematic of the application of the mCSB@TA microspheres for wound healing. (i) The schematic of synergistic hemostasis of the microspheres. (ii) The schematic of wound healing process. (c) The healing process of the wound treated with different microspheres [160]. Copyright 2022, published by Elsevier Ltd.

Figure 10

The application of the microspheres. (a) Schematic of the fabrication and application of the microspheres encapsulated the NK cells. (b) The picture of the tumor and mice treated with different method. (c) The images of NK-92MI cells cultured in the microspheres at different times [185]. Copyright 2019, American Chemical Society. (d) Schematic of the fabrication and application of the bio-inspired dual-adhesive microspheres. (e) The micro-CT reconstruction images after treated with the microspheres [186]. Copyright 2023, springer Nature Switzerland AG.