Intelligent electrospinning nanofibrous membranes for monitoring and promotion of the wound healing

Abstract

The incidence of chronic wound healing is promoted by the growing trend of elderly population, obesity, and type II diabetes. Although numerous wound dressings have been studied over the years, it is still challenging for many wound dressings to perfectly adapt to the healing process due to the dynamic and complicated wound microenvironment. Aiming at an optimal reproduction of the physiological environment, multifunctional electrospinning nanofibrous membranes (ENMs) have emerged as a promising platform for the wound treatment owing to their resemblance to extracellular matrix (ECM), adjustable preparation processes, porousness, and good conformability to the wound site. Moreover, profiting from the booming development of human-machine interaction and artificial intelligence, a next generation of intelligent electrospinning nanofibrous membranes (iENMs) based wound dressing substrates that could realize the real-time monitoring of wound proceeding and individual-based wound therapy has evoked a surge of interest. In this regard, general wound-related biomarkers and process are overviewed firstly and representative iENMs stimuli-responsive materials are briefly summarized. Subsequently, the emergent applications of iENMs for the wound healing are highlighted. Finally, the opportunities and challenges for the development of next-generation iENMs as well as translating iENMs into clinical practice are evaluated.

Keywords: Dressings; Electrospinning nanofibrous membranes; Intelligent; Real-time monitoring; Sensors; Wound healing.

Graphical abstract

Fig. 1

Number of annual publications. (A) The literary search is based on the terms ‘electrospinning dressing’ or ‘electrospun dressing’ in the ‘Web of Science’ database from 2000 to 2024; (B) The literary search is based on the terms ‘intelligent/smart electrospinning dressing’ or ‘intelligent/smart electrospun dressing’ in the ‘Web of Science’ database from 2000 to 2024.

Fig. 2

Schematic illustration of the intelligent electrospinning wound dressings integrated with various biomarkers detected sensors and advanced drug delivery systems for the real-time monitoring and early diagnosis, on-demand treatment, and the all-in-one management of wound healing.

Fig. 3

Overview of the classical wound healing phases vs regenerative medicine therapy approach. (A) Major wound healing events in a controlled spatial and precisely temporal response to injury. (B) Tissue repair (scarring) and tissue regeneration after injury. Adapted with permission from Ref. [52]. Copyright 2008, Nature Publishing Group.

Fig. 4

ENMs for promoting wound healing. (A) Schematic illustration of the preparation and application of chitosan-based bioactive coaxial nanofibers. Reproduced with permission of [100]. Copyright 2023, Elsevier; (B) Schematic illustration of multilayered nanofibrous scaffold of Polyvinyl alcohol/gelatin/poly (lactic-co-glycolic acid). Reproduced with permission of [101]. Copyright 2023, Elsevier; (C) Schematic illustration of curcumin-loaded sandwich-like nanofibrous membrane. Reproduced with permission of [102]. Copyright 2021, Elsevier; (D) Schematic illustration of the preparation of Preparation of PAHy/AgNPs nanofiber hydrogel mats. Reproduced with permission of [103]. Copyright 2024, Elsevier; (E) Antibacterial, anti-inflammatory, rapid hemostasis, and accelerated repair by multifunctional metal–organic frameworks fibrous scaffolds for diabetic wounds. Reproduced with permission of [104]. Copyright 2023, Elsevier; (F) Schematic diagram of bioactive electrospun nanoyarn-constructed textile dressing patches. Reproduced with permission of [105]. Copyright 2024, Elsevier; (G) Schematic diagram of the production and application of antibacterial and angiogenic wound dressings based on PHA fibrous scaffolds. Reproduced with permission of [106]. Copyright 2023, ACS; (H) Schematic illustration of DMOG@ZIF-8/Gelatin-PCL Electrospinning Dressing. Reproduced with permission of [107]. Copyright 2023, ACS; (I) Schematic illustration of novel bi-layered dressing patches constructed with radially-oriented nanofibrous pattern. Reproduced with permission of [108]. Copyright 2022, Elsevier.

Fig. 5

Temperature-Responsive iENMs. (A) Flexible Breathable Nanomesh Electronic Devices for On-Demand Therapy. Reproduced with permission of [121]. Copyright 2022, Wiley; (B) The fabrication of flexible and breathable on-skin electronic devices featuring temperature-sensing capability and temperature-sensitive on-demand drug release. Reproduced with permission of [109]. Copyright 2019, Wiley; (C) A schematic of the design, structure, and operational overview of a multifunctional IWD for managing wound exudate and treating chronic wounds. Reproduced with permission of [51]. Copyright 2023, Wiley.

Fig. 6

pH-Responsive iENMs. (A) Preparation technology of composite film; Antibacterial schematic diagram; Structure and unidirectional liquid delivery. Reproduced with permission of [143]. Copyright 2023, Elsevier; (B) Schematic illustration of the Janus wound dressing based on cellulose nonwovens for diabetic wound healing and monitoring. Reproduced with permission of [145]. Copyright 2023, Wiley. (C) Schematic diagram of GOx/CDs@MOF NF dressing for visual monitoring and antibacterial treatment of diabetic-infected wounds. Reproduced with permission of [144]. Copyright 2023, ACS.

Fig. 7

iENMs for Monitoring of other Wound Related Markers in Wound Healing. (A) Synthetic Scheme for the Nanofibrous and chromogenic response of membranes to P. aeruginosa (ATCC 27853) and MRSA (ATCC 33592) after 2 h incubation with bacterial lawns at various concentrations. Reproduced with permission of [158]. Copyright 2020, ACS; (B) Preparation process of bifunctional humidity-pressure sensor. Reproduced with permission of [30]. Copyright 2022, Wiley; (C) Schematic illustration of the fabrication of Janus conductive nanofibrous membrane, formation of bioinspired aligned wrinkles, and dual functions of the bioinspired dressing. Reproduced with permission of [159]. Copyright 2022, Wiley.

Fig. 8

Extended iENMs for non-wound marker monitoring. (A) Preparation diagram of Ti₃C₂T_x MXene/poly (ε-caprolactone)/gelatin coaxial electrospinning nanofibers membranes. Reproduced with permission of [27]. Copyright 2023, Springer; (B) Schematic illustration of the BC scaffold loaded with A-GNCs as antibacterial wound dressing to address the issue of MDR-infected skin wounds. Reproduced with permission of [162]. Copyright 2021, ACS; (C) Schematic illustration of the preparation process of intelligent scaffolds. Reproduced with permission of [163]. Copyright 2023, ACS; (D) The schematic diagram of the three-dimensional hierarchically interlocked PVDF/ZnO fibers-based PME for muscle behavior monitoring. Reproduced with permission of [164]. Copyright 2020, Elsevier.

Fig. 9

Shape memory and conductive iENMs. (A) The folding shape memory behavior of PCL-PEG-AT films. Reproduced with permission of [168]. Copyright 2019, Elsevier; (B) Schematic illustration of cell cultures on the 2D-ACNFs with electrical stimulation environment. Reproduced with permission of [169]. Copyright 2021, ACS; (C) (A1–3–C1–3) Fluorescence and (A4–C4) SEM images of hMSCs cultured on 2D aligned nanofibers before and after coating conductive polymer after 7 days cultured with/without electrical stimulation. Reproduced with permission of [169]. Copyright 2021, ACS.

Fig. 10

Applications of 3D-printed ENMs in Wound Healing. (A) Cell morphology of representative neonatal human dermal fibroblasts (NHDFs) for each mesh. Reproduced with permission of [183]. Copyright 2019, Springer; (B) SEM images of RAW 264.7 cells on 2D plate after day 1 (a) and day 5 culture (b); and on 3D PCL scaffolds after day 1 (c) and day 5 culture (d). Reproduced with permission of [184]. Copyright 2021, ACS; (C) The images of the blood-clotting. Reproduced with permission of [185]. Copyright 2022, Elsevier.

Fig. 11

Cocluster analysis of keywords in literatures on iENMs from 2010 to 2024.