The literature search was conducted in electronic databases for the years 2019–2023. The search strategy in PubMed was as follows: ((“Diabetic Foot”[Mesh]) OR (Diabetic foot ulcer[Title/Abstract])) AND ((“Printing, Three-Dimensional”[Mesh]) OR ((((((((((((((((((((3D printing[Title/Abstract]) OR (Printing, Three Dimensional[Title/Abstract])) OR (Printings, Three Dimensional[Title/Abstract])) OR (Three-Dimensional Printings[Title/Abstract])) OR (3-Dimensional Printing[Title/Abstract])) OR (3 Dimensional Printing[Title/Abstract])) OR (3-Dimensional Printings[Title/Abstract])) OR (3-Dimensional Printings[Title/Abstract])) OR (Printings, 3-Dimensional[Title/Abstract])) OR (3-D Printing[Title/Abstract])) OR (3 D Printing[Title/Abstract])) OR (3-D Printings[Title/Abstract])) OR (Printing, 3-D[Title/Abstract])) OR (Printings, 3-D[Title/Abstract])) OR (Three-Dimensional Printing[Title/Abstract])) OR (Three Dimensional Printing[Title/Abstract])) OR (3D Printing[Title/Abstract])) OR (3D Printings[Title/Abstract])) OR (Printing, 3D[Title/Abstract])) OR (Printings, 3D[Title/Abstract]))). In addition, the reference lists of the included articles were investigated to identify other relevant articles that could not be found through the initial electronic search strategy.

Studies related to the use of 3D printing technology in DF were included. Studies, review papers, book chapters, conference abstracts, reviews and research protocols published in any language other than English were excluded. The first step was to eliminate duplicate articles by looking at titles and abstracts through EndNote. Next, titles were screened to remove irrelevant articles. Then, abstracts and full texts of relevant articles were read and screened for inclusion based on predefined criteria. Finally, criteria-compliant articles were included.

A total of 25 identified articles based on database search and citation network analysis. After removing duplicates, 18 articles remained, and three articles that did not meet the inclusion criteria were removed after reading the title/abstract. A total of 97 relevant articles were included during the reading of references. In total, 112 articles were included. The flow chart of this study was presented in Figure 1.

The paucity of drugs for DFU treatment in the clinic is partly due to the lack of good experimental models to predict their effects. The mouse model is superior to the human body in terms of wound repair due to the abundance of hair follicle stem cells and growth factors, leading to the questioning of the mouse-based diabetes model (Phang et al., 2021). The 3D printed of DFUs model resembles human skin in anatomical structure, mechanical and biochemical features, and transcriptomics and proteomics also show similarities to human skin development (Admane et al., 2019). The analysis of the 3D models is presented in Table 1.

3D printing-based skin models can accelerate wound healing by reducing inflammation, inhibiting fibrosis or increasing angiogenesis or regeneration (Kondej et al., 2024).3D skin modelling is divided into scaffold and scaffold-free systems, with scaffold modelling being widely used due to altered porosity, surface chemistry and permeability. Scaffolds composed of biopolymers mimic the extracellular matrix (ECM) and provide support and signals to cells, creating organotypic models that mimic native human skin (Phang et al., 2022). Cross-linked polymer hydrogels and matrix gels are commonly used scaffold materials, in addition to nanofibers, collagen sponges, agarose peptide microgels, polystyrene and polycaprolactone (Mohandas et al., 2023). Stent materials function differently and are used to replicate disease outcomes. 3D printed scaffolds are convenient, support high cellular loads and remain viable to accelerate healing, and also deliver stable antibiotics for effective treatment of chronic wounds (Sun et al., 2018; Glover et al., 2023). Intini et al. fabricated chitosan (CH) porous 3D printed scaffolds for skin regeneration. They loaded normal human dermal fibroblasts and keratin-forming cells into the scaffold holes to form a skin-like layer. The CH scaffolds promoted wound healing in diabetic rats compared to commercial patches and self-healing (Intini et al., 2018). Furthermore, the scaffold-free system serves as a scaffold alternative structure that alleviates poor biocompatibility. Such systems are essential for analyzing ECM protein regulation in human skin and can transfer cells from two to three dimensions, inducing deep upregulation of matrix body proteins and generating complex tissue-like ECM (Vu et al., 2021). Engineered skin substitutes cannot fully mimic the complex native environment of wound healing. However, 3D printed scaffolds offer a solution to the recurrent problem of limited donor tissues and high donor site morbidity seen in tissue transplantation, while in vitro their fragile structure may lead to tissue damage, and in vitro bioprinting and artificial implantation carry the risk of contamination (Tan et al., 2022; Singh et al., 2020).

Fibroblast growth factor (FGF) is an important factor to consider in the design of DFU models. 3D human skin equivalent (HSE) models consisting of cells from DFU patients can induce an inflammatory response and have been used to study diabetic inflammation, drug testing, and to reduce reliance on animal-derived ECM (Smith et al., 2021; Smith et al., 2020). The researchers also developed a three-dimensional hyperglycemic wound model of normal human keratinocytes, demonstrating common phenotypes of DFU such as re-epitheliazation, granulation and damage caused by keratinocyte over-proliferation (Phang et al., 2021). Induced pluripotent stem cells (iPSCs) were generated from fibroblasts of patients with diabetes and from fibroblasts of healthy persons harvested from skim. They were modified and induced to differentiated into fibroblasts. Research has found that the gene expression and characteristic matrix composition exhibited by iPSC-derived fibroblasts in 3D dermal-like tissues were similar to those of primary fibroblasts, and they continuously promoted matrix remodeling and wound healing in chronic wound environments, demonstrating therapeutic potential. IPSC reprogramming is considered effective in promoting cell healing to eliminate genetic traits (Pastar et al., 2021; Kashpur et al., 2019). Currently, there are still challenges in printing biological models in high permeability and high glucose environments. Based on existing studies progress, we need to develop more mature DF trauma models.

DF vascular injury and impaired healing of diabetic ulcers are associated with poor angiogenesis of granulation tissue (Lin et al., 2019). Hyperglycemia induced increased production of reactive oxygen species and the exacerbation of apoptosis during ischemia (Han et al., 2021) which it is also considered an influential factor in the injury of DFUs. The 3D endothelial cell germination test is more reflective of the angiogenic process of endothelial cells than the traditional 2D test and can be used as a screening tool for hyperglycemic applications (Phang et al., 2021). 3D printed endothelial progenitor cell skin patches together with adipose-derived stem cells accelerate wound closure, re-epithelialization, neovascularization and blood flow (Kim et al., 2018). 3D printing not only significantly improves the flexibility and precision of in vitro modelling, but also dramatically reduces costs and shortens development cycles through high customisation, rapid fabrication of complex structures, and the use of a wide range of biocompatible materials. This technology facilitates interdisciplinary integration and strengthens collaboration between biology, medicine and engineering, making it a key tool to support innovation in multiple fields such as clinical research, drug screening and disease modelling. The application of joint 3D printing technology to manufacture experimental models is presented in Figure 2.

Adipose tissue contains high levels of cell growth factors that can promote angiogenesis and wound remodeling (Lavery et al., 2007). Furthermore, anti-inflammatory cytokines and healing-related peptides may positively affect wound healing (Pallua et al., 2009). Thus, autologous micro-fragmented adipose tissue can significantly improve the healing of small amputations following DFU surgery (Lonardi et al., 2019). For patients, subcutaneous liposuction to extract fat cells is relatively simple and less painful (Gimble et al., 2007). In a single-arm pilot study, ten patients with chronic DFUs were treated with autologous minimally manipulated homologous adipose tissue (AMHAT). During follow-up, the patient wounds healed well (Armstrong et al., 2022). 3D printing was combined with minimally manipulated ECM (MA-ECM) to create bio scaffolds that increase the speed of wound healing in patients (Kesavan et al., 2021; Kesavan et al., 2024; Yoon and Song, 2024). Fibrin gel is biocompatible and mimics the clotting process, reduces inflammation, and promotes cell adhesion and proliferation to accelerate healing. In addition, it has good mechanical strength. Thus, Fibrin gel was added to a 3D-AMHAT scaffolds, which not only promote wound healing, were easily absorbed without interfering with the healing process, but were also strong enough to withstand changes in mechanical stress during the healing process, thus further accelerating wound healing (Bajuri et al., 2023). By combining autologous adipose tissue and 3D printing technology to create a biocompatible and mechanically robust scaffold, the effectiveness and speed of diabetic foot wound healing can be significantly improved. 3D printing combined with autologous fat grafting helps DF wounds healing and is considered a new approach to treatment at DFUs.

Transverse tibial bone transfer (TTBT) is a novel surgical approach to treat DFUs, and several clinical trials have confirmed its efficacy (Godoy-Santos et al., 2017; Kallio et al., 2015). However, during conventional bone transfer, the periosteum may be damaged, and deviations in the angle of screw placement can result in the direction of bone transfer that is not perpendicular to the slice, which can lead to postoperative spatial heterogeneity on both sides of the body and affect the growth of the microvascular network (Randon et al., 2010). Yuan-Wei Zhang et al. performed TTBT under the guidance of a 3D-printed guide plate with DM patients. This new technique is effective in preserving the relative integrity of the bone window and periosteum. Moreover, surgeons can simulate the surgical plan on a 3D model, improving the accuracy of the operation (Wang et al., 2023).

DFU is characterized by persistent chronic inflammation, granulation tissue formation, and reduced vascularization (Hu and Xu, 2020). Single dressings have limited effect, DFU dressings are enhanced with bioactive molecules. Hydrogels are considered to be excellent wound dressings (Tran et al., 2023; Feng et al., 2023; Sarkar and Poundarik, 2022; Glover et al., 2021; Gomes et al., 2020). Multifunctional bioprinter dressing increase the thickness of wound granulation tissue and promote the formation of blood vessels, hair follicles and collagen fiber networks (Huang et al., 2022). For examples: The addition of VEGF to 3D-printed dressings enhanced the proliferation of endothelial cells, promoted the formation of blood vessels in the body, and accelerated wound healing. Interleukin four and antioxidant-rich autologous bio gel protected fibroblasts in patients with diabetic foot ulcers (DFUs) and facilitated wound healing (Tan et al., 2020; Mashkova et al., 2019; Yang et al., 2022). In another development, a silver vinyl-based 3D-printed antimicrobial ultra-porous polyacrylamide (PAM)/hydroxypropyl methylcellulose (HPMC) hydrogel dressing was designed with a porosity of 91.4%. It featured open channels that allowed it to absorb water rapidly, taking in up to 14 times its own weight. The large pores helped reduce swelling, minimized the risk of dressing dislodgment, and promoted the healing of infected wounds (Liu et al., 2021). Furthermore, 3D-printed silver gelatin dressings demonstrated good antimicrobial properties and promoted wound healing. A hydrogel infused with nanofibers was used to synthesize tissue-like structures and was applied to rat skin breaks, showing excellent biocompatibility and antibacterial effects (Bahmad et al., 2021; Jin et al., 2023; Wan et al., 2019). Additionally, the encapsulation of antimicrobial peptides and PDGF-BB into porous 3D radially aligned nanofiber scaffolds (RAS) allowed for the recruitment of fibroblasts, endothelial cells, and keratinocytes to clear bacterial infections and enhance granulation tissue formation (Li et al., 2024). The researchers also undertook a technological update to develop a coaxial microfluidic 3D bioprinting technology combining flow-assisted dynamic physical crosslinking and calcium ion chemical dual crosslinking method, designing a biologically active multilayer core-shell fibrous hydrogel loaded with PRP. The prepared hydrogel exhibited excellent water absorption and retention capabilities, good biocompatibility, and broad-spectrum antibacterial effects (Huang et al., 2023). The combination of 3D printing technology and biomaterials such as cytokines enables wound dressings to be personalized, with precise control of the material structure, multifunctional, and effective in promoting angiogenesis, tissue regeneration and optimizing drug release. This significantly improves wound healing efficiency and therapeutic efficacy. The analysis of the 3D-printed therapies is presented in Table 2. And The application of 3D printing technology combined with biological materials in surgery and wound care was presented in Figure 3.

3D printing-assisted customized insoles can reduce the incidence of DFUs and reduce plantar pressure, thereby mitigating the risk of DFUs and infections (Leung et al., 2022). Below we present the application of 3D printing-assisted manufacturing of insoles in diabetic foot management.

By measuring the temperature difference between the same parts of the feet, we can find the potential risk of DFUs and the common alert threshold is 2.2°C (Lavery et al., 2004). Patients doing self-care at home are often unable to accurately self-assess their condition, and are often treated too late when their feet become necrotic. The researchers used foot sensors to measure differences in skin temperature, which alerts when the temperature reaches an alarm threshold, and the data can be displayed, stored, or transmitted. However, existing devices are unable to study the complex dynamics of temperature changes over time (Martín-Vaquero et al., 2019). Recent studies have used 3D printed insoles equipped with personalized anatomical sensors to continuously monitor foot temperature, taking into account individual differences. A study showed that foot temperatures rose significantly faster in diabetic patients than in controls in the sitting position, at the bunion and at the head of the fifth metatarsal. This was the first time that foot temperature changes between two groups was quantified and may reveal new biomarkers associated with differences in soft tissue and angiogenesis (Beach et al., 2021). Furthermore, sensor-based insoles should also consider humidity parameters when detecting pressure and temperature (Tian et al., 2024). In another study, the multifunctional Janus membrane (3D chitosan sponge-ZE/polycaprolactone nanofibers-ZP) is thought to monitor and treat diabetic wounds, with its unidirectional water transport and strong antimicrobial capacity aiding wound healing. The membrane also monitors wound status through color and fluorescence changes, providing a basis for early intervention in diabetic patients (Liu et al., 2024).

According to international guidelines, effective assessment of the size and depth of diabetic foot ulcers improves treatment success. Current assessment methods include the use of disposable rulers and metal probes (Monteiro-Soares et al., 2020). However, there are several drawbacks, including subjective error, variability in measurement time, horizontally transmitted infections and clinical waste (Fernández-Torres et al., 2020). In response to changes in ulcer size, the researchers developed the WAM 3D monitoring camera for wound assessment, which is not limited by wound size, is particularly effective in measuring heels, toes, and curved areas of the body, and is a non-invasive means of reducing the risk of infection, with digitized images suitable for telemedicine applications (Jørgensen et al., 2018; Rasmussen et al., 2015). A study analyzed 63 ulcers in 38 diabetic foot patients and found that a 3D camera effectively measured the ulcerated area and that the measurements correlated linearly with healing time, which could be used as a prognostic marker and an early identification criterion, as well as an indicator of medication efficacy (Lasschuit et al., 2021; Malone et al., 2020; Vangaveti et al., 2022). However, we still need new experiments to establish this modality.

Thermal imaging technology provides early warning and prevention of DFU by monitoring temperature changes in the feet of diabetic patients. However, commonly used infrared cameras can only capture 2D images, requiring multiple shots to obtain a complete ulcer view. Such operation is not feasible in an already busy clinical practice and at home (van Doremalen et al., 2020; Liu et al., 2015; Rismayanti et al., 2022). Therefore, the researchers used 3D infrared imaging to overcome the shortcomings of two-dimensional imaging. The technique clearly shows the temperature difference between ulcers and normal tissue, identifies potential ulcers and danger zones, and also detects diffuse temperature elevation, suggesting inflammation or infection. It is able to analyze information about ulcers and differentiate between background and normal tissue, and the camera’s viewing angle and distance have a low impact on imaging (Liu et al., 2015). 3D optical cryo-imaging was used to assess the redox state of DFU wounds. In experiments, wound redox status in diabetic mice was quantified by in vivo fluorescence and 3D optical cryo-imaging and found to be correlated with mitochondrial dysfunction and increased oxidative stress, as well as the wound size. This technique can be used as a non-invasive indicator to assess complex wound healing (Mehrvar et al., 2019). Specific benefits of 3D printing technology in the manufacture of assistive devices include: individualized customization for patients, providing unparalleled comfort and functionality; orthopedic appliances designed to better fit the patient’s bone and muscle structure, reducing pressure points and enhancing orthopedic performance; rehabilitation devices such as gait trainers, which are customized to incorporate biomechanical modelling to improve the efficiency of rehabilitation; and sports aids such as knee pads and insoles, which reduce the risk of sports injuries and enhance sports performance through precise fit. In addition, 3D printing can also facilitate the upgrading and updating of diabetic foot testing equipment. These innovations not only enhance the functionality and user experience of assistive devices, but also promote the popularity and cost-effectiveness of personalized healthcare services. The application of 3D printing technology in assistive devices and ulcer monitoring is shown in Figure 4.