Application of Nanofiber Wound Dressings in Diabetic Wound Healing: A Review and Economic Considerations

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The use of nanofiber dressings for diabetic wound healing is an emerging area of research; these dressings offering a biodegradable framework that mimics extracellular matrix (ECM), thus potentially enhancing the rate of wound healing.^1,2 In addition to desirable wound dressing characteristics, nanofiber morphology, including pore size, fiber diameter, and polymer used, are easily tunable.^1,2 Importantly, nanofibers provide a simple way to integrate small molecule drugs to allow for slow, sustained, localized release, thus preventing the adverse effects associated with systemic and traditional topical administration.³ Similarly, the release profile of the drugs is simple to adjust depending on desired characteristics.^4,5 Nanofibers are a promising novel wound dressing with potential to accelerate wound healing, prevent or treat infection, and act as a scaffold for healing wounds. Application of these dressings to diabetic wounds may improve clinical outcomes and quality of life, making this an important area of research. 

This review examines the current landscape of research into nanofiber dressings and discusses the implications of these novel dressings compared with the current standard of care.

A scoping review was conducted utilizing PubMed and Embase for studies published up until January 2025, including studies investigating nanofiber wound dressings loaded with a therapeutic agent in diabetic models. The search terms included diabetic wound, diabetic ulcer, diabetic foot ulcer, chronic wound, delayed wound healing, electrospun nanofiber, nanofiber scaffold, and electrospun mat. The query was developed using key words in conjunction with the now retired ChatGPT-4o model (OpenAI) following the PubMed Advanced Search Builder syntax. Studies were excluded if nanofibers were not used as a wound dressing, if the nanofiber dressings did not integrate a therapeutic agent, or if the study did not evaluate the therapy in a diabetic model.

Nanofiber scaffolds have excellent biocompatibility, provide continuous localized drug delivery, create an optimal microenvironment for wound healing, improve exudate absorption, have high porosity that allows for gas exchange, and block the invasion of microbes due to nanopore size exclusion, making nanofibers a good candidate for a singular treatment modality in diabetic wound healing.² Local, controlled, and sustained drug delivery has the potential to improve wound healing. Systemic administration leads to potential off-target side effects, low bioavailability at the desired target, and poor selectivity. Compared with the currently available local drug delivery systems (hydrogels, films, sponges, and foams), nanofiber scaffolds are more convenient for the incorporation of therapeutic compounds, have hemostatic properties, have better conformation to wound surface due to flexibility, have less scar potential, and reduce the frequency of bandage changes.³ These beneficial properties can potentially improve patient compliance through enhanced comfort, the possibility of a superior cosmetic result, and decreased dedicated care time needed. 

The unique properties of nanofiber wound dressings are derived from unique surface features resulting from the nanometer-diameter size, including enhanced mechanical strength and high surface-to-volume ratio.⁶ Studies incorporating therapeutics into nanofiber dressings have been applied in diabetic wound healing models, including murine and cell lines, yielding further healing benefit compared with nanofiber dressings alone.^1,3,7 Uniquely, nanofiber dressings have tunable characteristics depending on the polymer type, the ratio or combination of polymers used, and the methods used to fabricate the nanofiber. This allows the nanofiber dressing to be adjusted to the desired drug release characteristics, making nanofiber dressings a great candidate for controlled drug release for a wide variety of therapeutics.⁸ Similarly, the rate of drug release and the mechanical properties can be modulated through chemical and physical crosslinking.^4,5 

Nanofiber dressings are fabricated by bioprinting, microfluidic spinning, wet spinning, dry spinning, and electrospinning.⁶ Electrospinning has frequently been used as a technique for development of nanofiber dressings for wound healing because of the high surface area–to-volume ratio, flexibility, simple preparation, wide material compatibility, ease of incorporation of therapeutic products, scalability, and easily tunable characteristics.^6,8 In the electrospinning process, a polymer solution acts as a positive electrode directed at a negatively charged collector in the presence of a high electrical field and a very low flow rate of the fluid, generating a conical shaped jet known as a Taylor cone, creating a nanodiameter fiber mat.^9,10 This process creates nonwoven mats of fiber size less than or equal to 1 µm with porous, solid, hollow, or core-shell structures in an aligned or random pattern.⁶ 

The electrospun nanofiber mat has structural and biological functions matching natural ECM properties, allowing it to act as a temporary scaffold during tissue healing, promoting cell adherence, multiplication, migration, and differentiation.² The small pore size and large surface area are beneficial for hemostasis, favorable for exudate absorption, and useful for drug loading. The porosity of the electrospun nanofibers favors cellular respiration and gas permeation while preventing the wound from drying out and dehydrating.² The nanoscale of the pore prevents microorganism invasion, ultimately inhibiting infection.² These characteristics of electrospun nanofibers address some of the underlying dysregulation in poorly healing diabetic wounds. Nanofiber dressings transform into a hydrogel-like material upon contact with moisture, providing a moist yet breathable dressing due to the nanopore size as well as the ability to absorb wound exudate. Although products exist that achieve these goals individually, no current product contains all these characteristics. Nanofiber dressings can uniquely address the needs of wound healing through the host of beneficial effects of such dressings. Adjustment of nanofiber characteristics also creates a novel opportunity to adjust properties based on patient characteristics. Ultimately, electrospinning allows for a precise attenuation of morphology, porosity, fiber diameter, drug release profiles (depending on the polymer used), voltage applied, flow rate, and collector distance.¹¹

Nanofiber application in diabetic wound healing

There is extensive literature on novel synthetic and natural polymers co-fabricated with existing or novel drugs applied to diabetic models both in vivo and in vitro. Generally, these preclinical studies show improved angiogenesis, collagen synthesis, fibroblast arrangement, and epithelialization.¹² Drugs applied in nanofiber dressings commonly include antibiotics, inflammatory modulators, natural products, and novel drugs targeting the underlying pathogenesis of impaired healing in diabetic wounds (Table).

Nanofiber dressings loaded with antibiotics aim to address the concern of treating current infection and preventing new infection—one of the primary goals in wound healing. Various antibiotics have been integrated into nanofiber dressing, resulting in adequate antibacterial properties and improved wound healing in vivo.^13-15 The modulation of release characteristics through adjustments to nanofiber fabrication specifications, polymer or polymers used, and postproduction processing make the integration of most known antibiotics simple and practical. 

Inflammatory modulators aim to address the prolonged inflammatory phase in diabetic wound healing. Alzahrani et al¹⁶ addressed the pathogenesis with a 2-fold approach involving the use of both an antibacterial modulator (fusidic acid) and an anti-inflammatory modulator (pirfenidone), resulting in accelerated wound healing. Natural polymers, including chitosan and cellulose, inherently possess antioxidant and antibacterial properties, making them beneficial for integration into nanofiber dressings used for diabetic wound healing.^14,17 The chemical properties of these natural polymers allow them to easily integrate with synthetic polymers for use in nanofiber dressings, making them a practical addition in nanofiber dressing preparations. Literature suggests that nanofiber dressings containing chitosan, synthetic polymer, and antioxidants integrated into polymer or used as the main polymer in fabrication improve wound healing with less inflammatory infiltration and increased angiogenesis.¹⁸ This mechanism allows for precision targeting of the diabetic wound pathophysiology. 

Similarly, carbohydrate and synthetic combination nanofibers have been explored because of their ability to attenuate inflammation, biocompatibility, and immune modulation. One example is the polysaccharide curdlan, which stimulates macrophage polarization to the M2 phenotype in vitro and in vivo, producing favorable wound healing characteristics in diabetic models, including mature collagen and improved vascular maturity.¹⁹ Additionally, antioxidants, including ferulic acid, cerium oxide, curcumin, and copper oxide, have been loaded into nanofiber dressings as active ingredients, resulting in accelerated wound closure, with copper oxide in particular showing upregulation of proangiogenic factors.^20-24 Inflammatory modulators target the inflammatory phase, which is essential to adequate wound healing progression and is highly dysregulated in diabetic wounds. In diabetic wounds, chronically elevated inflammation has a negative effect on wound healing, resulting in a prolonged inflammatory phase and the development of chronic wounds. The use of inflammatory modulators in nanofiber dressings has the potential to limit systemic adverse effects, decrease inflammation, and accelerate healing of diabetic wounds.

In addition, a bimodal approach utilizing drugs that target diabetic wound healing pathogenesis and nanofiber dressings facilitates an optimal healing environment. The integration of oral antidiabetic drugs pioglitazone, metformin, and glibenclamide into nanofibers has shown accelerated wound healing through improved regeneration of the dermis and epidermis, with less evidence of inflammation compared with controls.²⁵ Similarly, fabrication of nanofiber dressings with GM18, an integrin agonist, modulated fibroblast activity to improve wound healing in diabetic models in vivo.²⁶ The addition of epidermal growth factor into nanofiber dressing preparation also modulates healing through improved migration and proliferation of keratinocytes, fibroblasts, endothelial cells, and enhanced angiogenesis—vital steps in the proliferative and remodeling phases.^22,27 Importantly, the integration of living mesenchymal stem cells into nanofiber dressings creates a living wound dressing, allowing for cellular adhesion, structural wound support, and immunological cell modulation.²⁸ This methodology has been shown to improve diabetic wound healing through decreased inflammation, increased keratinocyte migration, neovascularization, and collagen remodeling.^28,29 The unique ability to easily incorporate a variety of therapeutic agents into the nanofiber dressings provides the opportunity to easily adjust treatments to create individualized dressings for patients based on specific wound characteristics. This creates the novel opportunity to provide highly specific wound care treatments.

Nanofiber wound dressings have tremendous potential to target impaired physiology in diabetic wound healing, specifically by providing an optimal environment for wound healing. The structure allows for preferred wound dressing characteristics that target the dysregulation and disruption in diabetic wounds. This nanofiber structure has the potential to incorporate immunogenic modulators to target the underlying pathogenesis to then accelerate wound healing through improved cellular proliferation, angiogenesis, and collagen deposition.

Previous in vivo and in vitro research has demonstrated improvement in diabetic wound models, warranting further investigation through clinical trials to determine the most efficacious combination of polymers and drugs.¹² Nanofiber dressings alone, without drug integration, can augment wound healing through characteristics that have a positive effect on wound healing (eg, flexibility, moist yet breathable, infection protection, acting as temporary ECM)^.2,6 The addition of novel drugs targeting wound healing pathogenesis furthers the potential to improve outcomes.⁸

Nanofiber wound dressings can address adverse effects traditionally associated with topical and oral administration of drugs.^2,30 The slow controlled release characteristics and polymer changes would allow for tunable release characteristics unique to patient needs, drug properties, and prevention of adverse effects.³⁰ The ease of fabrication of nanofibers allows for the creation of unique dressings to address the needs of individual patients.⁶ Ease of modulation of nanofiber dressing characteristics opens new possibilities to tailor wound dressings for individualized wound care. Adjusting wound dressing specifications to meet individual needs has potential to accelerate wound healing, decrease health care spending, and improve quality of life, especially in the difficult to manage and burdensome disease state of diabetic wound healing. 

Nanofiber dressings have the potential to reduce health care spending through decreased health care costs secondary to hospital stays, amputations, and chronic wound care, making the use of nanofiber dressings advantageous compared with standard dressings. For nanofiber dressing to be clinically feasible, the up-front cost of dressings must be low enough to justify the price, and risk reduction of complications must be both clinically and statistically significant. Currently, a cost-effectiveness analysis is not possible due to the lack of nanofiber wound dressings on the market. In future studies, such analysis will be important as nanofiber wound dressing products become available. The multitude of in vivo and in vitro studies showing promising results in diabetic models provide evidence that further investigation into nanofiber dressings is warranted.¹² Importantly, the poor clinical outcomes with the current standard of care for diabetic wounds emphasizes the need for investigation into improved treatments.^31,32 

The aforementioned features of nanofibers and the vast need for an improved standard of care for diabetic wounds underscore the importance of further studies on nanofiber wound dressings, specifically randomized controlled trials.^31,33-35 There is also an impetus to experimentally compare different drug types loaded into nanofiber scaffolds to determine which therapeutic approaches have superior promise and efficacy in improving wound healing.³⁶ Advancing nanofiber wound dressings toward clinical adoption requires collaboration between researchers, regulatory agencies, and collaborative public and private partnerships providing funding. Future studies should be adequately powered and should focus on the clinically meaningful end points, including wound closure time, infection rates, hospitalization rates, amputations, and, importantly, patient-reported quality of life outcomes. This process could be accelerated through the standardization of fabrication processes and nanofiber dressing benchmarks to facilitate reproducibility and improve comparisons across studies. With the potential for a high-impact improvement in patient care, collaboration between researchers and regulatory bodies (eg, US Food and Drug Administration) to clarify required safety and efficacy data for this emerging technology would remove another barrier to moving this technology to the next phases. Finally, increased investment from federal organizations, support from the American Diabetes Association, and public-private partnerships would provide valuable resources to accelerate this translational research, particularly given the high clinical need and potential for cost savings.

This scoping review has limitations. Most of the studies included in this review are preclinical, which may not fully represent outcomes in human diabetic wound healing. Similarly, polymer type, fabrication methods, and evaluation metrics vary between studies, which limits direct comparison between studies. These studies may also be influenced by publication bias favoring positive outcomes and the lack of long-term longitudinal data. Finally, the narrative scoping nature of this review limits comprehensiveness and reproducibility. 

Chronic diabetic wounds place a significant burden on health care spending and patient quality of life, while disproportionately affecting underresourced groups. Lack of adequate treatments addressing the underlying pathogenesis of diabetic wounds and high complication rates make further research into wound dressings essential to improving morbidity and mortality of patients with diabetes. 

Nanofiber wound dressings offer a solution to the difficulties of traditional wound dressings through incorporation of drugs targeting underlying pathophysiology, customizable features, and immunologically desirable characteristics. Current evidence in diabetic models suggests that nanofiber wound dressings accelerate wound contraction, thus providing support for future randomized controlled trials to assess the wound healing potential of this technology. Although up-front costs may be cost prohibitive, nanofiber wound dressings provide a solution to the substantial problem of impaired healing in patients with diabetes.