Research indicates that 19–34 % of diabetic patients are at risk of developing foot infections, which may progress to intractable chronic ulcers and deep tissue damage [1]. These severe complications often necessitate lower extremity amputation, resulting in significant physical disabilities and profound psychological distress that severely compromises quality of life. In clinical practice, infection control and promoting wound healing are two primary priorities for managing diabetic wounds. Current clinical treatments include surgical debridement [2,3], application of wound dressings [4,5], and administration of systemic or local antibiotics [6,7]. Despite these interventions, the prognosis remains unsatisfactory due to persistent ischemia, hypoxia, and recurrent bacterial infections. The complex pathological characteristics of diabetic wounds urge the development of innovative multifunctional therapeutic strategies capable of simultaneously inhibiting bacterial growth, scavenging reactive oxygen species (ROS), and restoring neovascularization.

The insufficient vascularization in diabetic wounds significantly restricts their healing rate. Therefore, promoting the proliferation of endothelial cells and fibroblasts within these wounds can effectively accelerate the healing process [8]. Recently, membrane-enclosed apoptotic bodies (Abs) generated during cell apoptosis have attracted increasing attention as a novel type of extracellular vesicles [9,10]. Studies have demonstrated that Abs can promote the proliferation of endothelial cells and enhance vascularization [11,12], exhibiting significant efficacy in wound healing and tissue regeneration. Moreover, Abs exhibit phosphatidylserine (PS) expression on their surface, which facilitates the specific recognition by phagocytes. This recognition subsequently induces the transformation of phagocytes into M2 anti-inflammatory phenotypes, thereby alleviating the inflammatory environment [13].

One of the critical strategies for promoting diabetic wound healing is to improve the hypoxic environment by restoring continuous oxygen supply [14]. Nanozymes, engineered as artificial enzymes with catalytic properties mimicking natural enzymes, exhibit remarkable enzyme-like activity and robust stability in redox homeostasis regulation [15]. These attributes have driven their adoption across diverse applications in the treatment of various diseases including inflammation [16], cancer [17], and Alzheimer's disease [18]. Accumulating evidence demonstrates that MnO2 nanozymes possess both superoxide dismutase (SOD) and catalase (CAT) activities. This dual enzymatic activity allows effective elimination accumulated ROS in diabetic wounds, leading to significant oxidative stress mitigation [19]. Furthermore, MnO2 nanozymes catalyze H2O2 decomposition for O2 generation, directly addressing wound hypoxia [20,21]. Additionally, the acidic microenvironment of inflammation triggers MnO2 dissociation into Mn2+ ions, which exhibit broad-spectrum antibacterial properties [22,23].

In situ forming gels can be administered as solutions or suspensions and undergo rapid sol-to-gel transformation in response to physicochemical stimuli, such as changes in pH or temperature [24,25]. Temperature is the most widely employed physiological stimulus to induce the phase transition. Thermosensitive in situ gels have been specifically developed to form gels upon exposure to skin surface temperatures ranging from 30.51 to 35.09 ℃ [26]. Poloxamer 407 (P407) is one of the most widely used thermosensitive materials, characterized as a triblock copolymer consisting of a central hydrophobic block of polypropylene glycol (56 repeat units, 30 % w/w) and two flanking hydrophilic blocks of polyoxyethylene (101 repeats each, totally 70 % w/w) [27]. Thermosensitive hydrogels based on P407 (TSCG 407) exhibit fluid-like behavior at room temperature but undergo a phase transition to form more viscous gels at body temperature [28]. Consequently, this temperature-responsive gelling system enables prolonged localization and wound coverage to the irregular shapes of diabetic wounds, effectively controlling and prolonging drug release.

The main aim of the present investigation was to develop a sprayable and thermosensitive in-situ forming composite gel based on P407 to achieve optimal therapeutic effects for diabetic wound healing. The composite gel was prepared by incorporating polyvinyl alcohol 0588 (PVA 0588) and polyvinylpyrrolidone K30 (PVP K30) into the thermosensitive gelling solution formulations containing poloxamer 407 (14 %, w/v), with the aim of improving the bioadhesiveness and water permeability. HUVECs derived Abs (H-Abs) were isolated and camouflaged MnO2 nanozymes to obtain BM@H-Abs. Finally, BM@H-Abs was evenly mixed with TSCG-P407 to form the composite BM@H-Abs/TSCG-P407.

Scheme 1 illustrates the synthesis process and therapeutic potential of BM@H-Abs/TSCG-P407. This sprayable in situ forming gel demonstrates the ability to adaptively cover irregular wounds, prolong drug retention, and minimize liquid drug loss. The encapsulated H-Abs and BM may contribute synergistically to wound healing by promoting endothelial cell proliferation and restoring oxygen supply. Additionally, BM exhibits potential for ROS scavenging and bacterial growth inhibition. Collectively, this multifunctional system may mitigate pathological hypoxia, accelerate tissue regeneration, and represent a promising therapeutic strategy for diabetic wounds management.