Diabetes is an epidemic disease with increasing prevalence and alarming burden, which has become a major global public health problem [1]. Chronic diabetic wounds seriously threaten the prognosis and life quality of patients [2]. Accumulating evidences have indicated that excessive reactive oxygen species (ROS) aggravate the oxidative stress and impede angiogenesis of diabetic wound, resulting in immune imbalance and a prolonged inflammatory phase in lesion [3, 4]. Furthermore, impaired vessel formation restricts the diffusion of nutrients and oxygen, causing persistent hyperglycemia, hypoxia, and subsequent bacterial infection [5]. ROS produced by bacterial infection further impede angiogenesis and macrophage function, thus accelerating and aggravating the pathological changes of wounds [6]. The aforementioned factors make diabetic wounds different from the normal wound healing and easy to form long-lasting unhealed chronic wounds [7]. Therefore, designing of wound dressing with effective ROS scavenging and antibacterial functions is of great importance in refractory diabetic wound management.

Up to now, various wound dressings have been developed, such as semi-permeable membranes, semi-permeable foams, hydrocolloids and hydrogels [8]. Among them, injectable hydrogels have been widely accepted as the most attractive wound dressings, because of its high moisture retention, wound exudate absorption and oxygen permeability, as well as shape adaptability to cover irregular wounds [9, 10]. Hydrogel dressings have exhibited obvious therapeutic effects in various skin wound models [11, 12]. However, due to the inadequately mechanical strength and self-healing ability, normal body movement or local stress could hinder the function of hydrogel dressing and expose the wound to external infection risk again [13]. More importantly, the vulnerability of lacking tissue adhesion makes the hydrogels unable to attach to the wound tightly [14]. Incorporating functional ingredients contributes to the preference of multifunctional hydrogel. For instance, hydrogels containing natural polyphenols, such as gallic acid, tannic acid, resveratrol, epigallocatechin gallate, exhibit strong ROS scavenging, tissue-adhesive, self-healing, and inherent antimicrobial capabilities [15], [16], [17].

Bacterial infection is one of the biggest factors slowing down wound healing, especially for chronic diabetic wounds. Specifically, it can cause severe infection-related complications such as sepsis, acute renal failure, and even death [18, 19]. Many efforts have been attempted to address this major challenge. Active ingredients including antibiotics, antibacterial peptides, silver ion or nanoparticles, and nano-enzymes offer viable options for fighting the biofilm infection [20, 21]. Unfortunately, these methods also brought other issues, such as drug resistance, side effects, complicated fabrication and high cost [22]. Photothermal therapy (PTT), emerged as a new alternative treatment, has gained much attention for its effective microbial removal [23]. Especially, the PPT induced by near-infrared light (NIR) can absorb NIR and convert the light energy into heat energy, resulting in the denaturation of bacterial proteins and eventually death of irradiated bacteria [24]. Due to its remote controllability, deep tissue penetration, minimal invasion, tissue regeneration promotion and reduced drug resistance, PPT has been regarded as one of the most promising antibacterial methods [25, 26]. Moreover, PTT has also shown an attractive approach for local heating owing to its high inherent specificity and low invasion burden [27]. It has been further demonstrated that PPT could promote the wound healing process by accelerating blood flow in the wound area, stimulating fibroblast proliferation and reducing inflammation [28, 29]. A variety of smart materials with NIR response have been developed, such as noble metal nanoparticles, nonmetallic compounds, and carbon-based nanomaterials [30], [31], [32]. However, these materials are compromised by their high cost, cumbersome manufacturing process, low photothermal conversion rate, as well as potential cytotoxicity [33]. Recently, the chelates of Ferric ion and polyphenol have been explored and showed an advantage in their high NIR photothermal conversion efficiency, facile fabrication, good economic benefit and biocompatibility [34].

Herein, a multifunctional hydrogel dynamically double-crosslinked by Schiff-base bonds and metal coordination bonds was developed as novel dressing for diabetic wound treatment (Scheme 1). The prepared hydrogel has the characteristics of injectability, self-healing, adhesion, biodegradability, biocompatibility, especially the NIR-photothermal antibacterial activity and ROS scavenging capability. Based on these above superiorities, this hydrogel wound dressing effectively close the wound and accelerate the healing process of infected diabetic wound in a mouse model. Results of H&E, Masson's trichrome and immunofluorescence staining demonstrated that such multifunctional hydrogel could ameliorate inflammation and reduce oxidative stress, remove infection with NIR radiation, promote angiogenesis, and thereby exhibiting a huge potential in the diabetic wound management.