Wound management and healing remain as a global clinical and scientific challenge. Therefore, the development of advanced wound dressings is an active field of research, and several products have been recently introduced to promote healing in patients [1]. An ideal wound dressing should meet specific criteria, which include being biocompatible, maintaining local moisture, avoiding microbial contamination, having sufficient mechanical strength to maintain its integrity during its use, and allow an easy removal [2]. In this context, hydrogels have gained popularity due to their outstanding mechanical and biochemical properties, and nowadays represent one of the most commonly used dressings in clinical practice [3].

Compared to other dressings, such as gauzes or synthetic films, which attempt to avoid further complications by providing a temporary barrier to wounds, hydrogels have attracted increased clinical attention, as they can provide an optimal physiological microenvironment, accelerating the process of wound healing [4]. Another advantage of using hydrogels is that they can be easily modified in order to meet the specific requirements of diverse wounds. Therefore, parameters such as composition, moisture, pore size or mechanical strength can be optimized based on the type of the wound [3,5]. Hydrogels can be further activated by incorporating bioactive molecules, including therapeutical drugs [6,7], antimicrobial agents [8,9], and growth factors [10,11] which can be locally released providing a customizable platform to improve wound healing. The release of these biomolecules can be further controlled based on the mechanical properties and pore size of the hydrogels, where larger pores will enable a more rapid molecule release [2]. Moreover, hydrogels can be easily applied onto irregular and deep wounds due to their flexibility and ability to crosslink in situ [12]. Finally, excess exudate, metabolic waste products, and proinflammatory molecules that are present in the surface of the wounds can be absorbed by these dressings, which can then be easily removed and replaced, acting as cleaning systems and enhancing autolytic debridement [13].

Among the key molecules of the wound healing process, oxygen is described to be crucial in its success, being involved in several critical steps including aerobic cell metabolism, angiogenesis, collagen maturation, and oxidative killing of bacteria [14,15]. Although it has been well described that despite acute hypoxia acts as an initial signal to promote wound healing, prolonged and chronic hypoxia plays a major role in non-healing chronic wounds [16]. Hence, several efforts have been made to provide oxygen to wounds either systemically or locally, including hyperbaric oxygen therapy (HBOT) or topical oxygen therapy (TOT), but larger studies are still needed, as no consistent or significant results have been obtained [16], [17], [18]. In addition, dressings have been designed to deliver oxygen in the wound site by incorporating different chemical compounds such as hydrogen peroxide, calcium peroxide or perfluorocarbons, representing a promising approach for the local oxygenation of wounds [19]. However, these artificial oxygen carriers present several limitations, including local toxicity, poor stability, and short term oxygen delivery [20].

Recently, the use of photosynthetic microorganisms has been suggested as an alternative approach to increase local oxygen concentration in several medical fields including antitumor therapies [21], [22], [23], [24], stroke and ischemia treatment [25], [26], [27], [28], organ preservation [29,30], and wound healing [31], [32], [33], [34], [35]. In the case of wound healing, scaffolds containing Chlamydomonas reinhardtii microalgae cells have shown to decrease tissue hypoxia in vitro [31], and further studies have shown their safety in both, animal models [36], and human patients [37]. Moreover, the generation of genetically engineered photosynthetic microalgae and cyanobacteria has been studied, aiming to additionally provide freshly produced recombinant bioactive molecules in situ, such as growth factors [34,36] and glycosaminoglycans [38].

Taking all this into consideration, in this work a biocompatible photosynthetic hydrogel-based wound dressing was developed to release oxygen as well as other bioactive molecules to wounds.