# Biohydrogel Based on Dynamic Covalent Bonds for Wound Healing Applications
## 1 Introduction  
When the body is injured, it activates a sequence of processes to heal, entailing hemostasis, inflammatory, proliferative, and maturation phases [1]. Synthetic biomaterials around the wound can regenerate and heal after damage via sealing or reparative processes. This process may involve the presence of sacrificial bonds between molecules which break and reform, allowing improved adaptation of the material to external conditions [2, 3], or may involve the release of encapsulated sealing agent [4]. Dynamic covalent chemistries offer interesting paths for the preparation of soft materials that offer the advantages of both strength and reversibility [5]. These dynamic materials are affected by external conditions, including pH and temperature, as well as compositional variables, such as concentration; thus, these materials are stimulus responsive [6]. Among different dynamic bonds [5], B-O bonds constitute one of the most versatile examples because their dynamic behavior in trigonal planar boronic ester can be achievedin numerous ways, including hydrolysis/dehydration, transesterification, or metathesis reactions [6]. In particular, the reversible condensation reactions between derivatives of boronic acid and _cis_-1,2 or _cis_-1,3 diols (polyols) to form cyclic esters have been explored to create self-healing materials at room temperature [7; 8]. Another advantage of the B-O dynamic bonds has been ascribed to their role in the modulation of cell attachment and differentiation by using dynamic platforms in the presence of phenylboronic acids, which can interact with cell surface polysaccharides [9]. These qualities of dynamic B-O bonds have been applied for tissue engineering and drug delivery [10]. Moreover, natural polysaccharides such as sodium alginate can be conveniently functionalized with covalent bonds [11] to form biodegradable and biocompatible [12] self-healing soft materials [13; 14] with biomedical potential. On the other hand, nanocomposites involve mixtures of materials in which at least one physical dimension is reduced to the nanoscale range [15]. In particular, nanocomposite hydrogels are basically hydrated polymeric networks containing nanomaterials, which appear to have unique properties different from those of the individual constituents. Indeed, composite hydrogels contain multifunctional entities that can improve efficiency of the polymeric network. The properties of these heterogeneous and reinforced matrices are affected by the constituents and their properties, structure, and interfacial interactions [16]. Within this context, inorganic materials such as silicates show a high aspect ratio and are being increasingly used for the preparation of nanocomposites with enhanced properties, which are mainly attributed to the many surface interactions of polymeric networks and silicate particles [17]. Thus, the combination of silicate particles with hydrogel networks based on B-O bonds could also provide a versatile approach to modulate the functional properties of the gels. Wounds resulting from physical, chemical, or thermal agents can become infected if left open, leading to a need to achieve rapid wound closure. Wound healing processes entail cellular and biointerfacial interactions, involving fibroblasts, keratinocytes, and endothelial cells [1], whose mobilization and arrangements may be influenced by certain biomimetic materials. Different stages of wound healing occur in sequence, and hydrogels can affect any of the steps. Provision of a dynamic scaffold to facilitate regeneration of cells at wound site may enhance wound closure. Hydrogels can help maintain the necessary moist wound environment and their physico-mechanical properties are similar to those of soft tissues, making them compatible at the site of action. Furthermore, hydrogel materials may be useful in chronic cases where the pH of the wound zone increases, becoming alkaline.