**4. Management of wounds through nanotherapeutic approaches**

As described above, wound healing is a dynamic and highly regulated process. Wound closure can be realized by either regeneration or repair. The process of healing has been described as a playing orchestra where an organized interplay of various factors, such as cells, cytokines, and growth factors, leads to tissue repair [55]. However, when this intricate balance gets disrupted, the healing process is affected with recent reports suggesting that the absence of a particular cell or a mediator gets compensated so that the tissue repair process goes on [42]. The currently used wound management strategies have certain limitations in fulfilling the needs of comprehensive care [62]. Hence, wound healing remains a challenge and a burden [63]. The treatment modalities in practice are specifically based on the type of wounds, with inadequate management leading to complications such as chronic wounds, fibrosis, compromised tissue functioning, or even amputation [64]. The best prevention technique against undesirable outcomes during healing is the effective management during the early stages of the process to prevent wounds to progress to chronic conditions.

Recent advances in interdisciplinary research have brought bioactive materials to the forefront as smart wound care materials [8, 65]. Bioactive materials can potentially be exploited to target any phase of the healing process by their direct cellular interactions or indirectly through ECM. Biopolymers are one of the most widely exploited bioactive materials used for wound care because they possess useful properties such as ability to support cell growth, biocompatibility, biodegradability, durability, and regenerative potential [66]. Dermal substitutes and human skin equivalents are the two food and drug administration (FDA)-approved biomaterial therapies promoting healthy healing *via* their interaction with the wound microenvironment [67–70]. Due to the increased understanding of the healing process, there has been an emergence of dressing-based wound-healing materials [71]. Modern dressings have been designed for successful healing by providing a beneficial wound microenvironment with control on moisture and absorbance of excess exudates. Active dressings

have been known to alter the wound microenvironment *via* targeting microbial load and excessive proteases or aiding tissue growth by alginate, chitosan, hyaluronan, and collagen matrices acting as scaffolds [72–74]. There have been plenty of reports that demonstrate the advantages of modern dressings harboring cells and recombinant growth factors, but still, the majority of the clinical modalities are based on safety evaluation rather than efficacy [75].

Chronic wounds demand very robust and efficacious therapies that address the various challenges of a deregulated healing process. Many of the novel approaches have failed in delivering specific healing outcomes, which have further made way for the introduction of several nanotechnology-based wound-healing therapies [7]. The chronic nature and associated complications of nonhealing wounds have led to the emergence of nanotechnology-based therapies for ultimately repairing the injured tissue [65]. Multitudes of nanotherapeutic approaches have been introduced to efficiently manage the wounds and remove any related possible complications (**Figures 2** and **3**) [76]. The advantage of using nanomaterials over other wound dressings is their tenability, low cytotoxicity, good biocompatibility, drug delivery ability, and versatility of physicochemical properties endowing them with many unique features [71, 76, 77]. Furthermore, nanoscale helps them in enhanced penetration to the injury site and a high interaction probability with the biological target [78]. Consequently, NPs possess the ability of controlled and sustained the release of therapeutics, resulting in accelerated wound repair [72].
