Ashokrao Mane College of Pharmacy Peth Vadgaon.
Wound healing research has led to innovative biomedical approaches, enhancing treatment outcomes. Key strategies include ¹ ²: - Biomaterial-based approaches: Utilizing hydrogels, nanofibers, and scaffolds to promote tissue regeneration and wound closure. Examples include fibrin hydrogel with gelatin, glycerol, and hyaluronic acid, and chitosan/collagen blended nanofibers. - Stem cell therapies: Leveraging adipose-derived stem cells, bone marrow-derived mesenchymal stem cells, and their exosomes to enhance angiogenesis, re-epithelialization, and tissue repair. - MicroRNA-based therapies: Targeting specific microRNAs, such as miR-21, miR-31, and miR-132, to regulate wound healing processes like inflammation, angiogenesis, and re-epithelialization. - Nanoparticle-based treatments: Employing nanoparticles loaded with growth factors, antibiotics, or other therapeutic agents to promote wound healing and prevent infection. - 3D bioprinting and biofabrication: Creating personalized skin substitutes and scaffolds to facilitate wound healing and tissue regeneration. These approaches aim to improve wound healing outcomes by promoting tissue regeneration, reducing inflammation, and preventing infection.
1.1 Wound healing: Wound healing is a complex process involving interactions among a variety of different cell types. The normal wound repair process consists of three phases- inflammation, proliferation, and remodelling that occur in a predictable series of cellular and biochemical events. Wounds are classified according to various criteria: etiology, lasting, morphological characteristics, communications with solid or hollow organs, the degree of contamination. In the last few years many authors use the Colour Code Concept, which classifies wounds as red, yellow and black wounds. [1]
1.2 The process of wound healing typically involves several overlapping phases:
Fig.1: Phases of wound healing [2]
1.2.1 Hemostatis: Hemostasis is the first stage in wound healing that can last for two days. As soon as there is a wound on the body, the blood vessels in the wound area constrict to reduce the blood flow. This is known as vasoconstriction. At the same time, clotting factors are released at the wound site to coagulate with fibrin, resulting in a thrombus, which is more commonly known as a blood clot. The clot acts as a seal between the broken blood vessels to prevent blood loss. [3]
1.2.2 Inflammatory Phase: The second phase of wound healing is called the Inflammatory Phase. It involves phagocytic cells that release reactive oxygen species, lasting for up to seven days in acute wounds and longer in chronic wound [4]. During this phase, white blood cells and some enzymes enter the wound area to stave off infection by clearing bacteria and debris and preparing the wound bed for new tissue growth. Physical characteristics of the phase include inflammation or redness at the wound site, edema, heat, and pain.During Phase 2, a type of white blood cells called neutrophils enter the wound to destroy bacteria and remove debris. These cells often reach their peak population between 24 and 48 hours after injury, reducing greatly in number after three days. As the white blood cells leave, specialized cells called macrophages arrive to continue clearing debris. These cells also secrete growth factors and proteins that attract immune system cells to the wound to facilitate tissue repair. This phase often lasts four to six days and is often associated with edema, erythema (reddening of the skin), heat and pain. [5]
1.2.3 Proliferative Phase: Once the wound is cleaned out, the wound enters Phase 3, the Proliferative Phase, where the focus is to fill and cover the wound. The Proliferative phase features three distinct stages: 1) filling the wound; 2) contraction of the wound margins; and 3) covering the wound (epithelialization). During the first stage, shiny, deep red granulation tissue fills the wound bed with connective tissue, and new blood vessels are formed. During contraction, the wound margins contract and pull toward the center of the wound. In the third stage, epithelial cells arise from the wound bed or margins and begin to migrate across the wound bed in leapfrog fashion until the wound is covered with epithelium. The Proliferative phase often lasts anywhere from four to 24 days. [6]
1.2.4 Remodeling Phase: Scar tissue formation characterizes the final Remodeling Phase (also known as Maturation). It may occur over months or years, depending on the initial severity of the wound, its location, and treatment methods. During this phase, the new tissue gradually becomes stronger and more flexible. Collagen production continues to build the tensile strength and elasticity of the skin. The build-up of collagen in the granulation tissue leads to scar tissue formation, which is 20 percent weaker and less elastic than pre-injured skin.the new tissue slowly gains strength and flexibility. Here, collagen fibers reorganize, the tissue remodels and matures and there is an overall increase in tensile strength (though maximum strength is limited to 80% of the pre-injured strength). The Maturation phase varies greatly from wound to wound, often lasting anywhere from 21 days to two years. The healing process is remarkable and complex, and it is also susceptible to interruption due to local and systemic factors, including moisture, infection, and maceration (local); and age, nutritional status, body type (systemic). When the right healing environment is established, the body works in wondrous ways to heal and replace devitalized tissue.[7]
1.3 Types of wound Healing
Fig.2 Types of wound healing [8]
Primary wound healing
1.3.1 Primary wound healing: occurs when a wound is closed within 12–24 hours of its creation (e.g. clean surgical incision, clean laceration). The wound edges are approximated directly using sutures, tissue glue, tapes or a mechanical device.The incision causes only focal disruption of the continuity of the epithelial basement membrane, and the death of a relatively few epithelial and underlying connective tissue cells.As a result, epithelial regeneration predominates over. Primary wound healing, or primary intention wound healing, refers to when doctors close a wound using staples, stitches, glues, or other forms of wound-closing processes.Closing a wound in this way reduces the tissue lost and allows the body to focus on closing and healing a smaller-area wound rather than the larger initial wound.For example, a doctor might stitch up a large cut rather than allow the body to heal over the entire cut.[8]
1.3.2 Secondary wound healing: Secondary wound healing, or secondary intention wound healing, occurs when a wound that cannot be stitched causes a large amount of tissue loss. Doctors will leave the wound to heal naturally in these cases. This may be more common for wounds that have a rounder edge, cover uneven surfaces, or are on surfaces of the body where movement makes stitches or other closure methods impossible. Secondary wound healing relies on the body’s own healing mechanisms. This process takes longer, which may be due to increased wound size, the risk of infection and contamination, and other factors, such as the use of certain medications In this type of healing, a full-thickness wound is allowed to close and heal. Secondary healing results in an inflammatory response that is more intense than with primary wound healing. In addition, a larger quantity of granulomatous tissue is fabricated because of the need for wound closure. Secondary healing results in pronounced contraction of wounds. Fibroblastic differentiation into myofibroblasts, which resemble contractile smooth muscle, is believed to contribute to wound contraction. These myofibroblasts are maximally present in the wound from the 10th-21st days.[8]
1.3.3 Tertiary wound healing: Tertiary wound healing, or healing by delayed primary closure, occurs when there is a need to delay the wound-closing process. This could be necessary if a doctor fears that they may trap infectious germs in a wound by closing it. In these cases, they may allow the wound to drain or wait for the effects of other therapies to take place before closing the wound. In tertiary intention healing, there is a need for the wound to be open for a period of time before it can be sutured. Examples can be a wound left open to allow drainage and later is closed or a wound that is left to heal by secondary intention but encounters complications, where after a very thorough debridement is performed followed by an approximation of the wound edges. [8]
1.4 Types of wounds
There are several types of wounds, depending on factors such as the source of the wound and any underlying issues that may lead to it. The type may alter how doctors treat the wound or other factors in the healing process.Wounds are typically open or closed. A closed wound is an injury that does not break the surface of the skin but causes damage to the underlying tissues. A bruise is a common example of this. On the other hand, open wounds break the surface of the skin and may also damage underlying tissues. [9]
Some types of open wounds include:
Chronic wounds may also cause breakages in the skin that need to heal. These include bedsores, other pressure injuries, and diabetes-related ulcers. [10]
Fig.3: Type of wounds [11]
1.5 The role of Physiological factors and antimicrobial agents in wound healing: Growth factors play a role in cell division, migration, differentiation, protein expression, enzyme production and have a potential ability to heal wounds by stimulating angiogenesis and cellular proliferation, affecting the production and the degradation of the extracellular matrix, and by being chemotactic for inflammatory cells and fibroblasts. There are seven major families of growth factors: epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), interleukins (ILs), and colony-stimulating factor (CSF). Acute wounds contain many growth factors that play a crucial role in the initial phases of wound healing. The events of early wound healing reflect a finely balanced environment leading to uncomplicated and rapid wound healing. Chronic wounds, for many reasons, have lost this fine balance. Applications of some drugs (antioxidants--asiaticoside, vitamin E and ascorbic acid; calcium D-pantothenate, exogenous fibronectin; antileprosy drugs--oil of hydnocarpus; alcoholic extract of yeast) accelerate wound healing. Thymic peptide thymosin beta 4 (T beta 4R) topically applicated, increases collagen deposition and angiogenesis and stimulates keratinocyte migration. [12] Thymosin alpha 1 (T alpha 1R), peptide isolated from the thymus, is a potent chemoattractant which accelerates angiogenesis and wound healing. On the contrary, steroid drugs, hemorrhage and denervation of wounds have negative effect on the healing process.
1.6 VARIOUS APPROACHES FOR WOUND HEALING:
1.6.1 Skin Grafts: Skin grafts are used when wounds have sustained a large amount of tissue loss by trauma or chronic ulceration. The grafts can be classified into split-thickness skin grafts (STSGs) and full-thickness skin grafts (FTSGs) according to the thickness. STSGs can guarantee the cutaneous covering for practically any defect, and is regarded as the surgical standard of care for various types of wounds. Atypical STSG involves harvesting the epidermis and superficial dermis from healthy skin but not the whole dermis. However, limitations still exist with this method. When skin loss of a patient exceeds 30% of the total body skin area (TBSA), skin is not available in sufficient quantity for an STSG. Skin grafts can also be classified as autografts, allografts and xenografts based upon the donor origins. [13]
Fig.4: Skin Grafts [14]
1.6.2 Wound dressing: The ideal wound dressing must possess the following characteristics: providing wound protection, ability to remove excess exudate, anti-microbial properties, maintaining a humid environment, high permeability to oxygen, easy removal from the wound site and non-anaphylactic characteristics[15]. The most commonly used materials are as follows.
Fig.5: Wound Dressing [17]
1.6.3 Vacuum assisted skin substitutes : VAWC dressing utilizes a closed and sealed system to place negative pressure on a surface and thus produces traction of soft tissues and diminishes the surface and depth of the injury Patients who received VAWC within 3 months of ulcer onset had a greater likelihood of wound healing than those who received VAWC 1 year or later after onset. VAWC can observably diminish water loss of the STSG area, shorten healing time. and duration of hospital stay and lower the recurrence of infection during wound healing. [18-19]
Fig.6: Vacuum assisted skin substitutes [20]
1.6.4 Engineered skin substitutes : The three major components of currently available ESSs are scaffold materials, growth factors and cells. Exploration of ESS was started from the success in cultivating epithelial cells. However, substitutes simply composed of epidermis are fragile and least efficient in both antimicrobial activity and promotion of wound contraction . As a result, epidermal ESSs are not widely used in clinical practice and current commercialized ESSs are mostly dermal substitutes or substitutes with both epidermis and dermis. Commonly used dermal substitutes include Integra, Alloderm, Dermagraft, Biobrane, Permacol, Dermacell, Transcyte and Matriderm. Alloderm is a good option for treating major burns to prevent scar formation and loss of joint function, whereas Dermacell is an appropriate adjunct to breast reconstruction. Similar to Dermacell and Alloderm, Permacol is based on aporcine acellular dermal matrix but with the combination of hexamethylene dissocyanate. [21-22] Overall, ESS shows potential in treating different types of acute and chronic skin wounds, as is mentioned above. Nowadays, developments in science and technology contribute to the promise of ESSs. For example ,base on the need for diverse therapeutic factors at different healing stages, a novel textile dressing, which utilizes composite fibers to release different drugs in a controlled temporal profile at different stages of healing, was developed .In addition, scientists have shown that topical application of artificial spider silk, which is able to control the delivery of drugs, significantly accelerates the process of skin reconstruction and re duces wound surface area in vitro.[23-24]
1.6.5 Stem cell therapy: To optimize wound healing, ESS can be used in combination with stem cell therapy. Stem cells are attractive for cell-based therapies because of their capacity for self-renewal and differentiation. For the past few years, advances in stem-cell biology have given hope for treatment of chronic wounds that cannot be healed with conventional therapy. stem cells can be defined as pluripotent (can give rise to any specialized cells in the humanbody) andmultipotent (can give riseto manybut not all cell types). Embryonic stem cells (ESCs; pluripotent) and adult mesenchymal stem cells (MSCs; multipotent) are two common and promising populations of stem cells used in both laboratory studies and clinical therapy.[25-28] In order to improve the effectiveness of stem cell therapy, scaffold-based therapeutic strategies, e.g., use of a decellularized silk fibroin scaffold or a nanoscaffold, have been used to preserve cell function and improve healing . Matrigel, a gelatinous protein mixture secreted by mouse sarcoma cells, with Matriderm, an ESS mentioned above, are both excellent matrices for delivery of MSCs . A microsphere-based engineered skin with murine BM-MSCs and epidermal growth factors achieved a higher rate of wound repair, thicker granulation tissue and better vasculature, when compared with that without growth factors in vitro. These studies suggest that a scaffold-based de livery system with the addition of growth factors might achieve better effects when applying stem cells. [29-31]
Fig.7: Stem cell therapy [32]
1.6.6 Growth factor and cytokines: Growth factors and cytokines are biologically active proteins that can control all stages of the wound-healing process. Although shown to have noticeable benefits, growth factors and cytokines have stability problems due to proteases present at the wound site. However, incorporation of growth factors within a fibrin biomatrix has been shown to prolong growth factor stimulation at wound site. Scaffolds with hyaluronic acid and slowly released growth factors have also been shown to promote the recovery of skin wounds.[33-35]
There are other innovative approaches that can improve wound healing. For debridement, non-contact, low frequency ultrasound therapy, which separates denatured protein, directly kills surface bacteria and increases blood flow, can improve healing rates of venous leg ulcers. Hydrosurgical debridement using a razor-thin saline jet can reduce both operative times and intraoperative blood loss, compared to traditional debridement techniques. [36-38]
1.6.7 Cell therapy : Cell delivery, which in this regard is described as transporting either skin or vascular cells to the site of injury, has attracted much attention in the acceleration of regenerative wound healing. Among the different cells, stem cells, due to their potential to differentiate into several cell types and self-renewal properties, have been suggested specially for the treatment of chronic and non-healing wounds. The majority of the cells are used for skin regeneration, including adipose derived stem cells (ADSCs), MSCs, endothelial progenitor cells (EPCs), induced pluripotent stem cells (iPSCs).It should be noted that low cell viability is one of the main problems in conventional cell therapy . In order to address this problem, cell delivery within hydrogels and cell imprinting are suggested as an alternative cellular approach to achieve better healing. Using bioprinting and modified laser induced forward transfer technologies; it is possible to make a 3D skin graft . Koch et al. used a laser assisted method to print fibroblasts and keratinocytes embedded in collagen gel, layer by layer. After 10 days of culturing, cells proliferated and showed high viability, making an integrated graft with tight cellular junction. [39-43]
Fig.8: Cell therapy
1.6.8 Bioactive Therapeutic Delivery : An ideal carrier for bioactive therapeutic delivery should be biocompatible, biodegradable, non-cytotoxic, and easy to fabricate by tailoring the physical/chemical properties. Till now, therapeutics have been loaded into different nano/micro carriers such as fibers, spheres, capsules, sheets, rods, and dot arrays. These carriers can be produced in form of core shell structures with the benefit of storing the drug in the core cavity, while modifying shell composition (polymers or lipids) to adjust the release pattern.[44]
The vast lists of drugs known to have antibacterial, regenerative, and angiogenic effects from natural bioactive and biochemical therapeutics have been used in wound healing treatments. For example curcumin, berberine, rosemary oil, thyme extract, Aloe vera, and honey, as natural agents, and gentamicin, tetracycline hydrochloride, vancomycine, melatonin, simvastatin, and erythropoietin as chemical agents, can be suggested.[45-46]
1.6.9 Gene Therapy : Skin is considered as a suitable target for delivery of genetic-based therapeutics, due to the readily attainable anatomical position for gene transfer and visually observable therapeutic effects. Among several studies performed for skin gene therapy, those encapsulated into the nano/ micro carriers, tissue scaffolds, or even using genetic manipulated cells are more prosperous regarding their potential to both protect genetic based therapeutics from enzymatic degradation and improve their healing effects.In addition, several studies are aimed to use siRNAs as therapeutics for selective inhibition of MMP, fibrotic tissue growth factors, inflammatory cytokines, p53, and also prolyl hydroxylase domain (PHD) proteins to induce fast healing and angiogenesis in specially chronic and non-healing wounds. [47]
Fig.9: Gene Therapy [48]
1.6.10 Growth Factor Delivery: Growth factors are polypeptides released by numerous cells in a given time to stimulate cellular proliferation, differentiation, and migration. Regarding the key role of growth factors in the regulation of the wound healing process, controlled and sequential delivery to the wound sites is the topic of many current researches. Numerous growth factors such as EGF, VEGF, FGF, TGF, and PDGF have been studied in order to induce wound healing through angiogenesis, matrix deposition and re epithelialization. One of the main concerns in the delivery of growth factors is their short half-life, which instantly produces enzymatic degradation, thereby making their sustained release crucial in tissue engineering. Research findings have confirmed increased epithelialization, neovascularization, migration of keratinocytes, and fast healing of venous and diabetic foot ulcers after applying EGF on the wound site.[49]
On the other hand, clinical trials conducted on second-degree burn patients suggested that instant application of FGF on the wound surface can accelerate wound healing rates and formation of protective and strong granulated tissue. Interestingly, utilization of growth factors in combination with cells or natural materials for chronic and non-healing wound treatment has attracted extensive attention. For example, neovascularization, re-epithelialization, and wound closure have been documented in the results of studies using MSCs that secrete VEGF and platelet-rich plasma as potent sources of growth factors in full-thickness wounds.[50-51]
1.6.11 Scaffolds /biomaterial assisted wound healing: Scaffolds can be made of either natural or synthetic biomaterials, as well as a com bination of them in the form of hydrogels, electrospun fibers, films, etc. Biocompatibility, biodegradation, bioactivity, and cellular adhesion, are some of the properties of natural biomaterials. Collagen, gelatin, HA, chitosan, alginate, elastin, and silk fibroin are some of the natural polymers providing bioactive scaffolds that can create complex cellular interactions during healing . Among these natural materials, several studies have emphasized the significant effect of GAGs, and in particular HA, in wound healing. Presence of high water content in their molecular chain, along with the ability to act as a reservoir of growth factors, makes them ideal for the scope of tissue regeneration.[52-53]
From various forms of scaffolds, nanofibers and hydro gels are frequently utilized as a skin substitute with or without cells or bioactive therapeutics. Nanofibers can assist increasing cellular interactions by simulating a native ECM microenvironment, thereby improving adhesion and forming a porous structure. Nanofibrous wound dressings readily absorb exudates from the wound site while keeping them moistened as well as promoting oxygen diffusion through the injury. Moreover, owing to the high sur face to volume ratio, nanofibers can be easily modified for delivery of bioactive therapeutics. There are numerous methods for nanofiber synthesis such as phase separation, template synthesis, self-assembly, and electrospinning.[54]
Table 1: Various approaches used in wound healing
|
S.NO |
Approaches |
Material Used |
Advantages |
Reference |
|
1. |
Skin grafts |
|
|
Robinson, J. K., & Dillig, G. (2002). The advantages of delayed nasal full?thickness skin grafting after Mohs micrographic surgery. Dermatologic surgery, 28(9), 84851.[55] |
|
2. |
Wound dressing |
|
|
Zeng, Z., Zhu, M., Chen, L., Zhang, Y., Lu, T., Deng, Y., ... & Xiong, R. (2022). Design the molecule structures to achieve functional advantages of hydrogel wound dressings: Advances and strategies. Composites Part B: Engineering, 247, 110313.[56]
|
|
3. |
Vacuum assisted wound care |
|
|
Singh, D., Chopra, K., Sabino, J., & Brown, E. (2020). Practical things you should know about wound healing andvacuum-assisted closure management. Plastic andreconstructive surgery, 145(4),839e-854e. [57]
|
|
4. |
Stem cell therapy |
|
|
Kim, H. J., & Park, J. S. (2017). Usage of human mesenchymal stem cells in cell-based therapy: advantages and disadvantages. Development & reproduction, 21(1), 1 [58]
|
|
5. |
Cell therapy |
Culture media
|
|
Iancu, E. M., & Kandalaft, L. E. (2020). Challenges and advantages of cell therapy manufacturing under Good Manufacturing Practices within the hospital setting. Current Opinion in Biotechnology, 65, 233-241 [59] |
LITERATURE SURVEY
Gerard c, et.al (2000) studied and concluded that Traditional medicine, used widely by rural communities in most developing countries, serves as a mainstay for everyday health care for the majority of the world’s population.[79]
DISCUSSION
Wound healing is a complex biological process that involves the body's natural response to injury, aiming to restore the damaged tissue's structure and function. There are several approaches to wound healing, each with its advantages and considerations. The primary methods include natural healing, mechanical closure, and advanced therapies.
Wound healing typically progresses through several overlapping phases: Hemostasis, inflammation, proliferation, and Remodeling. During Hemostasis, blood vessels constrict to reduce bleeding, and platelets form a clot to seal the wound. In the inflammatory phase, immune cells like neutrophils and macrophages clear debris and defend against infection. The proliferation phase involves the formation of new tissue, including blood vessels and collagen deposition. Finally, Remodeling occurs as the scar tissue matures and contracts, improving the wound's strength and appearance over time.
Various factors can influence the wound healing process, such as age, nutrition, chronic illnesses like diabetes, and medications like steroids that impair immune function. Proper wound care, including cleaning, debridement (removal of dead tissue), and dressing selection, plays a crucial role in supporting optimal healing outcomes. Additionally, smoking and excessive alcohol consumption can delay wound healing by impairing blood flow and immune response.
Natural healing, also known as primary intention healing, occurs when the wound edges are closely approximated, allowing for direct healing without significant tissue loss. This approach is often seen in surgical incisions where the wound is sutured or stapled, promoting rapid healing and minimal scarring.
Mechanical closure involves techniques such as sutures, staples, or adhesive strips to bring the wound edges together. These methods are effective for larger wounds or those with irregular edges, facilitating the formation of a strong scar tissue matrix. However, they may require careful monitoring for infection and proper wound care to prevent complications.Advanced therapies encompass a range of techniques and technologies aimed at enhancing the healing process. This includes the use of growth factors, stem cells, bioengineered skin substitutes, and negative pressure wound therapy. These approaches are particularly beneficial for chronic wounds, diabetic ulcers, and severe burns, where traditional methods may be less effective .Despite advances in wound care, challenges such as chronic wounds, infections, and scarring remain significant concerns. Researchers continue to explore innovative technologies like 3D bioprinting of skin substitutes, nanomaterial-based dressings for targeted drug delivery, and gene therapy to enhance wound healing processes. These emerging approaches hold promise for improving outcomes and addressing the complexities of wound management in diverse clinical scenarios.
In summary, wound healing is a dynamic process influenced by various factors such as wound size, location, and patient's overall health. Understanding the different approaches to wound healing enables healthcare professionals to choose the most appropriate strategy for optimal outcomes and patient well-being.
CONCLUSION
In conclusion, wound healing is a sophisticated biological process that involves a sequence of events to repair damaged tissue and restore its normal function. The diverse approaches to wound healing reflect the complexity of this process and the need for tailored interventions based on the specific characteristics of each wound.Natural healing, characterized by primary intention healing, is optimal for wounds with clean, well-apposed edges, as it promotes rapid closure and minimal scarring. Mechanical closure methods, such as sutures, staples, and adhesive strips, are effective for wounds with irregular edges or significant tissue loss, providing mechanical support and facilitating healing.
Advanced therapies represent a frontier in wound care, leveraging cutting-edge technologies and treatments to address challenging wounds such as chronic ulcers, burns, and traumatic injuries. These therapies include the use of growth factors to stimulate tissue regeneration, bioengineered skin substitutes to promote wound closure, and negative pressure wound therapy to enhance healing in complex wounds.Moreover, factors such as patient age, comorbidities like diabetes or vascular disease, and lifestyle choices like smoking can significantly impact the wound healing process. Healthcare professionals must consider these factors when choosing an appropriate approach and implementing comprehensive wound management strategies.
Ultimately, the goal of wound healing approaches is not just to close the wound but to promote optimal healing outcomes, reduce the risk of complications such as infection or scarring, and improve patients' overall quality of life during the recovery process. Achieving these goals requires a multidisciplinary approach, integrating medical expertise, technological innovation,and patient-centered care to ensure the best possible outcomes for individuals undergoing wound healing.
REFERENCE
Rutika Chougule*, Ankita Chougale, Chaitali Patil, Sanika Patil, Study About Different Approaches in Biomedical for Treatment of Wound Healing, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 10, 169-188 https://doi.org/10.5281/zenodo.17243818
10.5281/zenodo.17243818
