INTRODUCTION:

A skin wound occurs when the integrity of the epidermal layer is compromised¹. A wound is characterized as any injury to tissue that compromises its anatomical integrity and results in a loss of function. The capacity of an organism to heal or regenerate its tissues provides a significant advantage for survival². The process by which skin wounds heal is sometimes referred to as "wound healing." This process can take years to finish completely and starts as soon as the epidermal layer is damaged. The process of wound healing is dynamic and involves highly specialized humoral, molecular, and cellular systems² The four overlapping stages of this process are remodeling, proliferation, inflammation, and hemostasis.³ Any interference with these mechanisms may result in aberrant wound healing.⁴

Classification of Wounf Healing:

Wounds can generally be divided into two categories: acute and chronic, depending on the duration since the initial injury and the advancement through the typical stages of wound healing.

Acute Wounds:

The initial stage, hemostasis, occurs within minutes to hours following the injury. This is succeeded by the inflammatory phase, which generally persists for 1 to 3 days. The third stage of wound healing is proliferation, lasting from several days to a month. Finally, the fourth phase, remodeling or scar formation, usually extends for 12 months but may continue for as long as 2 years post-injury. Acute wounds can be further categorized into open or closed types^5,6.

Open wounds:

· A clean, sharp-edged item, such a knife, razor, or glass splinter, can cause incisions or incised wounds

· Abrasions, also known as grazes, are superficial injuries characterized by the removal of the outermost layer of skin, referred to as the epidermis. These types of wounds frequently occur as a result of sliding falls onto abrasive surfaces like asphalt, tree bark, or concrete.

· Puncture wounds are injuries that occur when an object penetrates the skin, which can include items such as a splinter, nail, knife, or sharp tooth.

· Penetration wounds – resulting from an object, like a knife, piercing through the skin and exiting from it⁷.

Closed wounds:

· Hematomas, also known as blood tumors, occur due to the injury of a blood vessel, which subsequently leads to the accumulation of blood beneath the skin.

· Hematomas resulting from an external traumatic source are referred to as contusions, which are more commonly known as bruises.

· Crush injury – resulting from a significant or excessive force exerted over an extended duration⁸.

Chronic wounds:

Typically, these wounds arise from an underlying medica It is crucial to understand that any acute wound can potentially develop into a chronic wound if any of the standard stages of wound healing are disrupted. Chronic wounds typically arise from an interruption in the inflammatory phase of the healing process; however mistakes in any phase can lead to the formation of a chronic wound.^l condition, such as diabetes mellitus or arterial/venous insufficiency. The precise time frame that separates an acute wound from a chronic wound is unclear, although most clinicians concur that wounds that have not healed for more than three months are classified as chronic wounds.^9,10

Common causes of chronic wounds:

Diabetes mellitus - Diabetes-related impairment of wound healing is complex. Diabetic wound formation and spread have been linked to a number of variables, including hyperglycemia, neuropathy, microvascular problems, compromised immunological and inflammatory responses, and psychosocial issues. Up to 25% of people with diabetes mellitus are predicted to get non-healing wounds at some point in their lives¹¹.

Venous/Arterial insufficiency - Chronic wounds can result from either impaired venous or arterial blood outflow or influx, which can hinder wound healing. Similar to diabetes, chronic lower extremity wounds are the most typical outcome of venous/arterial insufficiency. Conversely, peripheral artery disease usually affects the most distal extremities (fingers, toes) and results in wounds from inadequate blood supply ^12,13,14,15.

Immunologic disease: Since the immune system is essential to the inflammatory process, any immune system disorder may hinder the inflammatory stage of wound healing and result in a chronic wound¹⁶.

Pressure ulcer: Commonly referred to as decubitus ulcers or bedsores, this type of wound arises from sustained pressure on the skin over an extended duration. Although most individuals possess intact sensory and motor functions that facilitate regular positional changes to avert the development of such ulcers, elderly individuals are especially vulnerable to this form of chronic injury due to diminished neurosensory responses ¹⁷.

Stages of wound healing (mechanism):

Inflammatory stage: In a vascular inflammatory response, the damaged blood vessels undergo contraction, and the blood that has leaked coagulates, which aids in preserving its integrity. The process of coagulation involves the aggregation of thrombocytes and platelets within a fibrin network, depending on the action of specific factors that facilitate the activation and aggregation of these cells¹⁸. The cellular response during the inflammatory phase is marked by the arrival of leukocytes to the wound site. This response occurs rapidly and aligns with the primary indicators of inflammation, which are manifested through edema and erythema at the site of injury. Typically, the cellular response is initiated within the first 24hours and may persist for up to two days.

A swift activation of immune cells within the tissue can also take place, as seen with mast cells, gamma-delta T cells, and Langerhans cells, which release chemokines and cytokines. Inflammatory cells are crucial in the process of wound healing, aiding in the release of lysosomal enzymes and reactive oxygen species, while also assisting in the removal of various cellular debris¹⁹.

Fig: Stages of wound healing²⁰

Proliferative Stage:

The objective of the proliferative phase is to reduce the area of damaged tissue through contraction and fibroplasia, thereby creating a functional epithelial barrier that stimulates keratinocytes. This phase is crucial for the actual closure of the lesion, which encompasses angiogenesis, fibroplasia, and reepithelialization. These processes initiate in the lesion's microenvironment within the first 48hours and may continue until the 14th day following the onset of the lesion²¹.

Vascular remodeling induces alterations in blood flow. Angiogenesis is a systematic process that encompasses endothelial cell proliferation, the rupture and reorganization of the basal membrane, migration and assembly into tubular formations, as well as the recruitment of perivascular cells. For an extended period, angiogenesis has been recognized as crucial for various physiological and pathological states, including embryogenesis, tumor development, and metastasis²².

Through extensive cytoplasmic extensions that extend and encircle the endothelial tube, the pericyte establishes focal contact with the endothelium via specialized junction. Furthermore, this type of cell influences the stability of blood vessels by depositing matrix components and/or by releasing and activating signals that encourage the differentiation or compliance of endothelial cells^23,24,25.

Remodelling Phase:

The remodelling phase, which represents the concluding stage of wound healing, is scrucial for the formation of new epithelium and the finalization of scar tissue. The synthesis of the extracellular matrix during both the proliferative and remodelling phases begins simultaneously with the development of granulation tissue. This phase can extend for a duration of 1 to 2 years, and in some cases, it may persist for an even longer timeframe^26,27.

Collagen fibers can recover about 80% of their initial strength when compared to unwounded tissue. The ultimate strength achieved is influenced by the location of the repair and the time taken for healing; however, the original strength of the tissue cannot be fully restored ^28,29.

The underlying connective tissue reduces in size, drawing the wound edges nearer, due to the interactions of fibroblasts with the extracellular matrix. Several factors regulate this process, with PDGF, TGF-β, and FGF being the most critical^30,31.

Factor Affecting on Wound

Local factor	Systemic factor
Oxygenation	Age
Infection	Gender
Foreign body	Sex hormones
Venous sufficiency.	Ischemia, Obesity

Oxygenation:

Oxygen plays a vital role in cellular metabolism, particularly in the production of energy through ATP, and is essential for almost all processes involved in wound healing.

Due to the disruption of vascular flow and the elevated oxygen demand from metabolically active cells, the microenvironment of an early wound experiences a depletion of oxygen, resulting in a hypoxic condition. Various systemic factors, such as advancing age and diabetes, can lead to compromised vascular circulation, thereby establishing conditions for inadequate tissue oxygenation. In terms of the healing process, this combination of poor blood flow results in a hypoxic wound. Chronic wounds are particularly characterized by hypoxia; tissue oxygen levels have been recorded transcutaneously in chronic wounds ranging from 5 to 20 mm Hg, compared to control tissue values which range from 30 to 50mm Hg.

Infections:

When the skin is damaged, micro-organisms that are typically confined to the surface of the skin gain entry to the deeper tissues. The level of infection and the replication status of these micro-organisms ditact how the wound is categorized, which may include contamination, colonization, local infection/critical colonization, and/or spreading invasive infection. Contamination refers to the existence of non-replicating organisms on a wound, whereas colonization is characterized by the presence of replicating microorganisms on the wound without causing tissue damage. Local infection or critical colonization represents an intermediate phase, marked by microorganism replication and the onset of local tissue responses. Invasive infection is defined as the presence of replicating organisms within a wound, leading to subsequent injury to the host.

Systemic factors affecting wound healing:

DIABETES:

· Ischemia can lead to prolonged inflammation, which increases the levels of oxygen radicals, leading to further tissue injury.

· In chronic diabetic wounds, elevated levels of matrix metalloproteases can be observed, sometimes reaching 50-100 times higher than those found in acute wounds. This increase leads to tissue destruction and hinders the normal repair processes from occurring.³²

Deficiency States/Malnutrition:

Wounds necessitate various micro and macronutrients for effective healing. In terms of macronutrients, proteins serve as the essential building blocks of our tissues, underscoring the significance of a sufficient intake of protein and amino acid-rich nutrition to facilitate proper wound healing. Amino acids like arginine and glutamine are crucial to the overall process of wound healing.

Arginine enhances immune function, aids in collagen deposition, and contributes to neovascularization. Additionally, arginine supplementation positively influences wound healing.

Carbohydrates, mainly glucose, serve as the main energy source for cells as they are metabolized to produce adenosine triphosphate (ATP). Polyunsaturated fatty acids, including omega-3 and omega-6 fatty acids, which are both essential, can improve wound healing by positively influencing the host's immune function.

Several micronutrients play a particularly important role in wound healing. These include ascorbic acid or vitamin C, vitamin A, vitamin E, as well as magnesium, zinc, and iron.³²

Medication:

Anticoagulants

· Angiogenesis inhibitors

· Antineoplastic drugs

· Cyclosporine A

· Cholchicine

· Penicillamine

· Zinc sulfate (high doses)

· Beta amino proprionitrile

OBESITY:

Abdominal obesity is correlated with oxidative stress, and is associated with deficiency of adiponectin. Adiponectin-deficient state leads to impaired perfusion and reepithelialization of the wound. Pressure ulcers are more common in obese patients through pressure-related ischemia as well as decreased mobility.

Stress:

Stress significantly affects both human health and social behaviour Various illnesses—including cardiovascular disease, cancer, impaired wound healing, and diabetes—are linked to stress. A multitude of studies has verified that the disruption of neuroendocrine immune balance caused by stress has serious implications for health. The pathophysiology of stress leads to the dysregulation of the immune system, primarily mediated by the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic-adrenal medullary axes, or the sympathetic nervous system. Research involving both humans and animals has shown that psychological stress significantly hinders the process of wound healing. Caregivers of individuals with Alzheimer’s disease, as well as students experiencing academic pressure during exams, exhibited delays in wound healing. Stress increases the levels of glucocorticoids (GCs) and decreases the concentrations of the proinflammatory cytokines IL-1β, IL-6, and TNF-α at the site of the wound. Stress further diminishes the expression of IL-1α and IL-8 at wound locations—both of which are chemoattractants essential for the initial inflammatory phase of the wound healing process.

Diagnosis of wound:

Translational Relevance:

Numerous innovative technologies have been developed in recent years for the diagnosis of infected wounds. Alongside physiological assays, conventional imaging methods like radiography and magnetic resonance imaging (MRI), in addition to emerging hybrid imaging techniques such as single-photon emission computed tomography (SPECT)/computed tomography (CT) and positron emission tomography (PET)/MRI, are being employed as diagnostic tools for wound infections.^33,34

Clinical Relevance:

Wound infections pose challenges not only for patients but also for healthcare systems globally that offer care to these individuals. Although current tools and methods have achieved a fair degree of success in managing wound infections, new diagnostic instruments and technologies present significant promise in the clinical management of wounds. These techniques have considerable potential to furnish supplementary information regarding the diagnosis of wound infections and to guide subsequent treatment strategies. Understanding these diagnostics can enhance the precision of clinical validation, considering the vast variety of wound types, anatomical locations, and tissues involved.³⁵

Laboratory Markers:

Alongside the techniques for wound culture, laboratory markers can be assessed to assist in diagnosing wound infections. These markers consist of C-reactive protein (CRP), procalcitonin (PCT), presepsin, microbial DNA, and bacterial protease activity (BPA). In reaction to inflammation and infection, C-reactive protein (CRP), a peptide synthesized in the liver, is activated by cytokines, chiefly interleukin-6, and utilized in complement binding and phagocytosis by macrophages.³⁶

Treatment of wound healing:

· Cleaning to remove dirt and debris from a fresh wound. This is done very gently and often in the shower.

· Tetanus vaccination may be recommended for tetanus-prone wounds.

· Exploring a deep wound surgically may be necessary. Local anaesthetic will be given before the examination.

· Removing dead skin surgically. Local anaesthetic will be given.

· Closing large wounds with stitches or staples.

· Dressing the wound. The dressing chosen by your doctor depends on the type and severity of the wound. In most cases of chronic wounds, the doctor will recommend a moist dressing.

· Using aids such as support stockings. Use these aids as directed by your doctor.

· Treating other medical conditions, such as anaemia, that may prevent your wound healing.

· Prescribing specific antibiotics for wounds caused by Bairnsdale or Buruli ulcers. Skin grafts may also be needed³⁷.

REFERENCES:

1. Heng MC. Wound healing in adult skin: aiming for perfect regeneration. Int J Dermatol. 2011 Sep; 50(9): 1058-66.

2. Reinke JM, Sorg H. Wound repair and regeneration. Eur Surg Res. 2012; 49(1):35-43.

3. Sim SL, Kumari S, Kaur S, Khosrotehrani K. Macrophages in Skin Wounds: Functions and Therapeutic Potential. Biomolecules. 2022 Nov 08;12(11)

4. Cullen B, Smith R, McCulloch E, Silcock D, Morrison L. Mechanism of action of PROMOGRAN, a protease modulating matrix, for the treatment of diabetic foot ulcers. Wound Repair Regen. 2002 Jan-Feb;10(1):16-25.

5. Wallace HA, Basehore BM, Zito PM (2023). "Wound Healing Phases". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 29262065. Retrieved 19 January 2024.

6. Raziyeva K, Kim Y, Zharkinbekov Z, Kassymbek K, Jimi S, Saparov A. Immunology of Acute and Chronic Wound Healing. Biomolecules. 2021; 11(5): 700. doi:10.3390/biom11050700. Cuts and puncture wounds. MedlinePlus Medical Encyclopedia. U.S. National Library of Medicine. Retrieved 8 November 2023

7. Ibrahim DA, Swenson A, Sassoon A, Fernando ND. Classifications In Brief: The Tscherne Classification of Soft Tissue Injury. Clinical Orthopaedics and Related Research. 2017; 475(2): 560–564. doi:10.1007/s11999-016-4980-3.

8. Nagle SM, Stevens KA, Wilbraham SC (2023). "Wound Assessment". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 29489199. Retrieved 12 January 2024.

9. Star A. Differentiating Lower Extremity Wounds: Arterial, Venous, Neurotrophic. Seminars in Interventional Radiology. 2018; 35(5): 399–405. doi:10.1055/s-0038-1676362.

10. Burgess JL, Wyant WA, Abdo Abujamra B, Kirsner RS, Jozic I. Diabetic Wound-Healing Science. Medicina. 2021; 57(10): 1072. doi:10.3390/medicina57101072. PMC 8539411. PMID 34684109.

11. Star A. Differentiating Lower Extremity Wounds: Arterial, Venous, Neurotrophic. Seminars in Interventional Radiology. 2018; 35(5): 399–405. doi:10.1055/s-0038-1676362. PMC 6363550. PMID 30728656.

12. Burgess JL, Wyant WA, Abdo Abujamra B, Kirsner RS, Jozic I. Diabetic Wound-Healing Science. Medicina. 2021; 57(10): 1072. doi:10.3390/medicina57101072.

13. Robles-Tenorio A, Lev-Tov H, Ocampo-Candiani J (2023). "Venous Leg Ulcer". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 33620871.

14. ReZemaitis MR, Boll JM, Dreyer MA (2023). "Peripheral Arterial Disease". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 28613496. Retrieved 19 January 2024.trieved 19 January 2024.

15. Avishai E, Yeghiazaryan K, Golubnitschaja O. Impaired wound healing: facts and hypotheses for multi-professional considerations in predictive, preventive and personalised medicine. The EPMA Journal. 2017; 8(1): 23–33. doi:10.1007/s13167-017-0081-y.

16. Zaidi SR, Sharma S (2023). Pressure Ulcer. StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 31971747. Retrieved 19 January 2024.

17. Shaw TJ, Martin P. Wound repair at a glance. J Cell Sci. 2009; 122: 3209-13.

18. Medrado AR, Pugliese LS, Reis SR, Andrade ZA. Influence of low-level laser therapy on wound healing and its biological action upon myofibroblasts. Lasers Surg Med. 2003; 32: 239-44.

19. https://share.google/FfrbHdUpJeYFlv0kz.

20. Li J, Chen J, Kirsner R. Pathophisiology of acute wound healing. Clin Dermatol. 2007; 25: 9-18

21. Rosen BP. Biocemistry of arsenic detoxification. FEBS Lett. 2002; 529: 86-92.

22. Armulik A, Genové G, Betsholtz C. Pericytes: Developmental, Physiological and Pathological Perspectives, Problems and Promises. Dev Cell. 2011; 21: 193-215.

23. Xian X, Håkansson J, Ståhlberg A, Lindblom P, Betsholtz C, Gerhardt H, et al. Pericytes limit tumor cell metastasis. J Clin Invest. 2006; 116: 642-51

24. Takakura N. Role of hematopoietic lineage cells as accessory components in blood vessel formation. Cancer Sci. 2006; 97: 568-74.

25. Witte MB, Barbul A: General principles of wound healing. Surg Clin North Am 1997; 77: 509– 528

26. Ramasastry SS: Acute wounds. Clin Plast Surg. 2005; 32: 195– 208.

27. RobsonMC, Steed DL, Franz MG: Wound healing: biologic features andapproaches to maximizehealing trajectories. Curr Probl Surg. 2001; 38: 72–140.

28. Sieggreen MY: Healing of physical wounds. Nurs Clin North Am. 1987; 22: 439– 447.42– 48.

29. Clark RA: Regulation of fibroplasia in cutaneous wound repair. Am J Med Sci. 1993; 306: 42– 48.

30. Pierce GF, Vande Berg J, Rudolph R, et al: Platelet-derived growth factor-BB and transforming growth factor beta 1 selectively modulate glycosaminoglycans, collagen, and myofibroblasts in excisional wounds. Am J Pathol. 1991; 138: 629– 646.

31. Avishai E et al. Imapired wound healing: facts and hypothesis for multi-professional considerations in predictive, preventive and personalized medicine, EPMA Journal. 2017; 8: 23-33.

32. Van Asten SA, Jupiter DC, Mithani M, La Fontaine J, Davis KE, Lavery LA. Erythrocyte sedimentation rate and C-reactive protein to monitor treatment outcomes in diabetic foot osteomyelitis. Int Wound J. 2017; 14: 142–148.

33. Spoto S, Valeriani E, Caputo D, et al. The role of procalcitonin in the diagnosis of bacterial infection after major abdominal surgery: advantage from daily measurement. Medicine (Baltimore). 2018; 97: e9496.

34. Järbrink K, Ni G, Sönnergren H, et al. The humanistic and economic burden of chronic wounds: a protocol for a systematic review. Syst Rev. 2017; 6:15.

35. Xia D, Samols D. Transgenic mice expressing rabbit C-reactive protein are resistant to endotoxemia. Proc Natl Acad Sci USA. 1997; 94: 2575–2580

36. Menke NB, Ward KR, Witten TM, Bonchev DG, Diegelmann RF (2007). Impaired wound healing. Clin Dermatol. 25:19-25.

Received on 27.03.2026 Revised on 16.04.2026

Accepted on 04.05.2026 Published on 10.07.2026

Available online from July 14, 2026

Res.J. Pharmacology and Pharmacodynamics.2026;18(3):277-281.

DOI: 10.52711/2321-5836.2026.00037

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.