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Wound healing in man: tensile strength of healing wounds in some patient groups.

The healing of test wounds was studied in 108 patients, in whom some impairment of wound healing was suspected. A 5 cm skin wound was performed in the forearm and the strength of the wound was tested after 5 days using the technique described by Sandblom and associates with two measurements in each wound. No differences in wound strength could be registered between the two wounds in each patient, between males and females nor in patients with malignant disease compared to other patients. Patients with low serum protein or serum albumin values had significantly weaker wounds than patients with normal protein values. Patients over 80 years of age had wounds somewhat weaker than those below 70, the difference having a statistical significance of 6%. The wound strength in patients was compared to values found elsewhere for wounds in rabbits, rats, and piglets. The pigs had much higher values than others, rabbits slightly stronger than and rats about equal to humans.

Age Factors

The biology of wound healing.

Wound healing is a complex biological process. A thorough knowledge of normal wound healing is of utmost importance for the clinicians who are involved in the care of patients with open wounds. It is imperative for every clinician who is involved in wound care to know the process which prevents, minimizes and eliminates those factors which adversely affect wound healing.

Bandages

Normal processes and restraints in wound healing.

Wound healing normally follows an uninterrupted course but, for the purposes of description, it can be considered in four phases -- hemostasis, acute inflammation, repair and consolidation. Arrest of healing may occur at any phase and lead to a number of clinical problems. Repair cannot begin until the phase of acute inflammation has begun to subside; this fact is of special importance in clinical surgery. Wound healing in gastrointestinal tract and abdominal incisions is emphasized because healing problems are common in these areas and failure to heal results in morbidity and a regrettable mortality.

Collagen

Spatiotemporal single-cell roadmap of human skin wound healing.

Wound healing is vital for human health, yet the details of cellular dynamics and coordination in human wound repair remain largely unexplored. To address this, we conducted single-cell multi-omics analyses on human skin wound tissues through inflammation, proliferation, and remodeling phases of wound repair from the same individuals, monitoring the cellular and molecular dynamics of human skin wound healing at an unprecedented spatiotemporal resolution. This singular roadmap reveals the cellular architecture of the wound margin and identifies FOSL1 as a critical driver of re-epithelialization. It shows that pro-inflammatory macrophages and fibroblasts sequentially support keratinocyte migration like a relay race across different healing stages. Comparison with single-cell data from venous and diabetic foot ulcers uncovers a link between failed keratinocyte migration and impaired inflammatory response in chronic wounds. Additionally, comparing human and mouse acute wound transcriptomes underscores the indispensable value of this roadmap in bridging basic research with clinical innovations.

Humans

Wound healing: a review. III. Nutritional factors affecting wound healing.

Wound healing proceeds more efficiently and quickly in well-nourished individuals who are in good general health at the time that they have to undergo surgery. Per contra, individuals who are malnourished and chronically ill heal less well and are in general at greater risk of complications during and after surgery. For the latter, elective surgery may be deferred until nutritional improvement is attained, but for emergency or urgent operations, institution of measures promoting good nutrition has to be concurrent with necessitous surgery and continued postoperatively. In this paper, the importance to wound healing of proteins, carbohydrates, fats, vitamins, and trace elements and minerals is reviewed.

Ascorbic Acid

[Transformation of monocytes into fibroblasts in wound healing (author's transl)].

Recent investigations of HELPAP and CREMER 1972 seem to confirm the supposition of COHNHEIM 1867 that monocytes of the peripheral blood are transformed into firbroblasts in healing wounds. The view of VIRCHOW 1871, MARCHAND 1901 and ASCHOFF 1924 that the fibroblasts in healing wounds are of local origin seems to be supported by the invesigation on parabiotic inbred rats of ROSS et al. 1970. We thought that irradiating the whole body of rabbits could be of value in resolving these apparent contradictions about the origin of fibroblasts in healing wounds.

Animals

Effects of early wound healing and wound treatment with zinc tape on intestinal absorption and distribution of zinc in rats.

In rats operated with large excisional skin wounds which were not treated with zinc tape, the serum zinc concentration was decreased at every observation time during the first post-operative day and the absorption of zinc from the intestine was increased. Slight decreases in the zinc concentration were seen in some tissues while liver zinc was very high. In rats with wounds treated with zinc tape, serum zinc was markedly increased at 6 hours, lower but above control levels at 7 and 12 hours and markedly increased again at 24 hours. The absorption of zinc from the intestine was low. Zinc concentration were elevated in most tissues sampled; they were high in testis and kidney and very high in liver. The results strongly indicate that the operative trauma and/or acute inflammatory conditions in the wounds in animals not treated with zinc tape initiate a movement of zinc from serum, some tissues and the content of the intestine to the liver. In the zinc tape treated group the increase in liver zinc was supplied mostly by the zinc tape. It is assumed that these large increases in zinc concentration in the liver are the result of the incorporation of zinc into certain zinc containing proteins which are produced in response to the inflammatory process in the wound. An increase was also found in the copper concentration in the liver of zinc tape treated animals and a decrease in the iron concentration in the liver of both groups of operated animals compared to controls.

Absorption

The influence of cortisol on wound healing of the skin and distant connective tissue response.

The effect of moderate dosage cortisol treatment on healing wounds and on the response in skin distant to the wounds was investigated. The stress-strain characteristics of a skin wound and intact skin specimens were examined. Also, skin thickness, water content and collagen content were measured. Cortisol treatment resulted in reduced extensibility and increased stiffness for ten day wounds, but unchanged failure energies; for 20 day wounds, failure energies were reduced, indicating reduced ability to withstand rupturing forces. Thus, the mechanical properties of healing wounds under moderate dosage, long term corticosteroid treatment were found to be slightly impaired. A systemic effect of wounding at day 10 resulted in decreased stiffness and increased collagen content of the skin distant to the wound.

Animals

Selective loss of blood group antigens during wound healing.

Frozen sections of healing wounds of the oral mucosa of 3 rhesus monkeys were examined by a double layer immunofluorescent technic for the presence of blood B-like antigens. Antigen activity was present in normal epithelium and in the epithelial outgrowth into the wounds but was absent from the outgrowth following treatment with lipid solvents. This finding suggests that glycoprotein but not glycolipid associated antigen is lost from the surface of epithelial cells during wound healing, a pattern of selective loss which may reflect a difference between regenerative and neoplastic lesions.

Animals

Wound healing: a review. II. Environmental factors affecting wound healing.

A variety of factors, both intrinsic and extrinsic, may influence the healing of wounds. Some of these influences are environmental in nature and subject to advantageous manipulation by the practitioner. In this article, the role of humidity, temperature, infection and oxygen tension on the process of wound healing will be discussed.

Bacterial Infections

Effect of suture materials on healing wounds of the stomach and colon.

Wound healing in the stomach and colon of mongrel dogs was studied using physical, histologic and chemical techniques to evaluate effects of various suture materials on the healing pattern and to compare visceral wounds with skin wounds. The general pattern of healing for stomach and colon wounds is the same in rats, rabbits and dogs. However, the extent of healing, the percentage of strength of normal tissue attained by the wound, is less in the dog than in the rat or rabbit. Prolene and plain and chromic catgut produce the least and silk produces the greatest cellular reaction in the stomach and colon. We believe the effect of absorbable sutures on strength of stomach and colon wounds, while statistically significant, is not of any great clinical significance except perhaps in severely debilitated patients. A trial of Prolene sutures for anastomotic closure would seem indicated. The healing of stomach and colon wounds differs from the pattern observed for skin wounds. Breaking strength increases rapidly for 14 to 21 days postwounding and then does not change significantly. The wounds are metabolically more active than skin wounds since the rate of collagen synthesis is markedly elevated even after 120 days and the rate of noncollagenous protein synthesis is twice as great in the wound as it is in normal tissue. Colon and stomach wounds closed with absorbable sutures are weaker at 14 through 28 days than similar wounds closed with nonabsorbable sutures. Yet, when strength of wound is expressed as a percentage of strength of unwounded tissue, there is no difference between wounds blosed with absorbable or nonabsorbable sutures. Thus, it would appear that there is a general diminution of the strength of normal stomach and colon wall up to 6 centimeters from wounds which have been closed with absorbable sutures.

Animals

Biologic determinants of tumor growth in healing wounds.

The morphologic characteristics of a scar may render it an "immunologically privileged site" providing fertile ground for tumor occurrence and growth. We sought to extend this concept and to determine the effect of different stages of wound healing on tumor occurrence. Syngeneic strain-2 guinea pigs and a methylcholanthrene-induced liposarcoma (MCA-2) were used. Incisional flank wounds were created at appropriate intervals such that at the time of tumor inoculation each group of animals had a sequentially aged wound which was a) acute, b) three weeks old, c) nine weeks old, d) 11 weeks old, e) created one week after tumor injection, or f) no wound. Wounds which were three, nine, or 11 weeks old consistently caused a significant increase in tumor growth rate following inoculation of a single cell tumor suspension (<.001). The delayed wounds, or those created following after tumor injection, and the acute wounds did not promote increased tumor growth. This study demonstrates that the ability of a wound to amplify or retard tumor growth may vary with its age. As a postulate we suggest that the relative paucity of lymphatic regeneration within scar tissue may render it an "immunologically privileged site" such that early recognition and destruction of tumor cells within the scar may be delayed long enough for the tumor to grow to a "critical size." Subsequent to this regardless of the host's immunocompetence the tumor can no longer be destroyed by an immune mechanism. The general lack of progressive growth of tumor cells placed in acute wounds suggests that they were not protected from immunocompetent cells and were destroyed by the ongoing inflammatory response to injury. Therefore, different biologic characteristics of a surgical scar are important in potentiating or retarding tumor growth. Variations in such factors may account for the local recurrence of cancer in operative wounds.

Animals

Role of serum nonsuppressible insulin-like activity (NSILA) in wound healing. I. Influence of thyroparathyroidectomy on serum NSILA and wound healing in the rat.

Serum contains a 90,000 molecular weight glycoprotein that exhibits insulin-like activity on adipocytes, skeletal muscle, and fibroblasts in tissue culture; however, this protein is physicochemically and immunochemically distinct from insulin and presently is termed "nonsuppressible insulin-like activity ("nsilA)." This study was designed to assess the response of serum NSILA to thyroparathyroidectomy (TPTHX) and to associate this response with tissue repair processes in the injured rat. It was postulated that NSILA modulates the fibroblastic response in wound healing. TPTHX decreased NSILA to 40 percent of control levels (p less than 0.001); 90 male animals subsequently were wounded by either a 10 percent third-degree burn or skin excision. Following injury, NSILA significantly increased in both control and TPTHX groups, but this acute-phase response was attenuated in TPTHX animals. Light microscopy of granulation tissue demonstrated a diminution in the fibroblastic response in TPTHX animals. Hydroxyproline analysis of granulation tissue revealed a significant decrease (p less than 0.025) in collagen content in TPTHX animals with low NSILA levels. The results suggest that serum NSILA levels are controlled, in part, by thyroid hormone and that NSILA may modulate the fibroblastic response of connective tissue repair processes.

Animals

Integrative Network Analysis of Bioactive Compounds from Punica granatum L. Peel: Multi-Target Mechanisms in Wound Healing.

BACKGROUND: Wound-healing agents often have limited efficacy and require prolonged recovery times, prompting growing interest in developing herbal-based formulations. Among these, Punica granatum L. has attracted considerable attention because of its high polyphenolic content. Despite its widespread use, the precise pharmacological targets underlying its wound-healing effects remain poorly understood and require systematic investigation. OBJECTIVES: This study aimed to elucidate the underlying pharmacological mechanisms of the topical wound-healing properties of P. granatum L. using a network pharmacology approach. METHODS: Bioactive compounds of P. granatum L. and their potential target genes were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Similarity Ensemble Approach (SEA), and SwissTargetPrediction databases. Wound healing-related genes were retrieved from the GeneCards database. Genes intersecting P. granatum L. targets and wound healing-associated genes were subjected to functional enrichment analyses, including protein-protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The PPI network was further analyzed using Cytoscape, and the phytoconstituent-target interaction network was visualized using Gephi. These findings were validated using molecular docking. RESULTS: A total of 40 intersecting genes were identified as potential P. granatum L. targets involved in wound healing. Among these, EGFR, PTPN11, HRAS, IGF1R, and ESR1 were identified as key hub genes. Functional enrichment analysis indicated that the most significantly enriched signaling pathways included the MAPK, PI3K-Akt, EGFR tyrosine kinase inhibitor resistance, focal adhesion, and FoxO signaling pathways. Molecular docking analysis confirmed favorable binding of quercetin and ellagic acid to the hub targets EGFR, IGF1R, and ESR1. CONCLUSIONS: These findings elucidate the pharmacological pathways underlying P. granatum-mediated wound healing and suggest that P. granatum L. acts as a multi-target modulator in the wound-healing process.

Focal Adhesion

The role of growth factor in wound healing.

A pig wound healing model was developed to study the morphological processes involved in incisional and excisional wound healing, the immunohistochemical localization of TGF-alpha in wound healing, and the latter's relevance. In incisional wounds, a few layers of epidermis were regenerated after only 32 hours. In contrast, several layers of epidermis were regenerated on day 7 in excisional wounds. In general, the incisional wound model is useful for evaluating tensile strength, while the excisional wound model is suitable for evaluating epidermal regeneration. Immunohistochemical study showed that keratinocytes migrating from wound edges expressed TGF-alpha very faintly, while TGF-alpha was present prominently in the upper several layers of the epidermis adjacent to the wound, which resembled normal epidermis and showed no changes during the wound healing process.

Animals

Wound healing. Comparison of healing rates of burn wounds and of excisional wounds.

The process of healing of skin excisions and skin burns of equal sizes has been compared in rabbits. Excisions heal definitely quicker than burns, despite the fact that the part of the skin exposed to the burning agent does not undergo necrosis. Small excisional wounds heal more rapidly than larger ones but the healing rate of burn wounds in our series was independent of their size. Secondary excision of the burned tissue accelerates the healing process. Thus the healing time of burn wounds seems to depend more on clearing the wounds of the necrotic tissue than on the mere repair of the skin loss.

Animals

Effects and prevention of frostbite in wound healing.

Observations on wounds sustained at subfreezing temperatures in husky dogs and in man suggested that exposed wet tissues readily become frozen. Frostbite of wounds caused tissue necrosis, wound sepsis and delayed healing, but immediate wound suture protected against this sequence. To explore the effect of wound closure on healing frostbitten tissue, healing of paired dorsal wounds was studied in 20 rats. In each animal one wound was sutured and the other was left open. In 10 animals both wounds were frozen with Dry Ice. All sutured wounds healed primarily. Most of the control open wounds had healed at 15 days, but in the frozen wounds healing was delayed and infection ensued. It is suggested that at temperatures much below freezing the immediate treatment of a wound should include prevention of frostbite by wound closure.

Animals