alginates, alternative, dextran, gelatin, honey, hydrogels, natural, phytochemicals, polymers, polyurethane, wound care



  1. Sathe, Pushkar Satish MPharm
  2. Prabhu, Divyashree V. MPharm
  3. Ravikumar, Padmini PhD
  4. Bolton, Laura L. PhD


GENERAL PURPOSE: To present a scoping review of preclinical and clinical trial evidence supporting the efficacy and/or safety of major alternative wound care agents to summarize their effects on validated elements of wound bed preparation and wound management paradigms.


TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care.


LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will:


1. Differentiate the effectiveness of the topical wound care agents included in this review.


2. Compare the preventive efficacy of intravenous agents administered to trauma and surgical patients.


3. Select the effectiveness of products in this review that are left in place after surgical procedures.


4. Identify an oral agent that can be helpful in mitigating the effects of COVID-19.


ABSTRACT: Effective wound healing is achieved by well-timed host, cell, and environment interactions involving hemostasis, inflammation, formation of repaired dermal structures, and epithelialization, followed by months to years of scar remodeling. Globally, various natural or synthetic agents or dressings are used to optimize wound environments, prolong drug release, aid in fluid absorption, provide favorable healing environments, and act as a mechanical barrier against wound trauma. In this scoping review of evidence from the PubMed and databases, authors examined clinical study evidence supporting the efficacy and safety of selected phytochemicals, vehicles, polymers, and animal products considered "naturally derived" or "alternative" wound interventions to provide a summary of preclinical evidence. Agents with the most clinical evidence were honey, alginates, polyurethane, gelatin, and dextran. Practice implications are described in the context of the TIMERS clinical paradigm.


Article Content


The World Health Organization has estimated that 312.9 million surgical procedures were performed in 20161 and that millions of children and adults suffer the physical and emotional trauma of burns, conferring more than $300 million of economic burden on patients and systems.2 In 2014, in the US alone, 8.2 million Medicare beneficiaries had at least one chronic or acute wound or related infection (an estimated cost of US$28.6 to US$96.8 billion).3 Although the true clinical, economic, and patient-centered burden of wounds remains to be clarified, wound care is clearly a global concern affecting hundreds of millions of people annually.


Wounds may be classified based on their locations, depth, nature or cause of injury,4,5 and whether they are acute or chronic.6 Acute wound healing requires good circulation, immune function, and a moist environment free of dead tissue or foreign matter supporting function of the many cells and molecules that participate in repair.7-9 Chronic wounds are often resistant to treatment and need prolonged time to heal. Repair can be hindered by environmental factors such as trauma, desiccation, and infection; or host factors such as immune deficiency, compromised circulation, or respiratory function, which delay the normal progression through these healing phases.6


The rich global heritage of naturally derived wound healing products, sometimes loosely described as "alternative" agents, have received increased attention recently, and many researchers have explored their safety and efficacy in wound management.7-9 Preclinical evidence presented in the Table suggests many ways that various agents obtained from plant or animal sources as well as certain smart excipients may affect wound environments.10-21

Table PRECLINICAL EV... - Click to enlarge in new windowTable

Supporting evidence for translating theory into practice for alternative wound care agents has been described as "promising"22 but remains to be summarized in the context of clinical practice for wound bed preparation23,24 and management paradigms.25,26



The authors conducted a scoping review of preclinical and clinical trial evidence supporting the efficacy and/or safety of major alternative wound care agents to summarize their effects on validated elements of wound bed preparation and wound management paradigms.



The PubMed reference database was searched from January 1, 1970, through November 20, 2020, for original and derivative clinical trial references addressing the MeSH (Medical Subject Headings) terms for "clinical trial" combined with those for each of the agents listed in the Table. Randomized controlled trials (RCTs) or nonrandomized clinical trials were included if they reported a significant improvement (P < .05) in one or more measured and valid wound outcomes.27 Case studies were included to support wound safety, but in vivo and in vitro studies were excluded, as were those unrelated to cutaneous wound care or the alternative agents in question. Further, studies combining an alternative agent with other agents, preventing evaluation of its specific effects, were excluded from analysis.


All authors evaluated the clinical literature search results and a single investigator extracted from qualifying clinical studies the first author's last name, year of publication, type of clinical study (randomized, nonrandomized, or case series), number of patients studied, and wound etiology. Data were used to populate a spreadsheet, which calculated the number of studies supporting each agent. The usefulness of each agent was then described based on its reported outcomes related to elements of the TIMERS (Tissue management, reducing Inflammation and Infection, Moisture balance, Edge and Epithelial advancement, Regeneration and Repair, or Social issues) wound management mnemonic.



Of 1,380 references screened, 281 abstracts or full-text articles were reviewed, and 274 studies on 28,315 patients were included in the analysis (Figure 1). Agents with more than 10 RCTs supporting clinical wound outcomes (Figure 2) were honey, alginate gels or fiber dressings, polyurethane gel or adhesive dressing, aloe vera gel, or dextran powder. Results are discussed below indicating each agent's potential roles in wound management using the TIMERS paradigm or meeting other aspects of patient or wound clinical needs.

Figure 1 - Click to enlarge in new windowFigure 1.
Figure 2 - Click to enlarge in new windowFigure 2.

Two case series involving 24 patients supported the safety of agar hydrogel (TIMERS component: E) in epithelializing skin graft donor sites (SGDSs).


Thirty-two clinical trials involving 2,147 patients included alginate dressings (TIMERS components: I, M, E). These dressings contain highly absorbent calcium alginate or calcium sodium alginate fibers or yarns that support hemostasis or form a gel when in contact with a moist wound surface; accordingly, they can be lifted off or washed off at dressing removal. They improved healing or reduced infection rates of SGDSs compared with gauze dressings, with similar wound healing outcomes to hydrofiber, film, or silicone dressings, which all healed SGSD at least 7 days more slowly than SGDSs dressed with a hydrocolloid dressing.28 The benefits of alginate dressings were less clear for venous leg ulcers,29 diabetic foot ulcers,30 or pressure injuries,31 because alginate dressings were often used in combination with other dressings or agents. Healing and pain improvement were similar for chronic or acute wounds dressed with an alginate or a silver dressing.32 In participants with chronic wounds and high bacterial burdens, topical silver alginate powder reduced wound area and signs of infection over 4 weeks compared with a foam dressing.33 Studies of such combined interventions or studies where "standard care" included alginates with other dressings were not included in Figure 2 because it was not possible to discern the specific effects of the alginate component of the dressing.


This review included 18 clinical trials on aloe vera use for 1,113 patients (TIMERS components: I, E). Systematic reviews reported improved healing of patients with burns and burn wound infection managed with aloe vera, with effects comparable with those of topical antibiotics or antiseptics.34 Improved healing was reported for pressure injuries cleansed with a spray containing physiologic saline, aloe vera, and decyl glucoside compared with isotonic saline, but it was not clear that aloe vera caused the healing effect.35


Calendula officinalis (Marigold) or C flos extract was examined by 9 clinical studies involving 1,086 patients (TIMERS components: I, E). Marigold was typically delivered as a 3% ointment or hydroglycolic spray, with varying effects.36 Reduced pain and improved healing were reported for gynecologic surgical wounds, venous leg ulcers, and diaper dermatitis, but not diabetic leg ulcers or partial-thickness burns compared with standard of care. The extract improved radiation dermatitis symptoms compared with trolamine, with similar healing benefits to topical aqueous gel.36


Centella asiatica was included in 9 clinical studies on at least 426 patients (TIMERS components: I, E) with chronic or surgical wounds and second-degree burns; this agent reportedly improved healing, nerve injury, and scar tissue.37


The search for chitin or chitosan returned 10 clinical studies on 681 patients (TIMERS component: E) revealing improved hemostasis and healing of military or civilian full- or partial-thickness acute or chronic wounds including SGDSs, diabetic foot ulcers, pressure injuries, venous ulcers, and oral surgery sites.38,39


Carrageenan searches returned no clinical studies reporting any clinical benefit related to wound healing. This agent was mainly used in preclinical studies as a pain- or inflammation-inducing agent in rodents or a primer for liver or lung endotoxin shock studies in vivo.40


Curcumin, also called diferuloylmethane, was surveyed in 11 clinical studies on 1,227 patients (TIMERS component: I) and reduced radiation mucositis, dermatitis, or periodontal inflammation when delivered orally or as a topical gel often encapsulated in liposomes.41,42 Considerable preclinical research has been conducted to develop a formulation with adequate solubility and systemic absorption to optimize its safe delivery and efficacy in wound management.43


Dextran, involved in 16 studies on 9,519 patients (TIMERS components: T, I), was used as a topical dextranomer powder to heal chronic wounds or burns.44,45 Adding 6% dextran-70 (70,000 molecular weight) administered infusion to lactated Ringer's solution was more effective than lactated Ringer's solution alone in preventing acute respiratory distress syndrome and improving low BP associated with shock in trauma patients en route to the hospital.46 However, later studies reported that hypertonic saline (7.5%) prevented posttraumatic hypotension as effectively without adding dextran-70.47 To prevent postsurgical deep vein thrombosis (DVT), 500 to 1,000 mL of dextran-40 or dextran-70 during the first 2 to 6 hours postoperatively, followed by 500 mL per day for 1 week, was effective in preventing DVT compared with 0% dextran. However, researchers reported the possibility that dextran may worsen progressive hypercoagulation in these trauma patients.48 Dextran infusions prevented more postsurgical hematomas than low-molecular-weight heparin, whereas heparin interventions limited more DVTs than dextran did. Topical treatment of chronic wounds with dextranomer paste was less effective in healing sloughy pressure injuries than similar treatment with an amorphous hydrogel.49 In general, dextran polymer formulations showed initial promise in emergency resuscitation and preventing postsurgical DVT, as well as debriding chronic wounds, but their efficacy and safety were exceeded by other agents in at least 18 subsequent RCTs.


Gelatin was used in 20 studies on 1,560 patients (TIMERS component: E). It was typically applied as a foam sponge drug delivery system or to aid in hemostasis or healing of ruptured tympanic membrane50 or as a packing agent following nasal,51 sinus,52 or other surgery. It was often combined with collagen or fibrin glue to deliver growth factors or other agents in studies excluded from this analysis because the effects of the gelatin per se were unclear. The efficacy of other agents exceeded gelatin as a posttraumatic infusion in reducing capillary leakage. As a sealant for vascular prostheses, gelatin transiently increased circulating leukocytes for 2 weeks after grafting without other notable adverse effects.53 Gelatin can be used as an acceptable absorbable hemostatic sponge,54 but if left in place after the removal of thyroid cancer, it may mimic residual or recurrent thyroid carcinoma during follow-up ultrasound surveillance.55 When injected into individuals with severe brain trauma, gelatin solutions improved intracranial pressure, Glasgow Coma Scale scores at 1 to 2 weeks, and 3-month Glasgow Outcome Scale scores compared with traditional management.56


Two studies on 139 patients involved ginseng (TIMERS component: I) saponin glycosides administered with peripheral blood monocytes improved circulation measures and 6-minute walking distance of patients with critical limb ischemia compared with peripheral blood monocytes administered alone. It was often included in complex Chinese traditional medicine formulations, but its effects in these were unclear. It has been reported to protect against myocardial ischemia-reperfusion injury,57 but anabolic effects during or after exercise have not been confirmed in an RCT.58 Researchers have raised concerns that patients taking unreported botanic supplements such as ginseng, ginkgo biloba, garlic, ginger, valerian, kava, St John's wort, ephedra, or echinacea may experience unforeseen serious complications during surgery.59


Glucan, derived from yeast cell walls or certain mushrooms, was licensed as a drug in Japan in 1983. This review included 5 studies on 1,363 patients using glucan (TIMERS components: I, E). Most of its clinical trials combined a glucan with a monoclonal antibody to limit cancer metastases, improve gastrointestinal disorder outcomes, lower cholesterol, or address immune disorders, all of which are beyond the scope of this review.60 Further, [beta]-glucans have been reported to modulate inflammation, coagulation abnormalities, and digestive disorders associated with COVID-19.61 In critically ill patients with trauma wounds, high-protein parenteral supplements with [beta]-1,3-glucans reduced pneumonia, sepsis, organ failure, and ventilator time.62,63 Further, 1.4 g daily doses of [beta]-1,3/1,6-glucan for 5 days preceding coronary artery bypass graft surgery reduced ischemia-reperfusion injury.64 Oral 0.5 mg/kg of yeast-cell-wall PGG glucan (one dose preoperatively and three doses postoperatively) reduced the incidence of serious postoperative infections or death following noncolorectal surgery in high-risk patients, but was associated with adverse events in colorectal surgery.65 Finally, topical use of water-insoluble [beta]-1,3-glucan purified from baker's yeast (Saccharomyces cerevisiae) was associated with venous ulcer healing in one case series.66


Green tea is derived from the tea tree Melaleuca alternifolia. Five studies on 264 patients (TIMERS component: I) reported on green tea. Its catechins had antimicrobial properties and anti-inflammatory effects on the cyclooxygenase and lipoxygenase eicosanoid pathways, but when taken orally (1,080 mg of catechins in 1,350 mg of green tea extract with 50 mg of vitamin C per day) for 3 months did not reduce skin erythema, leukocyte response, or eicosanoid responses to a UV light inflammatory challenge. Pretreating skin with green tea polyphenol extracts protected volunteers' skin from sun damage.67 If applied within 30 minutes after thermal burns, a green tea extract spray reduced burn pain, but water cooled the burned skin more68 and was similarly effective in treating postpartum nipple pain.69


Two studies on 100 patients (TIMERS components: I, E) discussed henna. Henna derived from Lawsonia inermis improved healing and pain when applied topically to episiotomies compared with placebo.70 In an ointment formulation, it improved healing, pain, pruritus, and discharge of radiation dermatitis sites when applied immediately after 45 to 50 Gy radiotherapy compared with a similar application of 1% hydrocortisone cream.


Honey was the most well-studied alternative agent in this review; investigators noted 32 clinical studies on 2,147 patients (TIMERS components: T, I, M, E). Honey is a humectant made by honeybees. Trials on a wide variety of acute surgical, trauma, or burn wounds; radiation-induced mucositis;71 and chronic pressure injuries, venous leg ulcers, or diabetic foot ulcers support the promotion of a moist wound healing environment, improved healing, and better debridement or wound infection outcomes with a variety of honey sources.72 These results have been confirmed by independent systematic reviews on various etiologies of acute or chronic wounds.73-75


Marigold (Tagetes) and Calendula (Calendula) are both in the Asteracea family and not always distinguished from one another in the literature. These researchers noted 9 clinical studies on 960 patients (TIMERS components: I, E). Calendula ointment shortened the inflammation phase of acute healing and improved radiation dermatitis,76 similar to the effects of aqueous cream, and had mixed effects on chronic venous or diabetic ulcers or acute burn wounds.36 In gynecologic surgery, Calendula ointment improved episiotomy healing and pain or cesarean section healing compared with standard of care.77,78


Neem (Azadirachta indica) returned no studies where it was applied to wounds alone as a topical or systemic intervention. It was often combined with other topical wound treatments such as turmeric. This reduced the clarity of its effects in wound care.


Pectin, a hydrocolloid substance derived from fruit, was examined in 5 clinical studies on 167 patients (TIMERS components: M, E). It was often combined with other agents or mixed with other biopolymers to add moist-adherent properties to skin or wound adhesives. Pectin was applied as a skin barrier to prevent or heal tape damage on peristomal areas or near tracheostomy sites79 or to protect the delicate intact facial skin of premature infants.80


Polycaprolactone was frequently studied as a "bio-ink" for three-dimensional printing of tissue scaffolds or as a delivery system for other agents or sensors.81 Repeated searches found no clinical studies of its effects on any human skin wound.


Polylactic acid (PLA; 9 studies on 248 patients; TIMERS component: E) may foster periodontal, cleft palate, or tendon healing. The SGDSs dressed with a PLA copolymer dressing healed similarly to those dressed with a cellulose nanofiber dressing with comparable pain, but the PLA dressed wounds had thicker, less elastic scars 1 month postoperatively.82 When used to guide flexor tendon repair, PLA membranes reduced adhesions, improving interphalangeal joint function compared with untreated sites, as did freeze-dried amniotic membranes, but PLA elicited more complications.83 The use of bioabsorbable PLA screws instead of metallic screws proved reliable and effective for ankle fracture fixation, avoiding a second surgery to remove metallic screws, with similar results for PLA rotator cuff anchors, but using PLA knee joint fixation screws was associated with complications including bone resorption.84 Most studies on PLA-bone screw interactions were excluded from this work unless they also pertained to skin wounds.


Polyethylene glycol (PEG) was included in 13 studies involving 1,171 patients (TIMERS components: T, I, M). Certain PEG hydrogels have been reported to be effective in preventing surgical adhesion as a topical debriding agent or as a dural sealant after spinal surgery.85 When used before radiation therapy to expand space between prostate cancer and the bowel, it has reduced adverse effects of radiation. Its use in presurgery bowel preparation reduced electrolyte disturbance for elective colorectal procedures with mixed efficacy.86,87


Polyurethane film or foam was mentioned in 25 studies on 1,565 patients (TIMERS components: I, M, E). It was reported to prevent pressure injury development in older adults recovering from hip fractures. Resorbable polyurethane used as postoperative nasal packing improved endoscopic sinus surgery outcomes. Postsurgical polyurethane wound drains reduced thrombus formation and pain on removal compared with polyvinyl chloride drains;88 further, polyurethane adhesive removed and reapplied every 48 hours did not damage periwound skin around venous leg ulcers as much as hydrocolloid adhesive wound dressings did.89 Adhesive wound dressings with a polyurethane film or foam backing reduced healing time, pain, and infection rates in surgical sites, acute wounds, or chronic wounds compared with gauze dressings.90-92 Evidence on dressings where a polyurethane foam or adhesive was used at the wound interface is summarized in Figure 2.


Rosemary (Rosmarinus officinalis) is an evergreen shrub from South America and the Mediterranean coast with preclinical evidence of antioxidant, anti-inflammatory, anticancer, and antihyperglycemic properties.93 No studies were found supporting its effects on patients with wounds. Ursolic acid extracted from rosemary (150 mg once daily for 12 weeks) lowered body mass index, weight, waist circumference, and fasting glucose and increased insulin sensitivity in 12 patients with diabetes mellitus compared with a placebo,94 but effects on wounds were not studied.



This scoping review suggests that many naturally derived agents previously categorized as "alternative practice" merit consideration given their potential to improve wound outcomes. Those backed by evidence from at least 10 RCTs include honey, alginate gel or fiber dressings, polyurethane gel or adhesive dressings, aloe vera gel, and dextran powder. Some of these have already entered the ranks of agents or delivery systems used in clinical practice, been cleared by regulatory authorities for mainstream clinical use, and drawn the attention of Cochrane or other reviewers. Opportunities abound for improvements in managing hemostasis, scarring, or adhesions. These agents may support recognized aspects of healing such as fibroplasia, angiogenesis, and epithelialization; improve wound inflammation, infection, and pain; or maintain moisture balance to minimize the need for frequent dressing changes. Further clinical research is needed to determine if these alternative agents improve outcomes compared with current standard of practice, either combined with current products or as adjunct interventions.


This review limited itself to the agents with which the authors were familiar. Other alternative agents in use elsewhere in the world may merit similar reviews and/or clinical studies.



The preclinical evidence and clinical literature reviewed suggest that honey, alginate gels or fiber dressings, polyurethane gel or adhesive dressings, aloe vera gel, and dextran powder have clinical evidence of potential efficacy in wound management. Many other alternative agents are supported by sufficient clinical research to suggest their potential as smart excipients or novel active agents within future multifaceted wound management delivery systems.




Ten or more RCTs support continued research and practice using honey, alginate gel or fiber dressings, polyurethane gel or adhesive dressings, aloe vera gel, or dextran powder on various clinical wounds.


* Several agents previously considered "alternative" are now cleared by regulatory authorities and have become mainstream wound care treatments. These agents may improve wound hemostasis, inflammation, infection, pain, angiogenesis, fibroplasia, and epithelialization.


* Substantial research suggests that alternative products have potential as smart excipients or novel active agents within future multifaceted wound management delivery systems.


* Exploring these and other alternative wound management agents may have the potential to improve outcomes for patients with wounds.




1. Weiser TG, Haynes AB, Molina G, et al. Size and distribution of the global volume of surgery in 2012. Bull World Health Organ2016;94(3):201-9F. [Context Link]


2. World Health Organization. Fact sheet on Burns. 2018. Last accessed July 27, 2021. [Context Link]


3. Nussbaum SR, Carter MJ, Fife CE, et al. An economic evaluation of the impact, cost, and Medicare policy implications of chronic nonhealing wounds. Value Health2018;21(1):27-32. [Context Link]


4. Young A, McNaught C-E. The physiology of wound healing. Surg2011;29(10):475-9. [Context Link]


5. Gantwerker EA, Hom DB. Skin: histology and physiology of wound healing. Facial Plast Surg Clin North Am2011;19(3):441-53. [Context Link]


6. Lazarus GS, Cooper DM, Knighton DR, et al. Definitions and guidelines for assessment of wounds and evaluation of healing. Arch Dermatol1994;130(4):489-93. [Context Link]


7. Hosseinkhani A, Falahatzadeh M, Raoofi E, Zarshenas MM. An evidence-based review on wound healing herbal remedies from reports of traditional Persian medicine. J Evid Based Complement Altern Med2017;22(2):334-43. [Context Link]


8. Kumar B, Vijayakumar M, Govindarajan R, Pushpangadan P. Ethnopharmacological approaches to wound healing-exploring medicinal plants of India. J Ethnopharmacol2007;114(2):103-13. [Context Link]


9. Saini S, Dhiman A, Nanda S. Traditional Indian medicinal plants with potential wound healing activity: a review. Int J Pharm Sci Res2016;1809-19. [Context Link]


10. Dai X, Liu J, Zheng H, et al. Nano-formulated curcumin accelerates acute wound healing through Dkk-1-mediated fibroblast mobilization and MCP-1-mediated anti-inflammation. NPG Asia Mater2017;9(3):e368. [Context Link]


11. El-Refaie WM, Elnaggar YSR, El-Massik MA, Abdallah OY. Novel curcumin-loaded gel-core hyaluosomes with promising burn-wound healing potential: development, in-vitro appraisal and in-vivo studies. Int J Pharm2015;486(1-2):88-98. [Context Link]


12. Kosalwatna S, Shaipanich C, Bhanganada K. The effect of one percent Centella asiatica cream on chronic ulcers. Siriraj Med J1988;40(6):455-61. [Context Link]


13. Shukla A, Rasik AM, Dhawan BN. Asiaticoside-induced elevation of antioxidant levels in healing wounds. Phyther Res1999;13(1):50-4. [Context Link]


14. Hekmatpou D, Mehrabi F, Rahzani K, et al. The effect of aloe vera clinical trials on prevention and healing of skin wound: a systematic review. Iran J Med Sci2019;44(1):1-9. [Context Link]


15. Ilango K, Maharajan G, Narasimhan S. Anti-nociceptive and anti-inflammatory activities of Azadirachta indica fruit skin extract and its isolated constituent azadiradione. Nat Prod Res2013;27(16):1463-7. [Context Link]


16. Maver T, Maver U, Stana Kleinschek K, Smrke DM, Kreft S. A review of herbal medicines in wound healing. Int J Dermatol2015;54(7):740-51. [Context Link]


17. Alizargar J, Kuchaki E, Shaabani A, Namazi M. Properties of wound healing activities of rosemary extract. J Biol Act Prod Nat2012;2(4):218-24. [Context Link]


18. Hajiaghaalipour F, Kanthimathi MS, Abdulla MA, Sanusi J. The effect of Camellia sinensis on wound healing potential in an animal model. Evid Based Complement Altern Med2013;2013:386734. [Context Link]


19. Fatemi MJ, Nikoomaram B, Rahimi AAK, Talayi D, Taghavi S, Ghavami Y. Effect of green tea on the second degree burn wounds in rats. Indian J Plast Surg2014;47(3):370-4. [Context Link]


20. Hadisi Z, Nourmohammadi J, Nassiri SM. The antibacterial and anti-inflammatory investigation of Lawsonia inermis-gelatin-starch nano-fibrous dressing in burn wound. Int J Biol Macromol2018;107(pt B):2008-19. [Context Link]


21. Gad HA, Abd El-Rahman FAA, Hamdy GM. Chamomile oil loaded solid lipid nanoparticles: a naturally formulated remedy to enhance the wound healing. J Drug Deliv Sci Technol2019;50:329-38. [Context Link]


22. Dorai AA. Wound care with traditional, complementary and alternative medicine. Indian J Plast Surg2012;45(2):418-24. [Context Link]


23. Harries RL, Bosanquet DC, Harding KG. Wound bed preparation: TIME for an update. Int Wound J2016;13(S3):8-14. [Context Link]


24. Lim K, Free B, Sinha S. Modified TIME-H: a simplified scoring system for chronic wound management. J Wound Care2015;24(9):415-9. [Context Link]


25. Beitz J. Using wound care algorithms: a content validation study. J Wound Ostomy Continence Nurs1999;26(5):238-49. [Context Link]


26. Bolton L, McNees P, van Rijswijk L, et al. Wound-healing outcomes using standardized assessment and care in clinical practice. J Wound Ostomy Continence Nurs2004;31(2):65-71. [Context Link]


27. Driver VR, Gould LJ, Dotson P, et al. Identification and content validation of wound therapy clinical endpoints relevant to clinical practice and patient values for FDA approval. Part 1. Survey of the wound care community. Wound Repair Regen2017;25(3):454-65. [Context Link]


28. Brolmann FE, Eskes AM, Goslings JC, et al. Randomized clinical trial of donor-site wound dressings after split-skin grafting. Br J Surg2013;100(5):619-27. [Context Link]


29. Norman G, Westby MJ, Rithalia AD, Stubbs N, Soares MO, Dumville JC. Dressings and topical agents for treating venous leg ulcers. Cochrane Database Syst Rev2018;6(6):CD012583. [Context Link]


30. Dumville JC, O'Meara S, Deshpande S, Speak K. Alginate dressings for healing diabetic foot ulcers. Cochrane Database Syst Rev2013;(6):CD009110. [Context Link]


31. Westby MJ, Dumville JC, Soares MO, Stubbs N, Norman G. Dressings and topical agents for treating pressure ulcers. Cochrane Database Syst Rev2017;6(6):CD011947. [Context Link]


32. Beam JW. Topical silver for infected wounds. J Athl Train2009;44(5):531-3. [Context Link]


33. Woo KY, Coutts PM, Sibbald RG. A randomized controlled trial to evaluate an antimicrobial dressing with silver alginate powder for the management of chronic wounds exhibiting signs of critical colonization. Adv Skin Wound Care2012;25(11):503-8. [Context Link]


34. Norman G, Christie J, Liu Z, et al. Antiseptics for burns. Cochrane Database Syst Rev2017;7:CD011821. [Context Link]


35. Moore ZE, Cowman S. Wound cleansing for pressure ulcers. Cochrane Database Syst Rev2013;2013(3):CD004983. [Context Link]


36. Givol O, Kornhaber R, Visentin D, Cleary M, Haik J, Harats M. A systematic review of Calendula officinalis extract for wound healing. Wound Repair Regen2019;27(5):548-61. [Context Link]


37. Muangman P, Praditsuktavorn B, Chinaroonchai K, Chuntrasakul C. Clinical efficacy test of polyester containing herbal extract dressings in burn wound healing. Int J Low Extrem Wounds2016;15(3):203-12. [Context Link]


38. Malmquist JP, Clemens SC, Oien HJ, Wilson SL. Hemostasis of oral surgery wounds with the HemCon dental dressing. J Oral Maxillofac Surg2008;66(6):1177-83. [Context Link]


39. Kircik LH. Comparative study of the efficacy and tolerability of a unique topical scar product vs white petrolatum following shave biopsies. J Drugs Dermatol2013;12(1):86-90. [Context Link]


40. Camara CC, Ramos HF, da Silva AP, et al. Oral gabapentin treatment accentuates nerve and peripheral inflammatory responses following experimental nerve constriction in Wistar rats. Neurosci Lett2013;556:93-8. [Context Link]


41. Farhood B, Mortezaee K, Goradel NH, et al. Curcumin as an anti-inflammatory agent: Implications to radiotherapy and chemotherapy. J Cell Physiol2019;234(5):5728-40. [Context Link]


42. Xu H, Gong Z, Zhou S, et al. Liposomal curcumin targeting endometrial cancer through the NF-[kappa]B pathway. Cell Physiol Biochem2018;48(2):569-82. [Context Link]


43. Nguyen M-H, Lee SE, Tran T-T, et al. A simple strategy to enhance the in vivo wound-healing activity of curcumin in the form of self-assembled nanoparticle complex of curcumin and oligochitosan. Mater Sci Eng C2019;98:54-64. [Context Link]


44. Ljungberg S. Comparison of dextranomer paste and saline dressings for management of decubital ulcers. Clin Ther1998;20(4):737-43. [Context Link]


45. Hulkko A, Holopainen YV, Orava S, et al. Comparison of dextranomer and streptokinase-streptodornase in the treatment of venous leg ulcers and other infected wounds. Ann Chir Gynaecol1981;70(2):65-70. [Context Link]


46. Vassar MJ. 7.5% Sodium chloride/dextran for resuscitation of trauma patients undergoing helicopter transport. Arch Surg1991;126(9):1065. [Context Link]


47. Vassar MJ, Perry CA, Holcroft JW. Prehospital resuscitation of hypotensive trauma patients with 7.5% NaCl versus 7.5% NaCl with added dextran: a controlled trial. J Trauma1993;34(5):622-32. [Context Link]


48. Delano MJ, Rizoli SB, Rhind SG, et al. Prehospital resuscitation of traumatic hemorrhagic shock with hypertonic solutions worsens hypocoagulation and hyperfibrinolysis. Shock2015;44(1):25-31. [Context Link]


49. Colin D, Kurring PA, Quinlan D, Yvon C. Managing sloughy pressure sores. J Wound Care1996;5(10):444-6. [Context Link]


50. Lou Z-C, Wei H, Lou Z-H. Comparison of the medical costs and effects of large traumatic eardrum perforations treatment. Am J Otolaryngol2019;40(1):46-51. [Context Link]


51. Kim S-D, Hong S-L, Kim M-J, et al. Effectiveness of hemostatic gelatin sponge as a packing material after septoplasty: a prospective, randomized, multicenter study. Auris Nasus Larynx2018;45(2):286-90. [Context Link]


52. Cho K-S, Park C-H, Hong S-L, et al. Comparative analysis of Cutanplast and Spongostan nasal packing after endoscopic sinus surgery: a prospective, randomized, multicenter study. Eur Arch Otorhinolaryngol2015;272(7):1699-1705. [Context Link]


53. Utoh J, Goto H, Hirata T, Hara M, Kitamura N. Postoperative inflammatory reactions to sealed Dracon prostheses: a comparison of Gelseal and Hemashield. J Cardiovasc Surg (Torino)1997;38(3):287-90. [Context Link]


54. Rossmann JA, Rees TD. A comparative evaluation of hemostatic agents in the management of soft tissue graft donor site bleeding. J Periodontol1999;70(11):1369-75. [Context Link]


55. Tublin ME, Alexander JM, Ogilvie JB. Appearance of absorbable gelatin compressed sponge on early post-thyroidectomy neck sonography. J Ultrasound Med2010;29(1):117-20. [Context Link]


56. Ai W, Chen Y, Yang Q. [Clinical observation on effect of xuesaitong injection as auxiliary treatment of severe craniocerebral injury]. Chinese J Integr Tradit West Med2004;24(3):213-5. [Context Link]


57. Zhan Y, Xu XH, Jiang YP. [Protective effects of ginsenoside on myocardiac ischemic and reperfusion injuries]. Zhonghua Yi Xue Za Zhi1994;74(10):626-8. [Context Link]


58. Youl Kang H, Hwan Kim S, Jun Lee W, Byrne HK. Effects of ginseng ingestion on growth hormone, testosterone, cortisol, and insulin-like growth factor 1 responses to acute resistance exercise. J Strength Cond Res2002;16(2):179-83. [Context Link]


59. Ciocon JO, Ciocon DG, Galindo DJ. Dietary supplements in primary care. Botanicals can affect surgical outcomes and follow-up. Geriatrics2004;59(9):20-4. [Context Link]


60. Vetvicka V, Vannucci L, Sima P, Richter J. Beta glucan: supplement or drug? From laboratory to clinical trials. Molecules2019;24(7). [Context Link]


61. Jawhara S. How to boost the immune defence prior to respiratory virus infections with the special focus on coronavirus infections. Gut Pathog2020;12(1):47. [Context Link]


62. de Felippe Junior J, da Rocha e Silva Junior M, Maciel FM, Soares A de M, Mendes NF. Infection prevention in patients with severe multiple trauma with the immunomodulator beta 1-3 polyglucose (glucan). Surg Gynecol Obstet1993;177(4):383-8. [Context Link]


63. Fazilaty Z, Chenari H, Shariatpanahi ZV. Effect of [latin sharp s]-glucan on serum levels of IL-12, hs-CRP, and clinical outcomes in multiple-trauma patients: a prospective randomized study. Ulus Travma Acil Cerrahi Derg2018;24(4):287-93. [Context Link]


64. Aarsaether E, Rydningen M, Einar Engstad R, Busund R. Cardioprotective effect of pretreatment with [beta]-glucan in coronary artery bypass grafting. Scand Cardiovasc J2006;40(5):298-304. [Context Link]


65. Dellinger EP, Babineau TJ, Bleicher P, et al. Effect of PGG-glucan on the rate of serious postoperative infection or death observed after high-risk gastrointestinal operations. Betafectin Gastrointestinal Study Group. Arch Surg1999;134(9):977-83. [Context Link]


66. Medeiros SDV, Cordeiro SL, Cavalcanti JEC, et al. Effects of purified Saccharomyces cerevisiae (1 -> 3)-[beta]-glucan on venous ulcer healing. Int J Mol Sci2012;13(7):8142-58. [Context Link]


67. Elmets CA, Singh D, Tubesing K, Matsui M, Katiyar S, Mukhtar H. Cutaneous photoprotection from ultraviolet injury by green tea polyphenols. J Am Acad Dermatol2001;44(3):425-32. [Context Link]


68. Cho YS, Choi YH. Comparison of three cooling methods for burn patients: a randomized clinical trial. Burns2017;43(3):502-8. [Context Link]


69. National Library of Medicine. Drugs and Lactation Database (LactMed). Green Tea. Bethesda MD; National Library of Medicine; 2018. [Context Link]


70. Zibanejad S, Miraj S, Rafieian Kopaei M. Healing effect of Quercus persica and Lawsonia inermis ointment on episiotomy wounds in primiparous women. J Res Med Sci2020;25:11. [Context Link]


71. Song JJ, Twumasi-Ankrah P, Salcido R. Systematic review and meta-analysis on the use of honey to protect from the effects of radiation-induced oral mucositis. Adv Skin Wound Care2012;25(1):23-8. [Context Link]


72. Yilmaz AC, Aygin D. Honey dressing in wound treatment: a systematic review. Complement Ther Med2020;51:102388. [Context Link]


73. Wang C, Guo M, Zhang N, Wang G. Effectiveness of honey dressing in the treatment of diabetic foot ulcers: a systematic review and meta-analysis. Complement Ther Clin Pract2019;34:123-31. [Context Link]


74. Brolmann FE, Ubbink DT, Nelson EA, Munte K, van der Horst CMAM, Vermeulen H. Evidence-based decisions for local and systemic wound care. Br J Surg2012;99(9):1172-83. [Context Link]


75. Norman G, Christie J, Liu Z, et al. Antiseptics for burns. Cochrane Database Syst Rev2017;7(7):CD011821. [Context Link]


76. Kassab S, Cummings M, Berkovitz S, van Haselen R, Fisher P. Homeopathic medicines for adverse effects of cancer treatments. Cochrane Database Syst Rev2009;(2):CD004845. [Context Link]


77. De Angelis C, Di Stadio A, Vitale S, et al. Use of calendula ointment after episiotomy: a randomized clinical trial. J Matern Fetal Neonatal Med2020:1-5. [Context Link]


78. Jahdi F, Khabbaz AH, Kashian M, Taghizadeh M, Haghani H. The impact of calendula ointment on cesarean wound healing: a randomized controlled clinical trial. J Fam Med Prim Care7(5):893-7. [Context Link]


79. Chuang W-L, Huang W-P, Chen M-H, Liu I-P, Yu W-L, Chin C-C. Gauze versus solid skin barrier for tracheostomy care: a crossover randomized clinical trial. J Wound Ostomy Continence Nurs2013;40(6):573-9. [Context Link]


80. Dollison EJ, Beckstrand J. Adhesive tape vs pectin-based barrier use in preterm infants. Neonatal Netw1995;14(4):35-9. [Context Link]


81. Farzanfar S, Kouzekonan GS, Mirjani R, Shekarchi B. Vitamin B12-loaded polycaprolacton/gelatin nanofibrous scaffold as potential wound care material. Biomed Eng Lett2020;10(4):547-54. [Context Link]


82. Koivuniemi R, Hakkarainen T, Kiiskinen J, et al. Clinical study of nanofibrillar cellulose hydrogel dressing for skin graft donor site treatment. Adv Wound Care2020;9(4):199-210. [Context Link]


83. Liu C, Bai J, Yu K, Liu G, Tian S, Tian D. Biological amnion prevents flexor tendon adhesion in zone II: a controlled, multicentre clinical trial. Biomed Res Int2019;2019:1-9. [Context Link]


84. Drogset JO, Straume LG, Bjorkmo I, Myhr G. A prospective randomized study of ACL-reconstructions using bone-patellar tendon-bone grafts fixed with bioabsorbable or metal interference screws. Knee Surg Sports Traumatol Arthrosc2011;19(5):753-9. [Context Link]


85. Wright NM, Park J, Tew JM, et al. Spinal sealant system provides better intraoperative watertight closure than standard of care during spinal surgery: a prospective, multicenter, randomized controlled study. Spine (Phila Pa 1976)2015;40(8):505-13. [Context Link]


86. Fa-Si-Oen P, Roumen R, Buitenweg J, et al. Mechanical bowel preparation or not? Outcome of a multicenter, randomized trial in elective open colon surgery. Dis Colon Rectum2005;48(8):1509-16. [Context Link]


87. Ancha HR, Spungen AM, Bauman WA, et al. Clinical trial: the efficacy and safety of routine bowel cleansing agents for elective colonoscopy in persons with spinal cord injury-a randomized prospective single-blind study. Aliment Pharmacol Ther2009;30(11-12):1110-7. [Context Link]


88. Gerngross H, Willy C, Walter WM. [Experimental and clinical studies of the use of thin-lumen polyurethane gravity drainage in accident surgery]. Unfallchirurg1992;95(1):21-30. [Context Link]


89. Zillmer R, Agren MS, Gottrup F, Karlsmark T. Biophysical effects of repetitive removal of adhesive dressings on peri-ulcer skin. J Wound Care2006;15(5):187-91. [Context Link]


90. Brolmann FE, Eskes AM, Goslings JC, et al. Randomized clinical trial of donor-site wound dressings after split-skin grafting. Br J Surg2013;100(5):619-27. [Context Link]


91. Hutchinson JJ, McGuckin M. Occlusive dressings: a microbiologic and clinical review. Am J Infect Control1990;18(4):257-68. [Context Link]


92. Arroyo AA, Casanova PL, Soriano JV, Torra i Bou J-E. Open-label clinical trial comparing the clinical and economic effectiveness of using a polyurethane film surgical dressing with gauze surgical dressings in the care of post-operative surgical wounds. Int Wound J2015;12(3):285-92. [Context Link]


93. Naimi M, Vlavcheski F, Shamshoum H, Tsiani E. Rosemary extract as a potential anti-hyperglycemic agent: current evidence and future perspectives. Nutrients2017;9(9). [Context Link]


94. University of Guadalajara. Effect of Ursolic Acid Administration on Insulin Sensitivity and Metabolic Syndrome. 2020. Last accessed July 27, 2021. [Context Link]