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Objective: To investigate the effects of expressive writing and its timing (pre or post wounding) on re-epithelialisation and leucocyte subsets within healing tissue. We previously showed expressive writing pre-wounding improved re-epithelialisation. Here we investigate cellular processes in the wound., Methods: In a 2(writing content) x 2(writing timing) randomized trial, 122 participants were randomized to perform either expressive or control writing, before or after a 4 mm punch biopsy wound. On day 14 post-wounding, participants had a 5 mm punch biopsy of the initial wound. Seven of 16 primary registered outcomes were analysed, including re-epithelialisation from two photographs of the 4 mm biopsy (previously reported). This paper reports immunohistochemistry analysis of five primary outcomes - Langerhans cells, immune cell activation (HLA and CD3+), and macrophages (CD68 and MPO) - in the 5 mm biopsies in a random sample of 96 participants., Results: Participants who performed either writing task pre-wounding had greater Langerhans cell infiltration, than those who wrote post-wounding (F (1,85)  = 7.86, p = .006, η p 2  = 0.08). Those who performed expressive writing also had greater Langerhans cell infiltration than those who performed control writing (F (1,85)  = 4.00, p = .049, η p 2  = 0.04). There were no significant group or interaction effects on immune cell activation or macrophages. Healed wounds on day 10 had lower levels of macrophages (z = -1.96, p = .050), and CD3+ cells (z = -1.99, p = .046) than non-healed wounds., Conclusion: Langerhans cells in the healing skin are affected by the timing and topic of writing. More research is needed to further explore timing and corroborate these results., Clinical Trials Registration: Registered at https://www.anzctr.org.au/ (Trial ID: ACTRN12614000971639)., Competing Interests: Declaration of Competing Interest The authors have no competing interests to report., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Open-label placebos are a novel treatment option, in which participants take placebos with full knowledge that they do not contain active medicine. Open-label placebo treatments have been shown to result in patient-reported symptom improvements, but they have not been tested on objectively measurable physiological outcomes such as wound healing., Purpose: The current study aimed to determine whether open-label placebos improved wound healing in punch biopsy wounds compared with no treatment., Methods: In a randomized controlled trial, 70 participants (mean age 27.6 ± 10.1, 58 female) were provided with information about the beneficial effects of placebos and given a 4 mm punch biopsy wound. Participants were then randomized to either an open-label placebo intervention (two placebo tablets twice a day for 10 days) or a no-treatment control group. Wounds were photographed at 7 days and 10 days to determine reepithelialization of the wound surface., Results: No significant differences were observed between the open-label placebo and control conditions in the percentage of wound area healed or for the number of participants with fully reepithelialized wounds at 7 days (placebo 7/32 wounds healed, control 10/33 wounds healed, (χ2[1, N = 65] = 0.60, p = .440, φ = 0.10) and 10 days after wounding (placebo 17/32, control 25/33 wounds healed (χ2[1, N = 65] = 3.64, p = .056, φ = 0.24)., Conclusions: Open-label placebo treatment does not improve the healing rate of wounds. Open-label placebos may be beneficial for subjective patient-reported outcomes but do not influence wound healing., Australian New Zealand Clinical Trials Registration: ACTRN12616000411448.

Purpose: Psychological stress has been shown to delay wound healing. Several trials have investigated whether psychological interventions can improve wound healing, but to date, this evidence base has not been systematically synthesized. The objective was to conduct a systematic review of randomized controlled trials in humans investigating whether psychological interventions can enhance wound healing., Methods: A systematic review was performed using PsychINFO, CINAHL, Web of Science, and MEDLINE. The searches included all papers published in English up until September 2016. The reference lists of relevant papers were screened manually to identify further review articles or relevant studies. Nineteen studies met inclusion criteria and were included in the review., Results: Fifteen of nineteen studies were of high methodological quality. Six studies were conducted with acute experimentally created wounds, five studies with surgical patients, two studies with burn wounds, two studies with fracture wounds, and four studies were conducted with ulcer wounds. Post-intervention standardized mean differences (SMD) between groups across all intervention types ranged from 0.13 to 3.21, favouring improved healing, particularly for surgical patients and for relaxation interventions. However, there was some evidence for publication bias suggesting negative studies may not have been reported. Due to the heterogeneity of wound types, population types, and intervention types, it is difficult to pool effect sizes across studies., Conclusions: Current evidence suggests that psychological interventions may aid wound healing. Although promising, more research is needed to assess the efficacy of each intervention on different wound types. Statement of contribution What is already known on this subject? Psychological stress negatively affects wound healing. A number of studies have investigated whether psychological interventions can improve healing. However, no systematic reviews have been conducted. What does this study add? Synthesis and review of 19 trials conducted on psychological interventions and wound healing. Most evidence supports improved healing, particularly for surgical wounds and relaxation interventions. More research is needed on different intervention types with clinical wounds and into mechanisms of action., (© 2017 The British Psychological Society.)

Objective: Writing emotionally about upsetting life events (expressive writing) has been shown to speed healing of punch-biopsy wounds compared to writing objectively about daily activities. We aimed to investigate whether a presurgical expressive writing intervention could improve surgical wound healing., Method: Seventy-six patients undergoing elective laparoscopic bariatric surgery were randomized either to write emotionally about traumatic life events (expressive writing) or to write objectively about how they spent their time (daily activities writing) for 20 min a day for 3 consecutive days beginning 2 weeks prior to surgery. A wound drain was inserted into a laparoscopic port site and wound fluid analyzed for proinflammatory cytokines collected over 24 hr postoperatively. Expanded polytetrafluoroethylene tubes were inserted into separate laparoscopic port sites during surgery and removed after 14 days. Tubes were analyzed for hydroxyproline deposition (the primary outcome), a major component of collagen and marker of healing. Fifty-four patients completed the study., Results: Patients who wrote about daily activities had significantly more hydroxyproline than did expressive writing patients, t(34) = -2.43, p = .020, 95% confidence interval [-4.61, -0.41], and higher tumor necrosis factor-alpha, t(29) = -2.42, p = .022, 95% confidence interval [-0.42, -0.04]. Perceived stress significantly reduced in both groups after surgery., Conclusions: Expressive writing prior to bariatric surgery was not effective at increasing hydroxyproline at the wound site 14 days after surgery. However, writing about daily activities did predict such an increase. Future research needs to replicate these findings and investigate generalizability to other surgical groups. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Objective: Recent studies have shown that written emotional disclosure (expressive writing) performed in the two weeks prior to wounding improves healing of punch biopsy wounds. In many clinical settings, it would be more practical for patients to perform this intervention after wounding. The aim of this study was to investigate whether expressive writing could speed the healing of punch biopsy wounds if writing was performed after wounds were made., Methods: One hundred and twenty-two healthy participants aged between 18 and 55years were randomly allocated to one of four groups in a 2 (intervention) by 2 (timing) design. Participants performed either expressive writing or neutral writing, either before or after receiving a 4mm punch biopsy wound. Wounds were photographed on day 10 (primary endpoint) and day 14 after the biopsy to measure epithelisation. Participants also completed questionnaires on stress and affect two weeks prior to the biopsy, on the day of biopsy and two weeks after biopsy., Results: There was a significant difference in healing at day 10 between groups, χ 2 (3, N=97)=8.84, p=0.032. A significantly greater proportion of participants who performed expressive writing before the biopsy had fully reepithelialised wounds on day 10 compared to participants who performed neutral writing either before or after wounding, with no other significant differences between groups. Amongst people who wrote expressively after wounding, those who finished writing over the first 6days were significantly more likely to be healed at 14days than those who finished writing later. There were significant differences in positive and negative affect over the healing period between the pre and post expressive writing groups., Conclusions: Expressive writing can improve healing if it is performed prior to wounding. Performing expressive writing after wounding may be able to improve healing depending on the timing of writing and wound assessment. Expressive writing causes affect to worsen followed by subsequent improvement and it is important to consider this in the timing of intervention delivery. Further research with patient groups is required to determine the clinical relevance of these findings., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Higher psychological stress is associated with slower dermal wound healing, but the immunological mechanisms behind this effect are only partially understood. This paper aims to investigate whether immune cells present in the skin prior to wounding can affect subsequent healing in high-stress and low-stress participants. Two studies are presented in which skin biopsies were analysed using immunohistochemistry for numbers of macrophages and Langerhans cells, and immune cell activation (Study 2 only). Immune cells were related to perceived stress levels and subsequent healing. Study 1 included 19 healthy older adults and showed that higher stress was associated with significantly fewer macrophages in the skin. Study 2 included 22 younger adults and showed that higher stress was associated with significantly lower activation of immune cells in the skin. Furthermore, lower activation of immune cells (as measured by human leukocyte antigen (HLA expression)) and fewer Langerhans cells were associated with slower healing. Together these studies show the first preliminary evidence that the number and activation of immune cells in the skin prior to wounding are affected by stress and can impact healing. Larger studies are needed to confirm these effects., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose of Review: Research into the effects of psychological factors on wound healing represents an ideal research model for psychoneuroimmunology, as both the impact on clinically relevant health outcomes and the underlying biological mechanisms can be examined. Mounting interest in this topic from biological scientists, psychologists, and medical specialists has resulted in new findings that are discussed in this review., Recent Findings: Known psychological influences on wound healing include stress as well as coping styles, positive affect, environmental enrichment, and social support. Research has highlighted the roles of oxytocin, vasopressin, epinephrine, cortisol, and leukocyte redistribution in wound healing. Clinical significance has been demonstrated by a growing number of studies in patient populations. Furthermore, pragmatic interventions with clinical samples have demonstrated clear benefits of psychological interventions on wound healing., Summary: Recent studies add to growing evidence that psychology impacts wound repair, and highlight in particular the positive role of social support on modulating the negative effects of stress. The first few studies to demonstrate that psychological interventions can improve healing in clinical populations are exciting developments. New knowledge of psychobiological mechanisms provides opportunities to develop further interventions to improve health outcomes.

Psychological stress has been shown to impair wound healing, but experimental research in surgical patients is lacking. This study investigated whether a brief psychological intervention could reduce stress and improve wound healing in surgical patients. This randomised controlled trial was conducted at a surgical centre. Inclusion criteria were English-speaking patients over 18 years booked to undergo elective laparoscopic cholecystectomy; exclusion criteria were cancellation of surgery, medical complications, and refusal of consent. Seventy five patients were randomised and 15 patients were excluded; 60 patients completed the study (15 male, 45 female). Participants were randomised to receive standard care or standard care plus a 45-min psychological intervention that included relaxation and guided imagery with take-home relaxation CDs for listening to for 3 days before and 7 days after surgery. In both groups ePTFE tubes were inserted during surgery and removed at 7 days after surgery and analysed for hydroxyproline as a measure of collagen deposition and wound healing. Change in perceived stress from before surgery to 7-day follow-up was assessed using questionnaires. Intervention group patients showed a reduction in perceived stress compared with the control group, controlling for age. Patients in the intervention group had higher hydroxyproline deposition in the wound than did control group patients (difference in means 0.35, 95% CI 0.66-0.03; t(43)=2.23, p=0.03). Changes in perceived stress were not associated with hydroxyproline deposition. A brief relaxation intervention prior to surgery can reduce stress and improve the wound healing response in surgical patients. The intervention may have particular clinical application for those at risk of poor healing following surgery., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To provide a critical review of methods used to assess human wound healing in psychological research and related disciplines, in order to guide future research into psychological influences on wound healing., Methods: Acute wound models (skin blister, tape stripping, skin biopsy, oral palate biopsy, expanded polytetrafluoroethylene tubing), surgical wound healing assessment methods (wound drains, wound scoring), and chronic wound assessment techniques (surface area, volumetric measurements, wound composition, and assessment tools/scoring systems) are summarized, including merits, limitations, and recommendations., Results: Several dermal and mucosal tissue acute wound models have been established to assess the effects of psychological stress on the inflammatory, proliferative, and repair phases of wound healing in humans, including material-based models developed to evaluate factors influencing post-surgical recovery. There is a paucity of research published on psychological factors influencing chronic wound healing. There are many assessment techniques available to study the progression of chronic wound healing but many difficulties inherent to long-term clinical studies., Conclusions: Researchers need to consider several design-related issues when conducting studies into the effects of psychological stress on wound healing, including the study aims, type of wound, tissue type, setting, sample characteristics and accessibility, costs, timeframe, and facilities available. Researchers should consider combining multiple wound assessment methods to increase the reliability and validity of results and to further understand mechanisms that link stress and wound healing., (©2010 The British Psychological Society.)

Objective: Laboratory studies have demonstrated that psychological stress is associated with slower healing of small superficial wounds. The application of this finding to the clinical environment has not yet been undertaken. In order to do this, we investigated the relationship between psychological stress and wound repair in patients following routine surgery., Methods: Forty-seven adults with an inguinal hernia were given a standardized questionnaire assessing psychological stress and worry about the operation before undergoing open incision repair. Wound fluid was collected from 36 participants over the first 20-hour postoperative period. Wound healing was assessed by levels of interleukin-1, interleukin-6, and matrix metalloproteinase-9 in the fluid. Other outcome measures included patient self-reports of recovery, as well as cytokine response to lipopolysaccharide stimulation of peripheral blood., Results: Greater preoperative perceived stress significantly predicted lower levels of interleukin-1 in the wound fluid (beta = -0.44, p = 0.03). Greater worry about the operation predicted lower levels of matrix metalloproteinase-9 in the wound fluid (beta = -0.38, p = 0.03) as well as a more painful (beta = 0.51, p = 0.002), poorer (beta = -0.36, p = 0.04), and slower recovery (beta = 0.43, p = 0.01)., Conclusions: Psychological stress impairs the inflammatory response and matrix degradation processes in the wound immediately following surgery. This finding generalizes previous laboratory research to surgical patients and expands the known influence of stress to connective tissue matrix remodelling processes. These results suggest that in clinical practice, interventions to reduce the patient's psychological stress level may improve wound repair and recovery following surgery.