Topical Bixa orellana for Postoperative Wound Healing: A Prospective Randomized Controlled Trial

Abstract

Background:

Numerous ointments may be applied to surgical incisions in the postoperative period to minimize scar formation. There is little evidence assessing their efficacy on wound healing following foot and ankle procedures. This trial was conducted to assess the efficacy of Bixa orellana (Urucu) ointment in the treatment of postoperative elective foot and ankle incisions, compared with conventional postoperative wound care using a control ointment.

Methods:

A prospective, single-center, randomized controlled trial of adults who had undergone elective foot and ankle surgery was performed. Participants were randomized into receiving either a protocol of B orellana ointment application or conventional postoperative wound care with a control ointment. These ointments were applied 2 weeks postoperatively for a 4-week duration. The primary outcome assessed was the Patient and Observer Scar Assessment Scale (POSAS) 6 weeks postoperatively.

Results:

Significant improvements were noted in observer-reported wound vascularity, pigmentation, thickness, relief, pliability, and surface area with the use of Urucu, when compared to the control ointment. Overall, observers reported that scars treated with Urucu cream were found to more closely resemble normal skin with an overall POSAS score of 2.56 compared with 3.33 for the control ointment (P < .01). Lower scores in this instance indicate a more favorable result. Similarly, patients also reported a similar finding with an overall POSAS score of 3.70 for Urucu compared with a control ointment, 4.80 (P = .012). No difference was noted in terms of antibiotic use, delayed wound healing, or return to theatre. Two patients had adverse effects on the application of Urucu ointment in the form of a localized reaction and pruritis that improved with treatment cessation (P = .08). Neither patient required any further intervention.

Conclusion:

Topical Urucu ointment demonstrated promising early improvements in POSAS scores from both patients and observers, particularly in pigmentation and pliability domains, but findings should be interpreted cautiously because of the small sample size and short follow-up.

Level of Evidence:

Level I, randomized controlled trial.

Keywords

wound healing

Introduction

Foot and ankle surgery frequently uses multiple incisions that overlie small mobile joints with little surrounding musculature.¹⁶ Because of its location at the periphery of the appendicular skeleton, this region is inherently less clean and confers an increased risk of infection and poor wound healing.²⁰ There is little literature on interventions that may improve the appearance of surgical scars following foot and ankle surgery.

Several topical treatments claim to improve scar healing with varying degrees of proven effectiveness.^5,13,23 Silver-impregnated hydrogel dressings, for instance, have shown to confer antimicrobial properties while maintaining moist wound environments, resulting in small scar formation.^25,34 Silicon-based dressings have also been found to promote wound healing by reducing inflammation, maintaining moisture content, and reducing water loss.²⁷ It is hypothesized that silicon has a crucial role in collagen synthesis to improve skin elasticity and strength.⁴⁰ There are also emerging topical treatments such as antineoplastic agents, 5-fluorouracil, and methotrexate; however, at present, they require further investigation because of their numerous potential adverse effects.^23,28

Preparations containing B orellana (a plant native to the Central America) have demonstrated wound healing, analgesic, hemostatic, and antioxidant properties derived from various phytochemicals.^7,24,31 Alcohol extracts of B orellana have been shown to inhibit the growth of gram-positive bacteria such as Bacillus subtilis, Staphylococcus aureus, and Enterococcus faecalis. This plant also confers superior antifungal properties when compared to other plant extracts.^3,8,26 B orellana has fewer side effects and lower toxicity compared with synthetic antibiotic preparations and boasts a lack of drug resistance.^3,9

Urucu cream contains B orellana and is licensed primarily in Australia as a cosmetic moisturiser.^8,12 Evidence suggests that compounds containing B orellana have antimicrobial effectiveness; however, there is little evidence in its efficacy on postoperative wounds, let alone those following foot and ankle surgery.^8,33 Thus, this trial aims to evaluate the efficacy of B orellana on postoperative elective foot and ankle wounds, as judged by both patients and clinicians through the Patient and Observer Scar Assessment Scale (POSAS).⁴

Materials and Methods

This study was conducted as a prospective single-masked randomized controlled trial at a private orthopaedic hospital. Following ethics approval, patients undergoing elective foot and ankle surgery procedures performed by a single fellowship-trained foot and ankle surgeon in the years 2019 and 2020 were recruited for inclusion.

Patients were eligible for inclusion if they were aged >16 years; were undergoing foot and ankle surgery resulting in a postoperative wound of at least 5 cm in length; had wounds that were either clean or clean-contaminated; and were able to comply with wound care. Patients were excluded if they were immobilized in a cast or had inadequate access to their wound postoperatively. Patients who defaulted on follow-up appointments, were not compliant with treatment instructions, or moved out of area were also excluded from the study. Patients were permitted to withdraw from the study at any time.

Participants were prospectively randomized to control or treatment groups using permuted block randomization at the initial visit (Figure 1 and Table 1). Figure 1 outlines the study design from patient consent, enrolment, randomization, and POSAS assessment. Table 1 outlines each intervention by their initial review, first review, and final study review/POSAS assessment.

Figure 1.

Study design.

Table 1.

Investigation Plan.

Interventions	Enrolment Visit	Visit 1	Final Study Visit
Informed consent		✓
Inclusion and exclusion criteria	✓
Procedure-intervention or control		✓
POSAS			✓
Adverse event assessment			✓

Abbreviation: POSAS, Patient and Observer Scar Assessment Scale.

Following their operation, all patients underwent standard postoperative wound care, including management of swelling, personal hygiene, limited mobilization, and appropriate footwear. Patients were advised not to massage their postoperative wounds.

All participants were also instructed to apply a layer of homogenous cream to the entire length of the scar at the 2-week postoperative review following the removal of their postoperative dressings. The control group received a compound comprising petroleum jelly, whereas the treatment group applied an ointment made from 7 parts B orellana extract to 93 parts petroleum jelly. Both groups applied the respective creams for a period of 4 weeks following their 2-week review. During this time, no other creams, products, or coverings were permitted. Patients were masked to the treatment arm, whereas observers were not.

The primary outcome assessed was the POSAS at the 6-week postoperative mark. This scale incorporates both patient and observer evaluations. Observers were composed of the primary surgeon, an orthopaedic fellow, and an orthopaedic clinical nurse specialist. Patient domains assessed in the POSAS include wound color, stiffness, thickness, irregularity, pain, and itch as compared to normal skin. Observers undertook appraisals on vascularity, pigmentation, thickness, relief (the extent to which surface irregularities are present), pliability, and surface area. All items are scored out of 10, with a score of 1 assigned to wounds that are likened to normal skin, and 10 to the worst possible outcome. Both patients and observers also record their overall opinion of the scar. Secondary outcomes included the use of antibiotic therapy and other adverse events during the 6-week postoperative period were also reported.⁴ Missing information was sought from the patient’s medical records where necessary in the data collection phase of the study.

Statistical analyses were performed using Statistical Package for Social Sciences (SPSS), version 29. Categorical variables were reported as frequency and percentage. Continuous variables were reported as mean with standard deviation or median with range where appropriate. χ² tests were used for categorical data and Student t test were used for continuous data. A P value of less than .05 was considered significant.³⁷

Results

A total of 89 patients were included in the study. Seventy-five percent of patients recruited were female. The mean age of the cohort was 57 years, with a range of 16-78. Patients receiving topical B orellana were significantly more likely to be hypertensive (P = .003). No other demographic differences were noted between groups (refer to Table 2: baseline characteristics). Table 3 documents the distribution of elective operations by control and intervention groups.

Table 2.

Baseline Characteristics.

Baseline Characteristics	Group A: Control Group	Group B: Urucu Cream	Statistical Test(P Value)^a
Age, y, mean (SD) [n]	58.10 (13.80) [43]	56.92 (14.09) [46]	.345
Gender, female, % [n]	80.95 [42]	71.74 [46]	.311
BMI, mean (SD) [n]	25.85 (4.50) [28]	31.96 (31.68) [30]	.158
Hypertension, % [n]	11.63 [43]	39.13 [46]	.003
Diabetes mellitus, % [n]	5 [43]	7 [46]	.702
Smoking, % [n]	0 [43]	2 [46]	.331

Abbreviation: BMI, body mass index.

Boldface indicates significance (P < .05).

Table 3.

Surgeries of Patients Organized Into the Control and Intervention Groups.

Operation	Group A: Control(n = 42)	Group B: Urucu Cream(n = 37)
Ankle arthroscopy	2	–
Ankle arthroplasty	–	1
Ankle open reduction internal fixation	1	1
Hallux valgus	14	12
Hallux valgus (bilateral)	3	7
Hallux valgus (bilateral) + PIPJ arthrodesis/Weil osteotomy	3	1
Removal of hardware	3	–
First-MTP arthrodesis	13	8
First-MTP arthrodesis (bilateral)	1	3
First-MTP arthroplasty	1	–
First-MTP arthrodesis + Weil osteotomy/PIPJ arthrodesis	–	2
First-MTP cheilectomy and Cartiva implantation	–	1
First-MTP arthrodesis and tibialis anterior reconstruction	1	–
Talar and navicular ostectomies	–	1

Abbreviations: MTP, metatarsophalangeal; PIPJ, proximal interphalangeal joint.

Patients receiving B orellana ointment received significantly superior scores across all clinician domains of the POSAS. This difference, however, was not reflected in the patient domains. Both clinician and patient overall opinions favored wounds that were treated with B orellana (Table 4).

Table 4.

Results of POSAS.^a

Variable	Group A: Control Group,Mean (SD) [n]	Group B: Urucu Cream,Mean (SD) [n]	Statistical Test(P Value)^b
POSAS observer scale
Vascularity	3.18 (1.15) [40]	2.49 (0.63) [45]	.001
Pigmentation	3.20 (1.16) [40]	2.53 (0.82) [45]	.002
Thickness	3.38 (1.15) [40]	2.62 (0.94) [45]	.001
Relief	3.28 (1.11) [40]	2.58 (0.84) [45]	.001
Pliability	3.25 (1.08) [40]	2.56 (0.79) [45]	.001
Surface area	3.43 (1.22) [40]	2.55 (0.79) [45]	.001
Overall	3.33 (1.12) [40]	2.56 (0.76) [45]	.001
POSAS patient scale
Painful	3.12 (1.89) [42]	2.48 (1.82) [46]	.055
Itching	2.51 (2.11) [43]	2.48 (2.17) [46]	.430
Color difference	5.58 (2.56) [43]	5.63 (2.45) [46]	.463
Stiffness difference	5.16 (2.58) [43]	4.33 (2.43) [46]	.060
Thickness difference	5.23 (2.92) [43]	4.39 (2.54) [46]	.076
Irregular	4.91 (2.82) [43]	4.48 (2.62) [46]	.230
Antibiotics	0.00 (0.00) [41]	0.02 (0.15) [42]	.162
Satisfaction	3.92 (0.90) [39]	4.24 (1.05) [45]	.067
Overall opinion	4.80 (2.23) [41]	3.70 (2.12) [40]	.012

Abbreviation: POSAS, Patient and Observer Scar Assessment Scale.

All items on the POSAS were scored on a scale of 1-10, with 10 being the worst possible outcome. A score of 1 was reserved for wounds that resembled normal skin.

Boldface indicates significance (P < .05).

No significant difference was noted between groups in terms of antibiotic administration, delayed wound healing, return to theatre, or noncompliance. Two patients in the intervention group suffered adverse events (a localized reaction and pruritis; P = .08). Both patients discontinued their treatment protocol, and did not require antibiotics or any other intervention.

Discussion

Wound cosmesis is important in obtaining patient satisfaction following surgical procedures, particularly in the elective setting.¹⁵ This study is the first to assess the cosmetic utility of B orellana and finds that application of ointments containing its compounds to postoperative elective foot and ankle incisional wounds was associated with promising early improvements in overall patient and observer POSAS ratings, as well as individual observer domains, when compared to a control substance. These results suggest a potential role for Urucu ointment in optimizing patient-centered cosmetic outcomes, but further investigation is needed to confirm these findings in larger, masked trials with longer follow-up.

Interestingly, despite patients reporting an overall difference in wound quality, they did not notice individual differences in scar characteristics. This may be attributed to several interrelated factors. First, the intervention may have had a heterogenous effect across all domains, resulting in a net-positive change with no significant domain shifts. Furthermore, patients have been found to prioritize holistic scar perception over isolated scar characteristics, causing overall opinions to overshadow domain-level changes.¹ POSAS relies on subjective assessments by both patients and observers, which may have led to scoring variability and bias.²

Unlike the patients, observers reported statistically significant changes in scar characteristic domains. This may have been a result of central tendency bias and the observer’s experienced evaluation of patients’ postoperative wounds.^4,14

Urucu, derived from the seeds of B orellana, has long been used in Amazonian communities for wound care and antimicrobial purposes. This trial represents an early-stage clinical evaluation of Urucu in elective foot and ankle surgery, and interpretation of results should consider study size, masking, and follow-up duration. These findings align with preclinical data suggesting that B orellana possesses antioxidant and anti-inflammatory properties, which may accelerate wound healing by reducing oxidative stress and inflammatory cytokines.^8,12,26 However, the precise molecular mechanisms behind these effects remain unclear and merit further investigation.

Although promising, these results should be interpreted in the context of modern wound management. Prior studies have demonstrated efficacy of treatments such as silicone gel sheeting, corticosteroid creams, and silver-impregnated dressings in improving scar cosmesis and reducing hypertrophic scarring. Future trials comparing Urucu directly with these standard modalities would be valuable in determining its relative effectiveness and cost-benefit.

Two participants who received the intervention ointment reported adverse reactions to the cream in the form of a localized reaction and pruritus. These adverse effects resolved with discontinuation of the cream, with no further intervention required. Regarding the safety of B orellana, documented cases of anaphylaxis and hypersensitivity have only been reported following patient’s ingestion of annatto dye (a derivate of B orellana) used in food manufacturing.³³ Ulbricht et al³³ reported 2 cases of anaphylaxis following ingestion of annatto dye associated with urticaria and angioedema. Given these findings, B orellana has been classified as rarely allergenic.^19,32

Numerous factors underlie successful wound healing and cosmesis. Surgical incisions should be made parallel to Langer’s lines to achieve optimal aesthetic results.²¹ In doing so, the incision is subject to minimal tension, diminishing the risk of scar hypertrophy, infection, necrosis, and wound dehiscence.²⁹ Choice of suture material affects wound healing: absorbable sutures result in lower rates of wound dehiscence, whereas monofilament absorbable sutures may result in lower rates of scar hypertrophy compared with braided absorbable sutures.^12,13 Layered wound closure, with deep dermal sutures to negate skin closure under tension, and everted wound edges also lead to favorable postoperative wounds.^13,14

The use of various dressings and topical agents have been analyzed in wound healing. Silver-impregnant hydrogel sheet dressings have been shown to maintain moist wound environments while conferring antimicrobial properties.³⁴ Miner et al reported that patients treated with silver hydrogel dressings had lower rates of itch, less pain, and smaller scars following foot and ankle surgery, when compared to a control petroleum-based dressing.⁴¹ The use of creams incorporating hyaluronic acid, or ATP-vesicles, have also garnered interest but remain without consensus because of a lack of high-quality studies in humans.^29,39

Silicon-based dressings and agents have also been found to promote wound healing by reducing inflammation, maintaining moisture content, and reducing water loss. They do, however, need to be applied for over 6-12 months to achieve an optimal result.²⁷ It is hypothesised that silicon is crucial for optimum collagen synthesis while also activating hydroxylating enzymes, which improves skin elasticity and strength.⁴⁰ Hu et al¹⁰ reported a novel multifunctional silicon-carbon nanohybrid (SiCNs) which has high bacterial inhibition activity (≈82.9% killing rate toward S aureus) and heightened hemostatic effects, shortening bleeding time from approximately 60 to 15 seconds. Compared with conventional dressings, silicon-based preparations were also found to have faster epithelialization, accelerating wound healing by 20% to 40%.¹⁸

Multiple studies have established the antimicrobial efficacy of B orellana. Ethanolic extracts of this compound are particularly effective against gram-negative bacteria, although they also possess activity against fungi and gram-positive organisms.^11,12,21,22 Studies have revealed that apart from staphylococcal species, pathogens in surgical site infections following elective foot and ankle surgery often include gram-negative species; therefore, the wide range of B orellana’s bioavailability is of value in this setting.^36,39 It is important to note that the rate of elective foot and ankle surgical site infections is up to 10 times greater than that seen in elective knee and hip arthroplasty; thus, any intervention that may reduce it may be of great clinical interest.^36,39

The POSAS assessment was used because of its reliability, widespread use, and ability to provide feedback from all invested stakeholders.^4,13 This scale has been revised twice since the onset of this study, with a greater depth of analysis from the patient perspective. Unfortunately, these variations could not be incorporated into this analysis; however, they would be beneficial in future studies.⁴ It is worth noting that the minimal important change (MIC) values of the patient POSAS ranged from −0.59 to −0.29 between 3 and 6 months and from −0.75 to −0.38 between the 6- and 12-month follow-ups.¹⁷ This suggests that patients consider minor differences (less than 0.75 on the 1-10 scale) in POSAS as clinically important wound quality changes. Unfortunately, this highlights a limitation of this study, and future projects should ensure that the POSAS is repeated over a prolonged period to ensure a more accurate evaluation of final scar quality.³⁰

Other limitations of this study include measurement bias because of the single-masked nature of the trial as observers were not masked to the patient’s treatment allocation.¹³ Future studies would benefit from masking of the patients and observers to the treatment modality received.³⁸ Only a 7% concentration of B orellana was used, and there is currently no standardization of Urucu ointment formulation or dose-response data.³³

Future studies would also benefit from a photographic scar assessment by other members of the investigating team. This was undertaken by Khoo et al,¹³ who reported no significant difference between 2 independent assessors in scoring the parameters of scars on a series of photographic images using a visual analog scale in evaluating the effects of topical tocotrienol (P = .711).

A total of 89 patients were included in this study, with a mean age of 57 years and a range of 16-78 years. Seventy-five percent of patients recruited in this study were female. In both the control and intervention groups, a statistically significant proportion of patients had hypertension (P = .003). There were no other statistically significant findings in the baseline characteristics of the 2 groups in terms of age, gender, body mass index, diabetes mellitus, and smoking. Nonetheless, it is understood that patients with diabetes, hypertension, obesity, tobacco usage, have poorer wound healing outcomes that could be confounding factors in this study.⁶ Furthermore, male patients and patients 60 years or older have a higher likelihood of postoperative wound complications.³⁵

This study indicates that topical administration of B orellana shows promising, early potential in improving the cosmesis of postoperative wounds in foot and ankle surgery. The study’s sample size was constrained by feasibility, and a formal power calculation was not performed. Future trials will benefit from the incorporation of doubling masking, longer follow-up periods, use of an updated version of POSAS, photographic assessment, and an improved baseline group balance.

Conclusion

The use of Urucu ointment demonstrated promising early results for scar appearance in elective foot and ankle surgery, as assessed by patients and clinicians using the POSAS. However, these findings should be interpreted with caution because of the small sample size, lack of masking, and short follow-up period.

Supplemental Material

sj-pdf-1-fao-10.1177_24730114251345821 – Supplemental material for Topical Bixa orellana for Postoperative Wound Healing: A Prospective Randomized Controlled Trial

Supplemental material, sj-pdf-1-fao-10.1177_24730114251345821 for Topical Bixa orellana for Postoperative Wound Healing: A Prospective Randomized Controlled Trial by Joshua T. Chew, Joshua J. Xu, Thomas A. J. Goff, Karen A. Fogarty, Michael J. Symes, Brahman S. Sivakumar and Andrew P. Wines in Foot & Ankle Orthopaedics

Footnotes

Ethical Approval

Ethical approval for this study was obtained from the St Vincent’s Hospital Research Office (Human Research Ethics Application AU/1/B2E8313). (SVH File Number: 18/228).

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Disclosure forms for all authors are available online.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

Joshua T. Chew, BEng(Hons), MD,

Thomas A. J. Goff, MBCHb, FRCS,

Michael J. Symes, BPhysio(Hons), MBBS(Hons), MPH, FRACS, FAOrthA,

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