research
Hard-to-heal wounds: a randomised
trial of an oral proline-containing
supplement to aid repair
Objective: We evaluated the effects of a specialised oral nutritional
supplement (ONS) containing arginine and proline, with high
vitamin A, C and E, zinc and selenium content, on the repair of
hard-to-heal wounds.
Method: Patients with hard-to-heal wounds were evaluated at five
timepoints (S0–S4) over four consecutive weeks. At S0 patients were
randomised to the specialised ONS (n=15; 25 wounds) or control
(n=15; 25 wounds) groups. Posology was 200ml twice daily over the
research period. Wound surface area and perimeter were monitored.
In addition to the metric data, it was also possible to calculate the
rate of wound contraction and the linear growth of the wound edges,
looking for wound-healing predictive factors.
Results: A total of 30 patients took part in the study. Mean age was
65 years and 50% of patients had diabetes. Of the total evaluated
wounds, 78% were <50cm2, 14% were 50–150cm2 and 8% were
>250cm2. In 96% of cases, the wounds were in the lower limbs. A
statistically significant reduction (p=0.004) in surface area of the
chronic wound ● diabetes ● dressings ● hard-to-heal wound ● oral nutritional supplement
W
ound healing is a multicellular
physiological process1 of programmed
and reproducible cooperation of the
cells involved.2 It is one of the most
complex biological processes that
occurs during human life.3 Wounds are the result of
tissue disruption with loss of normal anatomical structure
and consecutive loss of normal tissue function.4 The
wound healing process generates resurfacing and
reconstitution of tissues, as well as restoration of the
tensile strength of the injured tissue.5 It starts within
seconds of the injury with haemostasis, followed by the
phases of inflammation, proliferation and tissue
remodelling, for restoring the tissue integrity and barrier
function of the skin.6 From the metabolic standpoint, all
of these phases require sufficient energy and protein
substrate to ensure that wound healing is successful.7
Adriano A Mehl,1 MD, MSc, PhD, Leading Researcher*; Adérson OMC Damião,2 MD,
MSc, PhD, Researcher; Sâmela DDO Viana,3 Nutritionist Specialising in Clinical and
Hospital Nutrition; Camila P Andretta,4 Nutritionist Specialising in Clinical Nutrition
Corresponding author email: adrianomehl@gmail.com; adrianomehl@hotmail.com
1 Universidade Tecnológica Federal do Paraná, Brazil. 2 Universidade de São Paulo,
Brazil. 3 Grupo de Apoio de Nutrição Enteral e Parenteral, Brazil. 4 Faculdade
Evangélica do Paraná, Brazil.
26
wounds due to the specialised ONS, with a performance peak
between S1 and S2, was observed. This specialised ONS did not
induce changes in blood pressure, blood glucose level or renal
function. A mean weekly wound edge growth of 1.85mm in patients
with diabetes and 3.0mm in those without diabetes was observed.
These results were 2.9 and 4.6 times, respectively, higher than
expected, according to the literature.
Conclusion: Specialised ONS can be a therapeutic option for hard-
to-heal wounds.
Declaration of interest: AAM received a research grant as the
principal investigator and an honorarium as a speaker for Nestlé
Health Science, Brazil, patent holder of the products Nutren Senior
(200ml) and Novasource Proline (200ml). SDDOV is a member of the
Scientific Affairs Department of Nestlé Health Science and AOMCD
was a member of the Scientific Affairs Department of Nestlé Health
Science, Brazil. CPA works as a nutritionist for Le Farma (Nestlé
Distributor) in Curitiba, Paraná, Brazil.
● proline ● ulcers ● wound healing
Hard-to-heal wounds are defined as those that fail to
proceed through these phases in an orderly and timely
manner, not progressing within a period of 3–4 weeks.8–10
They include lower extremity ulcers (for example,
venous, arterial or mixed ulcers), pressure ulcers and
neuropathic foot/leg ulcers (for example, in diabetes,
leprosy and alcoholism).9,11,12
Hard-to-heal wounds represent a silent epidemic.11
They affect a large fraction of the world’s population
and pose a growing threat to public health, with a
substantial negative economic impact.10–14
In addition, there are repercussions from the personal,
psychological and social standpoints, and hard-to-heal
wounds are among the leading causes of work absence,
with high relapse rates.13,14 Hard-to-heal wounds affect
5% of the adult population in Western countries.14 In
the US, hard-to-heal wounds affect approximately six
million individuals at an annual cost of $25 billion
USD.13 In the Scandinavian countries, the associated
costs account for 2–4% of total healthcare expenses.13
© 2021 MA Healthcare ltd
Damaged tissue needs several nutrients to be repaired.
Nutritional intake plays an essential role in this
process.15 An adequate intake of macronutrients
(carbohydrate, protein and fat) is recommended as
much as an intake of micronutrients, such as zinc,
JOURNAL OF WOUND CARE VOL 30, NO 1, JANUARY 2021
Downloaded from magonlinelibrary.com by 147.161.128.113 on February 20, 2024.
 research

selenium and vitamins (A, C and E).16 Certain amino
acids, such as arginine, play an important role in the
healing process.16 Arginine participates in protein
synthesis in general, stimulates cell signalling and
proliferation, and is also a precursor to glutamine and
proline.17–19 Growing evidence shows that proline is a
key regulator of multiple biochemical and physiological
processes of cells.20 Proline is a signalling molecule, a
sensor of cellular energy status, and a source of
pyrroline-5-carboxylate (P5C) and the superoxide
anion, participating in redox reactions in humans and
animals.20 Proline and its metabolite (hydroxyproline)
constitute about one-third of collagen-forming amino
acids. Collagen comprises approximately 30% of the
body’s proteins and is the main extracellular component
of connective tissues (for example, skin, tendon and
cartilage).20,21
Although the importance of nutrition for the wound
healing process has been established in the literature,15–19
few clinical trials16–18 have reported the effectiveness of
oral nutritional supplements (ONS) specialised in repair
of hard-to-heal wounds.
This study involved the prospective, randomised,
controlled assessment of the effects of a nutritional
supplement specialised in this group of hard-to-heal
wounds. The amino acids proline and arginine, with
high levels of vitamins A, C and E, zinc and selenium,
are the differential elements of this supplement.
Methods
Ethical approval
This study started after approval by the Ethics
Committee for Research Involving Human Beings (CEP)
of the Universidade Tecnológica Federal do Paraná
(UTFPR), Brazil (Certificate of Presentation for Ethical
Consideration: 62393316.3.0000.5547; Certificate:
123435/2016).
Patients
The inclusion and exclusion criteria for selection of
patients in this study are described in Table 1. All
included individuals received a copy of the Free and
Informed Consent Form and signed it after being guided
and informed on the procedures to be adopted during
the study. All patients provided authorisation for this
study, including use of images (for the recording of
metric data). All of these supporting documents are
available from the investigators for consultation at
any time.
The selected patients underwent an initial assessment
and were monitored at an outpatient wound and
diabetic foot ulcer care centre in Curitiba, Paraná, Brazil.
They were monitored once a week for four consecutive
weeks. This totalled five timepoints (S0–S4) that
© 2021 MA Healthcare ltd
The primary objective was to calculate the percentage
rate of wound contraction throughout the four-week
period. Secondary objectives were healing rate
(millimetres per week of growth at wound edges),
nutritional and laboratory parameters.
Patient groups and ONS employed
At initial assessment (S0) patients were randomised for
the intervention group with the specialised ONS under
test (Novasource Proline, Nestlé, Brazil) or for the
control group (Nutren Senior Nestlé, Brazil) (Table 2).
The ONS to be studied contained the amino acids
proline and arginine, with high levels of vitamins A, C
and E and minerals zinc and selenium. Both the ONS
and control were high-protein formulas provided in
ready-to-drink forms (Tetra Slim Packaging, 200ml). The
dosage for the daily intake was 200ml, twice daily,
during the study stage (30 days).
Both on the first (S0) and last (S4) days of evaluation,
patients were assessed by one of the research dietitians.
The Subjective Global Assessment (SGA) was used in
patients under 60 years of age, 22 and the Mini
Nutritional Assessment (MNA) was used in patients over
60 years of age.23,24
Also, at these two timepoints, the patients had their
blood collected for laboratory tests according to the
research protocol. The samples collected were tested for
complete blood count, albumin and prealbumin, as
useful markers of the nutritional status,25 and glycaemia
and creatinine for glycaemic and renal function control,
respectively.
Topical therapy
Coverage by dressings (topical therapy) used to combat
biofilm was maintained throughout the study. Dressings
containing silver (alginate, hydrofibre, foam),
polyhexamethylene biguanide (solution, gel or
impregnated gauze) or cadexomer iodine (paste) were
Table 1. Inclusion and exclusion criteria adopted for the study
Inclusion criteria Exclusion criteria
Male or female patients over 18 years Severely malnourished patients
of age (weight loss of 40% or more, or
malnourished with oedema, regardless
of weight)
Patients with hard-to-heal wounds: Patients with thyroid disease without
venous, arterial or mixed ulcers, proper monitoring and debilitating
pressure ulcers and neuropathic foot/ chronic disease (cerebral, cardiac,
leg ulcers (evolution of wounds for renal or pulmonary)
>3–4 weeks8,9)
Patients with or without diabetes type 1 Patients receiving chemotherapy or
or type 2 undergoing treatment and radiotherapy, corticosteroid pulse or
medical follow-up use of anti-inflammatory drugs

provided information on and enabled assessment of
both the clinical conditions and the wounds. All the
patients had their wounds documented by
measurements and photographs, according to a
sequence of wound bed preparation and dressings.
Patients without arterial hypertension or
with arterial hypertension undergoing
treatment and medical follow-up
Patients with or without spinal cord
injury
Subjects with tobacco habits, alcohol
intake and drug users
Patients with hard-to-heal wounds with
exposure of metal plate, screw or wire

JOURNAL OF WOUND CARE VOL 30, NO 1, JANUARY 2021 27

Downloaded from magonlinelibrary.com by 147.161.128.113 on February 20, 2024.
 research
Table 2. Comparison of composition and laboratory assessment
of the control versus the oral nutritional supplement (ONS)
Control ONS (200ml) Specialised ONS (200 ml)
Kcal/unit 193 274
Proteins (g) 16 20
Vitamin C (mg) 16 250
Vitamin A (µg RE) 200 200
Vitamin E (mg α-TE) 4.8 36
Zinc (mg) 4.0 11
Selenium (µg) 24 72
Arginine (mg) - 3000
Proline (mg) - 2000
RE—retinol equivalent; TE—alpha-tocopherol equivalent
used to combat biofilm. Biofilms are complex
microbiological ecosystems that cover the surface of
wounds, compromising healing.26 Since wounds were
hard-to-heal, standardised treatment for biofilm was
chosen. The diagnosis and treatment of hard-to-heal
wounds cannot neglect biofilm.27 Hard-to-heal wounds
are an environment with good living conditions for
many microorganisms, and biofilm appears in 60–90%
of hard-to-heal wound biopsy samples.10,26,28,29
Metrics and photographic monitoring
The leading research physician measured and
photographed all the wounds on a weekly basis, always
with the same photography equipment. A sterile ruler,
a Vernier Calliper 125 MEB-6/150 and software for
image processing of surface area and perimeter
calculations were used for collecting and recording
wound measurement data.
Wound contraction percentage rate
and linear growth calculation
In addition to metric data, it was also possible to
calculate contraction percentage rate and linear growth
of wound edges. Wound contraction percentage rate
can be used to track an ulcer over time.10 Weekly
comparisons of wound area reduction rates can be
converted into wound healing trajectory curves,
particularly in the first 2–4 weeks of treatment. 10
Wounds showing an area reduction rate of 10–15% per
week predict healing;10,30 those showing 30–50% area
reduction in the first 2–4 weeks have high healing
potential.10,31,32
Calculation of contraction percentage rate
(Equation 1) is a significant prognostic factor and has a
predictive value in wound healing when applied in the
first 2–4 weeks of the recommended therapies.10
%Co = (S0–S1)/S0 × 100 (1)
where: %Co: wound contraction % or area variation
rate; S0: area of wound in Week 0 (baseline); S1: area of
wound in Week 1.
The linear growth calculation using Gilman’s equation
28
(Equation 2) requires monitoring of the wound edge
margin progress (centripetally). This is a useful measure
for establishing the healing rates10 as it takes into
account both the initial and the final wound perimeter
in a given period. It has a comparative effect on the
healing progress (or not), as it relates area, perimeter and
time of evolution, regardless of the initial area.
D=ΔA/(P1+P2+...Pn/n) (2)
where: D: linear growth; ΔA: area variation in the
period; P1+P2+...Pn: sum of the perimeter values; n:
number of weeks.
Hard-to-heal wounds show a weekly healing rate of
around 0.49–0.65mm in the first four weeks of therapy
with adequate wound healing stimulation.33 This
information suggests that there can be a relatively
uniform healing rate, regardless of aetiology. Therefore,
a period of up to four weeks is expected to be sufficient
to establish a trend of evolution in the wound healing
process of this study.
Statistical analysis description
The data obtained in this study were described as
means, standard deviations (SD) and standard errors
(quantitative variables) or frequencies and percentages
(categorical variables). The comparison of therapies and
groups took into account the analysis of variance
(ANOVA) model with two sources of variation.
The comparison of two evaluation moments with
regard to quantitative variables was carried out with
Student’s t-test for paired samples. With regard to
wound-related variables, in view of the possibility of
patients with more than one ulcer, each patient was
considered as a cluster. For the comparisons of interest,
the ratio estimation model with quantitative variables
and the ratio estimation model with cluster were used
for dichotomic variables. P-values <0.05 indicated
statistical significance. Data were analysed with the
statistical software Stata/SE v.14.1 (StataCorp LP, US).
Results
Of the 34 invited patients, 30 met the criteria for
inclusion and were monitored: 14 males and 16 females
with 50 ulcers altogether (1.67 ulcers per patient). The
mean age was 64.7 years (range 39–89 years).
Of the 30 patients, 15 had type 2 diabetes, and nine
patients (60%) of these were also hypertensive. Of the
non-diabetic patient group, six (40%) patients were
hypertensive.
Hard-to-heal wounds were classified according to
their origin as nonsurgical and surgical. Nonsurgical
hard-to-heal wounds, such as chronic lower extremity
vascular ulcers, pressure ulcer, neuropathic foot ulcers
© 2021 MA Healthcare ltd
(diabetic) and neuropathic ulcers (leprosy sequelae)
represented 92% of the total examined ulcers. Others
were hard-to-heal wounds caused by delayed healing
after debridement procedures and amputations.
Table 3 shows the number of patients and percentages
JOURNAL OF WOUND CARE VOL 30, NO 1, JANUARY 2021
Downloaded from magonlinelibrary.com by 147.161.128.113 on February 20, 2024.
 research

according to number of ulcers for each group defined Table 3. Distribution of groups of patients, number of ulcers and
for treatment. diet treatments
Of the total examined ulcers, 78% measured up to Number of ulcers Group (treatment)
50cm², 14% measured up to 150cm² and 8% were larger Specialised ONS Control ONS
than 250cm² in surface area. In 96% of cases, ulcers
n % n %
were located in lower extremities, and there was a
1 8 53.3 8 53.3
female patient with a clinical history of a venous leg
ulcer for 30 years. 2 5 33.3 5 33.3
Each defined group and each assessment timepoint 3 1 6.7 1 6.7
were compared (S0–S1, S1–S2, S2–S3, S3–S4 and S0–S4). 4 1 6.7 1 6.7
The average area reduction rate of the two treatment
Total 15 100 15 100
groups was also tested (null hypothesis against the
ONS—oral nutritional supplement
alternative hypothesis). The p-values of statistical tests
are presented in Table 4.
Fig 1 presents values according to groups and Fig 1. Weekly reduction (%) of wound area. Monitoring specialised oral
nutritional supplement (ONS) and control ONS
treatments. In this study, we observed a statistically
significant reduction of wound surface area with the use
of the specialised ONS, and peak performance between 30
% weekly reduction of wound area
S1 and S2. The literature indicates that wounds with a 25
percentage area reduction of 30–50% in the first 2–4
weeks have high healing potential.10,30–32,34 20
The use of the specialised ONS over the four-week 15
period showed an average weekly wound edge growth
of 1.85mm per week in patients with diabetes and 10
3.0mm per week in those without, being 2.9 and 5
4.6 times higher than expected according to the
literature, respectively.33 The highest value found in the 0
specialised ONS group in patients with diabetes was -5
7.2mm per week, and 11.0mm per week in patients S0–S1 S1–S2 S2–S3 S3–S4
without diabetes.  Specialised ONS  Control ONS
With regard to clinical and laboratory parameters
assessed during the study, there were no significant
differences in blood pressure, glycaemia, renal function attention must be given to factors such as adequate
(creatinine), albumin and prealbumin levels. protein energy supply.17,35 In spite of this, little is
Although wound healing is a complex process, known about the exact mechanism of some nutrients
collagen synthesis is required for it to take place. This in the healing process, as well as their direct action on
synthesis depends on proline and lysine hydroxylation, the healing process, supplementation dosage and
the presence of cofactors such as vitamins A, E and C, optimal period of use.
iron, zinc and selenium, and the oxygenation of Table 5 shows general information and functions of
cells.19,20 For this process to occur ideally, special the main compounds in the specialised ONS under test.

Table 4. P-values of statistical tests

Group Assessment n Surface area reduction percentage p-value**

Mean Standard
deviation*
Control ONS S0–S1 15 11.3 20.4 0.051
S1–S2 15 –1.8 40.0 0.867
S2–S3 15 11.2 21.2 0.059
S3–S4 15 26.8 33.6 0.008
S0–S4 15 34.0 32.1 0.001
Specialised ONS S0–S1 15 4.2 22.6 0.487
S1–S2 15 15.0 17.0 0.004
© 2021 MA Healthcare ltd

S2–S3 15 8.8 19.6 0.104

S3–S4 15 3.3 33.2 0.704
S0–S4 15 28.4 32.0 0.004
*Standard deviation of differences between the two timepoints analysed; ** Student's t-test, p<0.05; ONS—oral nutritional supplement; S0–S4—weekly timepoints

JOURNAL OF WOUND CARE VOL 30, NO 1, JANUARY 2021 29

Downloaded from magonlinelibrary.com by 147.161.128.113 on February 20, 2024.
 research
Table 5. General information on the components of the specialised
oral nutritional supplement (ONS) formula and main functions
Components Functions and general information
Arginine An essential amino acid that plays an important role in protein
synthesis, and in cell signalling and proliferation. It positively
influences wound healing, since it is capable of producing
microvascular changes and tissue perfusion, and it contributes
to the production of collagen
Proline Plays an important role in protein synthesis and structure,
antioxidation reactions and immune responses. Proline and its
metabolite (hydroxyproline) constitute one-third of the amino
acids in the collagen proteins, which comprise approximately
30% of body proteins
Vitamin A Plays a key role in immune function, with actions described in
maintenance of mucosal integrity, differentiation, growth and
function of neutrophils, monocytes, Langerhans cells and T and
B lymphocytes, modulation of phagocytic cell response,
phagocytosis stimulus, mucin expression, keratin and
cytokines. During inflammatory processes, vitamin A can be
significantly reduced
Vitamin C Necessary for hydroxylation of proline and Iysine in collagen
synthesis, where it stabilises the triple helix structure of
collagen. It also contributes to optimal immune response and
migration to the wound tissue of monocytes that become
macrophages during the inflammatory phase of wound healing
Vitamin E A membrane antioxidant, it protects against oxidation damage
and contributes to photoprotection (in combination with
vitamin C)
Zinc Essential for DNA synthesis, cell division and protein synthesis.
Required by all proliferating cells, including inflammatory cells,
epithelial cells and fibroblasts, thus playing an important role in
the immune function. It is also indicated as a cofactor for the
formation of collagen
Selenium Has antioxidant properties and provides consequent protection
against peroxidation. It plays an essential role in regulating
migration, proliferation, differentiation, activation and optimal
function of immune cells, thereby influencing innate (B-cell) and
acquired (T-cell) immunity. The healing mechanism and its
direct role in it is not yet very clear
The nutritional treatment goals to be achieved in a
wound patient are:
● Provide adequate calorie intake
● Prevent protein-calorie undernutrition
● Promote wound healing.
References
1 Baum CL, Arpey CJ. Normal cutaneous wound healing: clinical
correlation with cellular and molecular events. Dermatol Surg 2005;
31(6):674–686. https://doi.org/10.1111/j.1524-4725.2005.31612
2 Gonzalez ACO, Costa TF, Andrade, ZA, Medrado ARAP. Wound healing:
a literature review. An Bras Dermatol 2016; 91(5):614–620. https://doi.
org/10.1590/abd1806-4841.20164741
3 Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and
regeneration. Nature 2008; 453:314–321. https://doi.org/10.1038/
nature07039
4 Reinke JM, Sorg H. Wound repair and regeneration. Eur Surg Res 2012;
49(1):35–43. https://doi.org/10.1159/000339613
5 Arya AK, TripathI K, Das P. Promising role of ANGPTL4 gene in diabetic
wound healing. Int J Low Extrem Wounds 2014; 13(1): 58–63. https://doi.
30
Awareness among health professionals of the
important role that nutrition plays in overall wellness
and disease treatment is very low and should be
encouraged.36
An early and timely nutritional intervention will help
reverse the negative consequences of malnutrition.25,37–40
The use of a specialised ONS aimed at healing should be
considered from the initial assessment as a tool of early
intervention in wound treatment.
An adequate nutritional status can be measured not
only through wound evolution and resolution but also
through absence of infections and other complications
during the healing process.7
The specialised ONS tested achieved the nutritional
goals and provided this study with results that
corroborate the findings in the literature.
Limitations
In this study we followed the healing behaviour of
hard-to-heal wounds over a short period (four weeks).
Patients with various types of comorbidities and
different sizes of wounds were recruited, which may
have limited the conclusions that can be drawn. The
calculation of a predictive factor of healing should be
encouraged in wound research. The findings of this
study are promising but need to be replicated in a
larger study.
Conclusion
This study demonstrated, despite the short follow-up
period, that within two weeks, stimulation of the repair
process of hard-to-heal wounds is possible with
specialised ONS.
The specialised ONS emerged as a new source of easy-
to-use protein, enriched with elements such as proline
and arginine, vitamins A, E and C, zinc and selenium,
directly connected to the wound healing process, both
in individuals with and without diabetes.
The use of specialised ONS, aimed at hard-to-heal
wound repair specifically, should be considered from
the initial patient assessment as an important tool in
wound treatment. JWC
Acknowledgments: All authors read and approved the final version
of the manuscript.
org/10.1177/1534734614520704
6 Sgonc R, Gruber J. Age-related aspects of cutaneous wound healing: a
mini-review. Gerontology 2013; 59:159–164. https://doi.
org/10.1159/000342344
7 Albaugh VL, Mukherjee K, Barbul A. Proline precursors and collagen
synthesis: biochemical challenges of nutrient supplementation and wound
healing. J Nutr 2017; 147(11):2011–2017. https://doi.org/10.3945/
© 2021 MA Healthcare ltd
jn.117.256404
8 Hermans MH. Wounds and ulcers: back to the old nomenclature.
Wounds 2010; 22(11):289–293
9 Martinengo L, Olsson M, Bajpai R et al. Prevalence of chronic wounds in
the general population: systematic review and meta-analysis of
observational studies. Ann Epidemiol 2019; 29:8–15. https://doi.
JOURNAL OF WOUND CARE VOL 30, NO 1, JANUARY 2021
Downloaded from magonlinelibrary.com by 147.161.128.113 on February 20, 2024.

org/10.1016/j.annepidem.2018.10.005
10 Mehl AA, Schneider Jr B, Schneider FK, Carvalho BHK. Measurement
of wound area for early analysis of the scar predictive factor.
Rev Latino-Am Enfermagem 2020; 28:e3299. https://doi.
org/10.1590/1518-8345.3708.3299
11 Järbrink K, Ni G, Sönnergren H et al. Prevalence and incidence of
chronic wounds and related complications: a protocol for a systematic
review. Syst Rev 2016; 5(1):152. https://doi.org/10.1186/
s13643-016-0329-y
12 Zhao R, Liang H, Clarke E et al. Inflammation in chronic wounds. Int J
Mol Sci 2016; 17(12):2085. https://doi.org/10.3390/ijms17122085
13 Sen CK, Gordillo GM, Roy S et al. Human skin wounds: a major and
snowballing threat to public health and the economy. Wound Repair Regen
2009; 17(6):763–771. https://doi.org/10.1111/j.1524-475X.2009.00543.x
14 Oliveira AC, Rocha DM, Bezerra SMG et al. Quality of life of people
with chronic wounds [in Portuguese]. Acta Paulista de Enfermagem 2019;
32(2):194–201. https://doi.org/10.1590/1982-0194201900027
15 Guo S, DiPietro LA. Factors affecting wound healing. J Dent Res 2010;
89(3): 219–229. https://doi.org/10.1177/0022034509359125
16 National Pressure Ulcer Advisory Panel, European Pressure Ulcer
Advisory Panel and Pan Pacific Pressure Injury Alliance. Prevention and
treatment of pressure ulcers: Quick reference guide. Emily Haesler (Ed.).
Cambridge Media: Osborne Park, Western Australia, 2014. https://www.
epuap.org/wp-content/uploads/2016/10/quick-reference-guide-digital-
npuap-epuap-pppia-jan2016.pdf (accessed 16 December 2020)
17 Wild T, Rahbarnia A, Kellner M et al. Basics in nutrition and wound
healing. Nutrition 2010; 26(9):862–866. https://doi.org/10.1016/j.
nut.2010.05.008
18 Posthauer ME, Dorner B, Collins N. Nutrition: a critical component of
wound healing. Adv Skin Wound Care 2010; 23(12):560–572. https://doi.
org/10.1097/01.ASW.0000391185.81963.e5
19 Doley J. Nutrition management of pressure ulcers. Nutr Clin Pract
2010; 25(1):50-60. https://doi.org/10.1177/0884533609359294
20 Wu G, Bazer FW, Burghardt RC et al. Proline and hydroxyproline
metabolism: implications for animal and human nutrition. Amino Acids
2011; 40:1053–1063. https://doi.org/10.1007/s00726-010-0715-z
21 Ponrasu T, Jamuna S, Mathew A et al. Efficacy of L-proline
administration on the early responses during cutaneous wound healing in
rats. Amino Acids 2013; 45:179–189. https://doi.org/10.1007/
s00726-013-1486-0
22 Detsky AS, McLaughlin JR, Baker JP et al. What is subjective global
assessment of nutritional status? JPEN J Parenter Enteral Nutr 1987;
11(1):8–13. https://doi.org/10.1177/014860718701100108
23 Kaiser MJ, Bauer JM, Uter W et al. World-wide data on malnutrition in
the elderly according to the Mini Nutritional Assessment® (MNA): Insights
from an international pooled database. Clin Nutr Supp 2009; 4(2):113–114.
https://doi.org/10.1016/S1744-1161(09)70260-1
24 Machado RSP, Coelho MASC, Veras RP. Validity of the Portuguese
version of the mini nutritional assessment in Brazilian elderly. BMC Geriatr
2015; 15:132. https://doi.org/10.1186/s12877-015-0129-6
25 Molnar JA, Underdown MJ, Clark WA. Nutrition and chronic wounds.
Adv Wound Care 2014; 3(11):663–681. https://doi.org/10.1089/
wound.2014.0530
26 Kucisec-Tepes N. The role of antiseptics and strategy of biofilm
removal in chronic wound [article in Croatian]. Acta Med Croatica 2016;
70(1):33–42. https://www.ncbi.nlm.nih.gov/pubmed/27220188 (accessed
16 December 2020)
JWC available at
Register for free and take advantage
of these great benefits and features:
 Save JWC articles for quick access
 Save your searches: great if you frequently search for
the same criteria
© 2021 MA Healthcare ltd
 Get citation alerts to track citations to specific articles
www.magonlinelibrary.com/r/jowc
JOURNAL OF WOUND CARE VOL 30, NO 1, JANUARY 2021
research
Reflective questions
● How can hard-to-heal wounds put patients at risk?
● What are the contributions of the amino acids arginine and proline to the
wound healing process?
● What are the goals of nutritional therapy to be achieved in a patient with a
hard-to-heal wound?
● What method do you use to calculate the wound healing predictive factor?
27 Hurlow J, Blanz E, Gaddy JA. Clinical investigation of biofilm in
non-healing wounds by high resolution microscopy techniques. J Wound
Care 2016; 25(Sup9):S11–S22, https://doi.org/10.12968/jowc.2016.25.
Sup9.S11
28 Omar A, Wright JB, Schultz G et al. Microbial biofilms and chronic
wounds. Microorganisms 2017; 5(1):9. https://doi.org/10.3390/
microorganisms5010009
29 Ead JK, Snyder RJ, Wise J et al. Is PASH syndrome a biofilm disease?
A case series and review of the literature. Wounds 2018; 30(8):216–223.
https://www.ncbi.nlm.nih.gov/pubmed/30212364 (accessed 16 December
2020)
30 Hingorani A, LaMuraglia GM, Henke P et al. The management of
diabetic foot: a clinical practice guideline by the Society for Vascular
Surgery in collaboration with the American Podiatric Medical Association
and the Society for Vascular Medicine. J Vasc Surg 2016; 63(2):3S–21S.
https://doi.org/10.1016/j.jvs.2015.10.003
31 Khoo R, Jansen S. The evolving field of wound measurement
techniques: a literature review. Wounds 2016; 28(6):175–181. https://www.
ncbi.nlm.nih.gov/pubmed/27377609 (accessed 16 December 2020)
32 Foltynski P. Ways to increase precision and accuracy of wound area
measurement using smart devices: advanced app Planimator. PLoS ONE
2018; 13(3):e0192485. https://doi.org/10.1371/journal.pone.0192485
33 Margolis DJ, Gross EA, Wood CR, Lazarus GS. Planimetric rate of
healing in venous ulcers of the leg treated with pressure bandage and
hydrocolloid dressing. J Am Acad Dermatol 1993; 28(3):418–421. https://
doi.org/10.1016/0190-9622(93)70061-w
34 Dastjerdi HM, Töpfer D, Rupitsch SJ, Maier A. Measuring surface area
of skin lesions with 2D and 3D algorithms. Int J Biomed Imaging 2019;
2019:4035148. https://doi.org/10.1155/2019/4035148
35 Ord H. Nutritional support for patients with infected wounds. Br J
Nursing 2007; 16:1346–1352. https://doi.org/10.12968/
bjon.2007.16.21.27724
36 Citty SW, Cowan LJ, Wingfield Z, Stechmiller J. Optimizing nutrition
care for pressure injuries in hospitalized patients. Adv Wound Care 2019;
8(7):309–322. https://doi.org/10.1089/wound.2018.0925
37 Skipper A. Challenges in nutrition, pressure ulcers, and wound healing.
Nutr Clin Pract 2010; 25(1):13–15. https://doi.
org/10.1177/0884533609356090
38 Sernekos LA. Nutritional treatment of pressure ulcers: what is the
evidence? JAANP 2013; 25(6):281–288. https://doi.
org/10.1002/2327-6924.12025
39 Quain AM, Khardori NM. Nutrition in wound care management: a
comprehensive overview. Wounds 2015; 27(12):327–335
40 Thomas DR. Role of nutrition in the treatment and prevention of
pressure ulcers. Nutr Clin Pract 2014; 29(4):466–472. https://doi.
org/10.1177/0884533614539016
31
Downloaded from magonlinelibrary.com by 147.161.128.113 on February 20, 2024.