Challenges in Practice

J Wound Ostomy Continence Nurs. 2018;45(4):359-363.

Published by Lippincott Williams & Wilkins

Biological Approach for Managing Severe Gunshot

Wounds
A Case Report
Victoria Muñoz ¿ Carmen Martinez ¿ Begoña Echevarria ¿ Mª Isabel Fernández ¿ Ander Pino ¿ Eduardo Anitua

ABSTRACT
BACKGROUND: Autologous formulations rich in bioactive proteins promote cutaneous tissue regeneration. This case report
describes our experiences with a platelet-based autologous formulation in the management of a hard-to-heal and severe gunshot
wound.
CASE: A healthy, 34-year-old man suffered an accidental gunshot wound of his right foot. After cleansing with saline and
application of vacuum-assisted closure therapy for a period of 5 weeks, the resulting full-thickness wound had a surface area of
20 cm2 and did not show progress toward closure despite ongoing treatment. Plasma-rich growth factor (PRGF) therapy was
used in order to promote tissue regeneration. The patient’s own blood was drawn, centrifuged, and platelet-rich plasma was
obtained. Intradermal injections of freshly activated platelet-rich plasma were administered into the wound edges, and a fibrin
membrane was applied on the wound bed. Afterward, a novel topical ointment based on the patient’s own growth factors was
used as a daily therapy over the affected tissue.
RESULTS: This full-thickness wound healed after 16 weeks of autologous growth factor therapy. The patient was able to walk
without pain.
CONCLUSION: Plasma-rich growth factor therapy successfully healed this full-thickness wound that did not respond to a
period of 5 weeks with negative pressure wound therapy using a vacuum-assisted device. Healing occurred after 16 weeks of
treatment, and he was able to resume walking without pain or functional deficits.
KEY WORDS: Gunshot injury, Platelet-rich plasma, Platelet-derived growth factor, Skin regeneration, Wound healing.

INTRODUCTION wounds is essential to minimize morbidity and reduce the eco-

Wound healing is a major concern for healthcare systems
worldwide. Normal healing is commonly described as 4 over-
lapping and coordinated stages: hemostasis, inflammation,
proliferation, and remodeling. These phases involve the efforts
of several cell types including keratinocytes, fibroblasts, endo-
thelial cells, macrophages, and platelets.1 However, the micro-
environment of some wounds may paradoxically impair tissue
regeneration and healing. Full-thickness wounds are character-
ized by loss of both epidermal and dermal layers, and they usu-
ally involve damage to subcutaneous adipose tissue and deeper
structures. Prompt and successful treatment of full-thickness
Victoria Muñoz, BS, Quirónsalud Hospital Bizkaia, Erandio, Spain.
Carmen Martinez, BS, Quirónsalud Hospital Bizkaia, Erandio, Spain.
Begoña Echevarria, BS, Quirónsalud Hospital Bizkaia, Erandio, Spain.
Mª Isabel Fernández, BS, Quirónsalud Hospital Bizkaia, Erandio, Spain.
Ander Pino, MSc, BTI Biotechnology Institute, Vitoria, Spain.
Eduardo Anitua, PhD, MD, DDS, BTI Biotechnology Institute, Vitoria, Spain
and Eduardo Anitua Foundation, Vitoria, Spain.
Eduardo Anitua is the scientific director of, and Ander Pino is a researcher at,
BTI Biotechnology Institute, the company that has developed the PRGF-
Endoret technology. Victoria Muñoz, Carmen Martinez, Begoña Echevarria, and
Mª Isabel Fernandez declare no conflict of interest.
Correspondence: Eduardo Anitua, PhD, MD, DDS, Fundación Eduardo Anitua,
Jacinto Quincoces 39, Vitoria, Spain (eduardoanitua@eduardoanitua.com).
DOI: 10.1097/WON.0000000000000451
nomic burden on public health.2
Plasma-rich growth factor (PRGF) technology is based
on withdrawal of a small volume of the patient’s own
blood; this sample is then centrifuged in order to obtain
a platelet-concentrated fraction rich in autologous growth
factors.3,4 The versatility of PRGF allows in situ applica-
tion of different biological formulations with potential
wound-healing and tissue regenerative activities; these
formulations have also been shown to exert anti-inflam-
matory and antimicrobial activities.5-9 The dermatological
use of PRGF has been clinically tested on recalcitrant skin
wounds such as full-thickness pressure injuries, venous leg
ulcers, diabetic foot ulcers, and in wounds associated with
sickle cell disease and trasns-sphincteric cryptoglandular
fistulae.10-18
Platelets contain a wide variety of key proteins needed
for tissue regeneration, including epidermal growth factor
(EGF), fibroblast growth factor-2 (FGF-2), transforming
growth factor-β (TGF-β), vascular endothelial growth fac-
tor (VEGF), and platelet-derived growth factor (PDGF).19
These macromolecules are involved in a number of bio-
logical mechanisms that promote wound healing such as
reepithelization, granulation tissue formation, stem cell
recruitment, angioneogenesis, and extracellular matrix re-
modeling.20 Apart from releasing a wide range of morpho-
gens, PRGF enables the intradermal development of a bio-
compatible fibrin scaffold that acts as a biological membrane

Copyright © 2018 by the Wound, Ostomy and Continence Nurses Society™ JWOCN ¿ July/August 2018 359

Copyright © 2018 Wound, Ostomy and Continence Nurses Society™. Unauthorized reproduction of this article is prohibited.
360 JWOCN ¿ July/August 2018 www.jwocnonline.com

that maintains a sustained and controlled release of growth
factors during several days.21,22
Gunshot wounds often create complete loss of cutaneous
tissue, with exposure of tendons, bone surface. In many cases,
it is hard to obtain a complete healing because of the complex-
ity and variety of affected tissues and the presence of foreign
bodies that increase the risk for infection and delay wound
healing.23 Treatment usually involves systemic and/or local an-
tibiotic therapy to prevent infection, stabilization of damaged
bones, and debridement of soft tissue injuries. Management
frequently includes autologous skin grafts/flaps and negative
pressure wound therapy.24,25 This case study describes our ex-
perience with management of a severe gunshot and nonheal-
ing wound using PRGF therapy.
CASE
Mr V. was a healthy 34-year-old man who was accidentally
shot with a hunting rifle; the bullet struck his right foot. The
resulting wound comprised a circular area of 20 cm2 located
on the dorsal surface between the second and third metatar-
sal heads. X-ray imaging showed a comminuted fracture of
the second metatarsal with shrapnel and partial fracture of
the third metatarsal bone. Although the first, fourth, and fifth
toes remained intact with preserved sensitivity, the second and
third toes had a pale appearance and hypoesthesia. The depth
of the wound also affected the plantar surface of the foot as is
shown in Figures 1A and 1B.
Mr V. visited several medical centers during a 3-week pe-
riod following his gunshot wound. The wound was surgically
debrided, and warmed normal saline (sodium chloride 0.9%)
and moist sterile gauze dressings were then applied over the
damaged area. Dressings were applied with minimum me-
chanical force to avoid friction or rubbing against the wound
bed. The wound was then covered with silicone dressings
(Linitul; Bama Geve, Barcelona, Spain), which was, in turn, cov-
ered with a compression bandage. In addition, he received paren-
teral cefazolin (1 g/6 h) and gentamicin (200 mg/24 h) during a
2 days’ hospital course. He was discharged with the following
medications: enoxaparin (40 mg/24 h) and dexketoprofen

Figure 1. Acute full-thickness gunshot wound treated with PRGF therapy. (A, B) Dorsal and plantar surfaces of the right foot showing
the severity of the wound before the beginning of the treatment with PRGF. (C) Intradermal infiltration of freshly activated plasma rich in
growth factors into the edges of the wound. (D) Bioactive protein releasing fibrin scaffold placed onto the wound bed. (E, F) Dorsal and
plantar wound healing after 2 months of PRGF therapy. PRGF indicates plasma-rich growth factor.

Copyright © 2018 Wound, Ostomy and Continence Nurses Society™. Unauthorized reproduction of this article is prohibited.
JWOCN ¿ Volume 45 ¿ Number 4 Muñoz et al 361

(25 mg/8 h) for pain, omeprazole (20 mg/24 h) for pre-
vention of gastric ulcers, and amoxicillin–clavulanic acid
(875mg-125mg/8 h) for prevention of infection.
After 4 weeks of treatment without apparent progress to-
ward wound closure, Mr V. was admitted to Hospital Quiron
Bizkaia (Bilbao, Spain). Admission assessment revealed mild
maceration of the plantar aspect of the wound while the dor-
sal area was characterized by necrotic slough and high-volume
exudate. After careful cleaning with chlorhexidine and saline,
negative pressure wound therapy using a vacuum-assisted clo-
sure device was applied over the wound area for 2 weeks with
intercalated nitrofurazone discs.
Members of the plastic surgery department considered re-
moving the residual bone of the second toe and performing a
skin flap. Assuming the potential detrimental effect on our pa-
tient’s ambulation from the planned surgery, combined with the
risk of flap survival failure, we proposed treatment with PRGF
in an attempt to provoke tissue regeneration and wound healing.
Mr V. was counseled about the procedure in detail and
informed consent was obtained before beginning PRGF
therapy. Both dorsal and plantar wounds were treated with
PRGF using techniques described previously.10,11 Six week-
ly interventions were carried out. Eighteen milliliters of
peripheral blood was obtained and placed in 9-mL tubes
containing 3.8% (wt/vol) sodium citrate. The blood was
centrifuged (BTI System IV, Vitoria, Spain) at 580 g for 8
minutes, and the plasma column was divided into 2 frac-
tions (F1 and F2). Fraction 2 comprised 2 mL of plate-
let-rich plasma retrieved from above the leukocyte buffy
coat, and F1 comprised the remaining plasma volume
above F2. Leukocytes of the buffy coat over the red blood
cell column were not collected in order to prevent their
proinflammatory effects during treatment.
A PRGF activator (BTI Biotechnology Institute SL, Vitoria,
Spain) was added to 1 to 2 mL of F2 for platelet activation,
and the mixture was immediately injected into the margins of
the wound using 30-G needles. The remaining F2 fraction was
activated, allowed to clot ex vivo, and placed on the wound
bed as an autologous fibrin scaffold. The remaining portion
of F1 was also activated and mixed with sterile gauzes to form
a fibrin membrane that was used as transient wound dressing
with a final hydrocolloid bandage (Figures 1C and 1D). In
all cases, the time elapsed between venipuncture and wound
treatment was less than 1 hour.
Within 5 weeks of beginning PRGF therapy, the dor-
sal wound had healed significantly. Assessment of the dorsal
wound revealed a noticeable reepithelized surface, along with
reductions in the depth of the wound and production of ex-
udate, indicating progress toward closure. The dorsal wound
now covered an area of 3 cm2, and the plantar wound had
closed and was covered with scar (Figures 1E and 1F). At this
point, Mr V. underwent a second phase of PRGF therapy.
Eight tubes of peripheral blood were obtained and frac-
tionated as described earlier. Based on the PRGF procedures
described earlier, we developed a novel topical ointment. The
resulting formulation was autologous, biocompatible, and
rich in growth factors. We found that its viscosity facilitated
spreading it over the affected surfaces in a manner designed to
fill remaining tissue defects. A total of 24 mL of topical oint-
ment was generated and stored at 4°C for subsequent treat-
ment; this avoided the need for additional blood extraction.
This biological and personalized ointment was applied over
the surface of the dorsal wound (1-2 mL per dose) at 3- to
4-day intervals over an 8-week period. In contrast, the cica-
trized plantar wound was cleansed with physiological saline.
After each dose, the foot was covered with foam dressings

Figure 2. Acute full-thickness gunshot wound treated with PRGF therapy. (A) Repeated applications of a growth factor–rich topical
ointment onto the surface of the wound. (B) Dressing technique used between the ointment application doses. (C, D) Complete
healing of the dorsal-plantar full-thickness wound after 4 months of the beginning of the PRGF therapy. PRGF indicates plasma-rich
growth factor.

Copyright © 2018 Wound, Ostomy and Continence Nurses Society™. Unauthorized reproduction of this article is prohibited.
362 JWOCN ¿ July/August 2018
(Figures 2A and 2B). After 16 weeks of PRGF therapy, the
dorsal wound had closed and Mr V. was able to walk without
pain or detectable abnormalities in gait (Figures 2C and 2D).
DISCUSSION
Plasma-rich growth factor therapy has been successfully used
to promote tissue regeneration following maxillofacial surgery,
and in ophthalmology, traumatology, and sports medicine.26-29
Platelet-derived proteins and autologous fibrin membranes
have also been used in regenerative dermatology for treatment
of chronic nonhealing ulcers due to variable etiologies.30,31
Several groups state that the use of platelet-rich plasma not
only reduces the duration and costs of treatment but it also
reduces the number of dressings and postsurgical infections/
complications and shortens surgery hospital stays.32,33
Autologous growth factors have also been proved benefi-
cial in patients with traumatic wounds.34-37 The use of plate-
let-rich plasma has the potential to prevent wounds at risk
for impaired healing from developing postoperative compli-
cations, and research into its use as a prophylactic approach
is an intriguing possibility.38 Several studies have shown that
platelet-rich plasma promotes dermal fibroblast mitogenic
and chemotactic activities along with collagen and hyaluronic
acid biosynthesis.39,40 These actions may be related to overex-
pression of cyclin A and cyclin-dependent kinase-4 (CDK-4)
proteins in acute wounds after growth factor treatment.41 In
addition, many of the bioactive proteins found in platelet-rich
plasma such as vascular endothelial growth factor (VEGF),
hepatocyte growth factor (HGF), insulin like growth factor
(IGF), or connective tissue growth factor (CTGF) have been
shown to be involved in key biomolecular mechanisms such
as stem cell chemoattraction/differentiation and microvascu-
lature development.42
Our experiences with this case also suggest that PRGF
promotes cutaneous tissue regeneration even in hard-to-se-
vere and nonhealing traumatic wounds. The protocol for ther-
apy using PRGF includes repeated intradermal injections of
plasma proteins combined with application of a fibrin scaffold
rich in growth factors to the wound bed. Finally, we applied a
novel topical ointment obtained from the patient’s own blood
daily. We believe that rapid formation of granulation tis-
sue and vascular supply is essential for the healing of
such traumatic wounds. It has been observed that plate-
let-rich plasma induces a proangiogenic response via the
angiopoietin-I/Tie-2 signaling pathway that promotes mi-
gration of leading cells that guide the direction of primary
capillaries and differentiation of trailing cells essential to
creating a lumen for new capillaries.43 Additional studies are
needed to correlate the angiogenic effect of PRGF as a pivot-
al mechanism in gunshot wounds. However, the molecular
pathways triggered by the release of proteins such a VEGF
and PDGF might be involved in accelerated healing of these
types of wounds.44
An ideal scaffold should promote rapid remodeling, inhibit
infection, increase tissue strength, and permit early rehabili-
tation. Limited evidence suggests that other gunshot injuries
treated with autologous proteins provide antimicrobial mol-
ecules to the affected area as well as increase wound closure
velocity, rapid epithelization, and microvascular endothelial
cell replication.38,45,46 Although these mechanisms might have
been involved in the wound healing in our patient, additional
Copyright © 2018 Wound, Ostomy and Continence Nurses Society™. Unauthorized reproduction of this article is prohibited.
www.jwocnonline.com
research is needed before the efficacy and real therapeutic effect
of PRGF on gunshot or traumatic wounds can be established.
CONCLUSIONS
Our results demonstrate that management with intradermal,
clot released, and topically applied autologous PRGF was well
accepted by a patient with a nonhealing gunshot wound. Nev-
ertheless, conclusions derived from this single case study are
limited. Although further research including randomized clin-
ical trials with carefully specified doses and application proto-
cols are needed, this case report suggests that PRGF may be
effective therapy for treatment of patients with full-thickness
traumatic wounds.
4 KEY POINTS
h Autologous formulations rich in bioactive proteins have
been shown to promote cutaneous tissue regeneration
in in vivo and in vitro studies.
h Our experience with this patient suggests that PRGF
may be safe and effective for management of nonheal-
ing traumatic wounds.
h Additional research is needed to determine the safety
and efficacy of autologous formulations in the treat-
ment of traumatic wounds and possibly in prevention
of postoperative complications in patients undergoing
surgery for treatment of these wounds.
REFERENCES
1. Ziegler TR, Pierce GF, Herndon DN. Growth Factors and Wound Heal-
ing: Basic Science and Potential Clinical Applications. New York, NY:
Springer Science & Business Media; 2012.
2. Guest JF, Ayoub N, McIlwraith T, et al. Health economic burden that
wounds impose on the National Health Service in the UK. BMJ Open.
2015;5(12):e009283.
3. Anitua E, Andia I, Ardanza B, Nurden P, Nurden AT. Autologous
platelets as a source of proteins for healing and tissue regeneration.
Thromb Haemost. 2004;91(1):4-15.
4. Anitua E. Plasma rich in growth factors: preliminary results of use in
the preparation of future sites for implants. Int J Oral Maxillofac Im-
plants. 1999;14(4):529-535.
5. Anitua E, Alonso R, Girbau C, Aguirre J, Muruzabal F, Orive G. Anti-
bacterial effect of plasma rich in growth factors (PRGF® Endoret®)
against Staphylococcus aureus and Staphylococcus epidermidis
strains. Clin Exp Dermatol. 2012;37(6):652-657.
6. Anitua E, Muruzabal F, de la Fuente M, Riestra A, Merayo-Lloves J,
Orive G. PRGF exerts more potent proliferative and anti-inflammatory
effects than autologous serum on a cell culture inflammatory model.
Exp Eye Res. 2016;151:115-121.
7. Anitua E, Sánchez M, Orive G. Potential of endogenous regenera-
tive technology for in situ regenerative medicine. Adv Drug Deliv Rev.
2010;62(7):741-752.
8. Anitua E, Sánchez M, Orive G, Andia I. Delivering growth factors for
therapeutics. Trends Pharmacol Sci. 2008;29(1):37-41.
9. Anitua E, Zalduendo M, Troya M, Padilla S, Orive G. Leukocyte inclu-
sion within a platelet rich plasma-derived fibrin scaffold stimulates a
more pro-inflammatory environment and alters fibrin properties. PLoS
One. 2015;10(3):e0121713.
10. Aguirre JJ, Anitua E, Francisco S, Cabezas AI, Orive G, Algorta J.
Efficacy and safety of plasma rich in growth factors in the treatment of
venous ulcers: a randomized clinical trial controlled with conventional
treatment. Clin Dermatol. 2015;3(1):13-20.
11. Anitua E, Aguirre JJ, Algorta J, et al. Effectiveness of autologous
preparation rich in growth factors for the treatment of chronic cu-
taneous ulcers. J Biomed Mater Res B Appl Biomater. 2008;84(2):
415-421.
JWOCN ¿ Volume 45 ¿ Number 4
12. Cardeñosa ME, Domínguez-Maldonado G, Córdoba-Fernández A. Ef-
ficacy and safety of the use of platelet-rich plasma to manage venous
ulcers. J Tissue Viability. 2017;26(2):138-143.
13. de la Portilla F, Segura-Sampedro J, Reyes-Díaz M, et al. Treatment
of transsphincteric fistula-in-ano with growth factors from autolo-
gous platelets: results of a phase II clinical trial. Int J Colorectal Dis.
2017;32(11):1545-1550.
14. Gilli SC, do Valle Oliveira SA, Saad STO. Autologous platelet gel: five
cases illustrating use on sickle cell disease ulcers. Int J Lower Extrem
Wounds. 2014;13(2):120-126.
15. Orcajo B, Muruzabal F, Isasmendi MC, et al. The use of plasma rich
in growth factors (PRGF-Endoret) in the treatment of a severe mal
perforant ulcer in the foot of a person with diabetes. Diabetes Res Clin
Pract. 2011;93(2):e65-e67.
16. Ramos-Torrecillas J, De Luna-Bertos E, García-Martínez O, Díaz-
Rodríguez L, Ruiz C. Use of platelet-rich plasma to treat pressure
ulcers: a case study. J Wound Ostomy Continence Nurs. 2013;40(2):
198-202.
17. Ramos-Torrecillas J, García-Martínez O, De Luna-Bertos E,
Ocaña-Peinado FM, Ruiz C. Effectiveness of platelet-rich plasma and
hyaluronic acid for the treatment and care of pressure ulcers. Biol Res
Nurs. 2015;17(2):152-158.
18. Sokolov T, Valentinov B, Andonov J, Angelov S, Kosev P. Contam-
inated problematic skin wounds in diabetic patients treated with
autologous platelet-rich plasma (PRP): a case series study. J IMAB.
2016;22(1):1067-1071.
19. Barrientos S, Stojadinovic O, Golinko MS, Brem H, Tomic Canic M.
Growth factors and cytokines in wound healing. Wound Repair Regen.
2008;16(5):585-601.
20. Piccin A, Di Pierro AM, Canzian L, et al. Platelet gel: a new therapeutic
tool with great potential. Blood Transfus. 2017;15(4):333.
21. Anitua E, Pino A, Jaen P, Orive G. Plasma rich in growth factors en-
hances wound healing and protects from photo-oxidative stress in
dermal fibroblasts and 3D skin models. Curr Pharm Biotechnol. 2016
;17(6):556-570.
22. Anitua E, Zalduendo M, Prado R, Alkhraisat M, Orive G. Morphogen
and proinflammatory cytokine release kinetics from PRGF- Endoret
fibrin scaffolds: evaluation of the effect of leukocyte inclusion. J
Biomed Mater Res A. 2015;103(3):1011-1020.
23. Stuehmer C, Blum KS, Kokemueller H, et al. Influence of differ-
ent types of guns, projectiles, and propellants on patterns of
injury to the viscerocranium. J Oral Maxillofac Surg. 2009;67(4):
775-781.
24. Ho J, Walsh C, Yue D, Dardik A, Cheema U. Current advancements
and strategies in tissue engineering for wound healing: a comprehen-
sive review. Adv Wound Care. 2017;6(6):191-209.
25. Salzano A, De Rosa A, Rossi E, et al. The topicality and use of the
radiological exam in gunshot wounds of the limbs. An assessment of
132 cases. Radiol Med. 1999;98(6):468-471.
26. Del Fabbro M, Corbella S, Taschieri S, Francetti L, Weinstein
R. Autologous platelet concentrate for post-extraction sock-
et healing: a systematic review. Eur J Oral Implantol. 2014;7(4):
333-344.
27. Del Fabbro M, Gallesio G, Mozzati M. Autologous platelet concen-
trates for bisphosphonate-related osteonecrosis of the jaw treatment
and prevention. A systematic review of the literature. Eur J Cancer.
2015;51(1):62-74.
28. Anitua E, Muruzabal F, Tayebba A, et al. Autologous serum and plas-
ma rich in growth factors in ophthalmology: preclinical and clinical
studies. Acta Ophthalmol. 2015;93(8):e605-e614.
Copyright © 2018 Wound, Ostomy and Continence Nurses Society™. Unauthorized reproduction of this article is prohibited.
Muñoz et al 363
29. Anitua E, Sánchez M, Aguirre JJ, Prado R, Padilla S, Orive G. Effica-
cy and safety of plasma rich in growth factors intra-articular infiltra-
tions in the treatment of knee osteoarthritis. Arthroscopy. 2014;30(8):
1006-1017.
30. Gonchar I, Lipunov A, Afanasov I, Larina V, Faller A, Kibardin A. Plate-
let rich plasma and growth factors cocktails for diabetic foot ulcers
treatment: state of art developments and future prospects. Diabetes
Metab Syndr. 2018;12(2):189-194.
31. Lacci KM, Dardik A. Platelet-rich plasma: support for its use in wound
healing. Yale J Biol Med. 2010;83(1):1.
32. Cobos R, Aizpuru F, Parraza N, Anitua E, Orive G. Effectiveness and
efficiency of platelet rich plasma in the treatment of diabetic ulcers.
Curr Pharm Biotechnol. 2015;16(7):630-634.
33. Obolenskiy VN, Ermolova DA, Laberko LA. Clinical and economic ef-
fectiveness of the use of platelet-rich plasma in the treatment of chron-
ic wounds. Wound Med. 2017;19:27-32.
34. Tehranian A, Esfehani-Mehr B, Pirjani R, Rezaei N, Heidary SS, Sep-
idarkish M. Application of autologous platelet-rich plasma (PRP) on
wound healing after caesarean section in high-risk patients. Iran Red
Crescent Med J. 2016;18(7):e34449.
35. Pignalosa O, Martusciello D, De Pascale MR, et al. Platelet gel in a
non-regenerating cryosurgery-induced skin wound in an old patient: a
case report. Med Princ Pract. 2016;25(4):388-390.
36. SanGiovanni TP, Kiebzak GM. Prospective randomized evalua-
tion of intraoperative application of autologous platelet-rich plasma
on surgical site infection or delayed wound healing. Foot Ankle Int.
2016;37(5):470-477.
37. Law JX, Chowdhury SR, Saim AB, Idrus RBH. Platelet-rich plasma
with keratinocytes and fibroblasts enhance healing of full-thickness
wounds. J Tissue Viability. 2017;26(3):208-215.
38. Hom DB, Linzie BM, Huang TC. The healing effects of autologous
platelet gel on acute human skin wounds. Arch Facial Plast Surg.
2007;9(3):174-183.
39. Anitua E, Pino A, Orive G. Plasma rich in growth factors promotes
dermal fibroblast proliferation, migration and biosynthetic activity. J
Wound Care. 2016;25(11):680-687.
40. Chen F, Chen M, Yan T, Hou J, Yang J. Effects and mechanism of
allogeneic platelet rich plasma on collagen synthesis in wound healing.
Zhonghua Wai Ke Za Zhi. 2017;55(4):303.
41. Kim S, Ryu HW, Lee KS, Cho JW. Application of platelet-rich plasma
accelerates the wound healing process in acute and chronic ulcers
through rapid migration and upregulation of cyclin A and CDK4 in Ha-
CaT cells. Mol Med Rep. 2013;7(2):476-480.
42. Fernandez-Moure JS, Van Eps JL, Cabrera FJ, et al. Platelet-rich
plasma: a biomimetic approach to enhancement of surgical wound
healing. J Surg Res. 2017;207:33-44.
43. Martínez CE, Smith PC, Palma Alvarado VA. The influence of
platelet-derived products on angiogenesis and tissue repair: a concise
update. Front Physiol. 2015;6:290.
44. Bhang SH, Park J, Yang HS, Shin J, Kim B-S. Platelet-rich plas-
ma enhances the dermal regeneration efficacy of human adipose-
derived stromal cells administered to skin wounds. Cell Transplant.
2013;22(3):437-445.
45. Bayer A, Lammel J, Lippross S, et al. Platelet-released growth factors
induce psoriasin in keratinocytes: implications for the cutaneous barri-
er. Ann Anat. 2017;213:25-32.
46. Cervelli V, Gentile P, Brinci L, Di Pasquali C, Bocchini I, De Angelis
B. Use of platelet rich plasma (PRP) and hyaluronic acid in treat-
ment of extremity gunshot injuries: a case report. World J Plast Surg.
2016;5(1):80.