Potential Tissue Repair of Salmon DNA as Additional Therapy for Improve Outcomes in

Revision Rhinoplasty of Severely Contracted Nose: A Literature Review

Andi Muh. Octavian Pratama1, Anwar Lewa2
1
General Practitioner, Hasanuddin University, Makassar, Indonesia
2
Plastic Reconstructive and Aesthetic Surgery, dr.Esnawan Antariksa Air Force Hospital,
Jakarta, Indonesia

ABSTRACT
The most difficult problem to correct is a severely contracted nose. Severely contracted
nose is manifested with a tight and hardened nasal envelope. These patients present with a
history of nasal infection and subsequent removal of the nasal implant. During the inflammatory
and subsequent contracture stage, a significant amount of the nasal soft-tissue envelope
transforms into scar tissue. PDRN treatment has been found to effectively to promote wound
repair without significant side effects. Furthermore, the last study about PDRN for contracted
Nose showed soften nasal skin and improve skin mobility for improved outcomes in revision
rhinoplasty.
Keyword: Contracted Nose, Polydeoxyribonucleotide (PDRN), Rhinoplasty

Introduction
Contracted nose is a condition that occurs after rhinoplasty when there has been an injury
to the nose. This nose injury can be due to a number of factors. These factors are: 1) capsular
contraction due to silicone implants, 2) Infection, 3) multiple surgeries or 4) patient’s skin
condition.1 These patients present with a history of nasal infection and subsequent removal of the
nasal implant. During the inflammatory and subsequent contracture stage, a significant amount
of the nasal soft-tissue envelope transforms into scar tissue. The scar tissue is present not only in
the sub- cutaneous layer, but also in the dermal layer. Excision of this scar tissue leads to
extreme thinning of the nasal envelope that can compromise blood supply to the overlying skin.
Wide dissection and release of the capsule can correct mild to moderate nasal capsular
contraction but does not adequately expand the nasal envelope in cases of severe contracture for
tension-free red raping during revision surgery.1,2
In the severely contracted nose, the underlying nasal cartilage framework is also
compressed or distorted, and the overall effect is a characteristically shortened nose. Most
patients with contracted nose require revision rhinoplasty and septoplasty, for which preoperative
and/or intraoperative expansion of nasal soft tissue is necessary. Scar tissue formed along the
nose, however, limits the expansion of nasal tissue needed for tension-free revision surgery.1
The introduction of PDRN in clinical practice is not new and its astonishing therapeutic
effects include anti-inflammatory, anti-apoptotic, anti-osteoporotic, anti-melanogenetic, anti-
allodynic, anti-osteonecrotic, bone regenerative, tissue damage preventive, anti-ulcerative,
wound healing, and scar preventive effects.3,4 In the last report, Polydeoxyribonucleotide
(PDRN) injections used to soften nasal skin and improve skin mobility for improved outcomes in
revision rhinoplasty and septoplasty.5

Polydeoxyribonucleotide (PDRN) For Tissue Repair

Polydeoxyribonucleotide (PDRN) is a DNA-derived drug from Oncorhynchus mykiss
(Salmon trout) or Oncorhynchus keta (Chum Salmon) sperm with molecular weights between 50
and 1500 KDa and a chain length ranging from 50 bp to 2000 bp. The drug is obtained through
an extractive process at a high temperature in order to purify the substance and ensure a very
high percentage of DNA. The final product is a >95% pure active principle without
pharmacologically active proteins and peptides (Registration Dossier, Italian Ministry of
Health).3,4 Furthermore, PDRN has been shown to enhance the growth rate of numerous cells
such as fibroblasts, chondrocytes, preadipocytes and osteoblasts in primary cultures at
therapeutic concentrations.6 All these favorable effects on cell proliferation enhancement appear
to be mediated by the salvage metabolic pathways and by the activation of adenosine receptors
A2a that has been shown to accelerate the resolution of acute inflammation, upregulate VEGF
promoting vessel formation by endothelial cells and support granulation tissue formation.11,12

Figure 1. Mechanism of Polydeoxyribonucleotide for tissue regeneration and wound

healing

In another study, PDRN promoted the production of interleukin 10 (IL-10), an anti-

inflammatory cytokine, and suppressed the production of nitric oxide and release of pro-
inflammatory cytokines, interleukin 12 (IL-12), and tumor necrosis factor alpha (TNF-α). PDRN
has near-miraculous tissue-repair properties. It can improve the skin repair process by markedly
increasing the expression of the vascular endothelial growth factor (VEGF), a master regulator of
angiogenesis.9 PDRN stimulates VEGF production by activating the adenosine A 2A receptor. The
resulting increase in CD31, transglutaminase-II, and angioprotein levels is suggestive of
angiogenesis improvement. The healing effect of PDRN was found to be nullified by dimethyl-1-
propargylxanthine (DMPX), a selective adenosine A2A receptor antagonist, confirming the
involvement of the adenosine A2A receptor.8,9

Treatment with PDRN does improve collagen synthesis. A recent study investigated the
increase in fibroblast collagen and elastin synthesis via the inhibition of MMP-1; the decrease in
MMP activity resulted in an increase in collagen synthesis. 8 MMPs play an important role in
elastin degradation, and an increase in MMPs is associated with damage to ECM components.
As mentioned above, PDRN inhibits the expression of MMP-1 and elastase. These two factors
play a key role in skin aging and wrinkling. Elastase is a protease responsible for the breakdown
of elastic fibers. The overexpression of elastase results in a loss of skin elasticity. An increase in
elastase activity with age was found in the skin of mice. Therefore, elastase inhibition can slow
down the process through which aging skin loses its elasticity. MMP-1 is also involved in the
breakdown of the ECM, thus the inhibition of MMP-1 via PDRN can also favor the maintenance
of skin elasticity.6.7.8,12

The Potential of Salmon DNA/ Polydeoxyribonucleotide (PDRN) for Severely Contracted

Nose
There are two factors that need to be addressed in the correction of the severely
contracted nose. One is expansion of the constricted nasal envelope, and the other is
reestablishment of the desired stable internal framework. Expansion of the soft tissue in the
contracted nose needs to be sufficient to allow for tension-free redraping during revision
augmentation.1 And, there are two ways to expand the nasal skin envelope. One is intraoperative
expansion by means of wide dissection; the other is by softening the nasal envelope before
surgery. First, in the mild or moderately contracted nose, intraoperative expansion by means of
wide dissection of the nasal envelope from the surrounding cartilages, bone, and retaining
ligaments is often sufficient to allow for tension-free redraping.1-2

Table 1. Classification of nasal capsular contracture after augmentation rhinoplasty2

Grad Description
e
1 Natural appearance. No skin color change, hardness, or irregularity
2 Minimal contracture. Unnatural lateral margin and look, but the appearance is
acceptable to the patient.
3 Moderate contracture. Implant deviation with skin hardness and irregularity
4 Severe contracture. Contracted nose and short nose deformity with nostril show

However, in the severely contracted nose, the tight constricted nasal envelope does not
expand adequately even with wide dissection. The limiting factor is the intrinsic thickening of
the entire nasal envelope, including the skin. Even if the nasal envelope is maximally expanded
intraoperatively, the tight nasal skin exerts pressure on the reconstructed internal framework,
especially at the tip. Second, the vascular supply to the nasal envelope is tenuous from multiple
surgical traumas and inflammation. Aggressive wide undermining may compromise the blood
supply to the nose.1
PDRN activates the adenosine A2A receptor that stimulates fibroblast differentiation and
maturation and the release of vascular endothelial cell growth factor for neo-vascularization.
PDRN treatment has been found to effectively enhance the survival of skin flaps, promote hair
restoration, and promote wound repair without significant side effects. There is a study evaluated
the efficacy and safety of pre- and postoperative adjuvant therapy using polydeoxyribonucleotide
(PDRN) and invasive, pulsed-type, bipolar, alternating current radiofrequency (RF) for revision
surgery of a contracted nose (Figure 2-5).5

Figure 2-5. Case 1 Contracted nose in a 52-year-old female patient. Patient had 8 sessions of
preoperative and 8 sessions of postoperative adjuvant therapy using PDRN and invasive bipolar
RF. Clinical photographs at baseline (A) and at 18 months after revision surgery (B). Case 2
Contracted nose in a 62-year-old female patient. Patient had 8 sessions of preoperative and 8
sessions of postoperative adjuvant therapy using PDRN and invasive, pulsed-type, bipolar,
alternating current RF. Clinical photographs at baseline (C) and at 18 months after revision
surgery (D).5

PDRN was injected into the contracted nose at a dose of 0.3 mL/session at 1-week
intervals, followed by invasive bipolar RF treatments. This study explained, Patient had 8
sessions of preoperative and 8 sessions of postoperative adjuvant therapy using PDRN and
invasive bipolar RF. PDRN-induced angiogenesis and invasive bipolar RF-induced wound repair
seemed to remarkably soften the contracted skin and improve skin mobility. Furthermore, the
repetitive generation of tissue wounding with minimal thermal coagulation by pulsed- type RF
significantly maximized the utilization of PDRN in the contracted nasal skin. In our experience,
preoperative adjuvant therapy noticeably shortens the preparatory period for revision surgery,
and postoperative adjuvant therapy prevents further tissue contracture by the revision surgery.5
Conclusion
Based on its well-known mechanism of action, PDRN can potentially improve in tissue
repair, skin quality, improve dermal regeneration and remarkably improved the therapeutic
outcomes of revision rhinoplasty for contracted skin of the nose without major side effects.
Further, properly designed, controlled clinical trials are needed to confirm the effectiveness and
optimize the pre- and postrevision surgery adjuvant therapies in patients with severely contracted
nose in a wider population.

Financial Support and Sponsorship

Nil

Conflicts of interest
There are no conflicts of interest.

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