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The PDRN (polydeoxyribonucleotide) IN COSMETIC MEDICINE, BIOLOGICAL

INTRODUCTION, LITERATURE AND META-ANALYSIS

Preprint · February 2018

DOI: 10.13140/RG.2.2.15734.70720

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 The PDRN (polydeoxyribonucleotide) IN
COSMETIC MEDICINE, BIOLOGICAL
INTRODUCTION, LITERATURE AND META-
ANALYSIS

Fabiano Svolacchia, M.D. ; Ph.D. Student

Department of Anatomical, Histological, Medical-Legal Sciences and

Locomotor Apparatus, Section of Human Anatomy, Experimental
Morphology Laboratory of the University of Rome "La Sapienza"

BIOLOGICAL PREMISES

As for other scientific fields, Aesthetic Medicine is also linked to a

process that must lead to an answer by applying methods that involve
a valid formulation and that can be verified only by collecting data and
with these last we see that the PDRN used in biorevitalization
treatments or biorestructuring results to be fragments of DNA, very
often without other indications on their length, provisions of bases,
bonds and molecular weight. We can certainly say that they are still
macromolecules, which belong to the second level of cellular
complexity according to a nomenclature that provides as the first there
are organic molecules, the latter in fact the biological macromolecules,
the third supramolecular structures, the fourth the organelles and at the
fifth the cell (Becker, the world of the cell, chap.2) , (12) .
A general principle is that macromolecules are responsible for almost
all the forms and characteristics of living systems and are generated by
the polymerization of small and single organic molecules. The PDRN
or DNA fragments are already informational molecules (1) (13) with
coding function, in fact they contains the information for the specific
cellular activity and must necessarily already be polymerized to exist
in that pharmaceutical form. The nucleotides, physiologically, are
assembled inside the cell according to the availability and the requests
that require it through inorganic precursors, and this represents the
fundamental principle of cell biochemistry.
The DNA complexes, then, as macromolecules, are too large to pass
through the cell membranes because they can present considerable
variations in their structure. For example, from the technical sheet of
one of the products on the market containing PDRN we learn that it
has an average molecular weight of 350. In chemistry the molecular
weight is measured in Dalton and the molecules that can be transported
through the membrane must be weighing less than 350 Daltons
(Becker, the world of the cell, chapter 2). Even if the PDRN had the
ability to cross the cell membrane would undergo a further restriction
linked to the measurement of the nuclear membrane pores, the only
and only point where the DNA fragments could theoretically be
reused, contrary to the RNA fragments also available in the cytoplasm.
To be reused, these DNA fragments should be depolymerized to be
reduced to a single nucleotide, from which to have the single
nucleoside, in order to be able to pass from the cytoplasm into the
nucleus through the nuclear pores (Becher, the world of the cell, chap.
8). Therefore, even if the PDRN complex or part of it passes the
cytoplasmic membrane, the cell would have to depolymerize in single
nucleosides, the material introduced with our mesotherapeutic
technique, to have the possibility of its subsequent reuse (Becker , the
world of the cell, eighth edition, chapters 2,3, 18). Not only the energy
of the hydrolysis derived from the ATP of the individual components
could be used by the cell itself to expel other components in solution
with the PDRN, through the ABC-type ATPase phenomenon known
as a transporter. ABC, which includes ions, sugars (ribose and / or
deoxyribose) amino acids, peptides and polysaccharides (Becher, the
world of the cell, chapter 8 and Pontieri-Russo-Friars ed. IV, chap.2),
with all respect to the attempt to bio-stimulate.But the basic concept is
that the information contained in DNA is used by cells in two steps:
transcription and translation. During transcription RNA is synthesized
and during translation the information contained in the RNA is used to
determine the amino acid sequence of the protein to be produced and
at that time necessary (Becker, the world of the cell, chapter 18). The
cell is induced to activate specific areas of DNA and to translate also
and above all by virtue of external stimuli, through signals that come
from the outside to the nucleus, allowing it to transcribe some genes
(DNA) instead of others. Not to mention 44% repeated or scattered
DNA sequences, introns that are non-coding regions 24%, non-coding
15% unique DNA, 15% repeated tandem DNA and 10% ALU
elements (Becker, the world of cell, chapter 18).

SCIENTIFIC EVIDENCE
Given these premises we can postulate that the PDRN macromolecule
remains completely or partially outside the cells during and after
treatment with the micropomfi mesotherapeutic technique in the Extra
Cytoplasmic Matrix (MEC). Bearing in mind that the extracellular
matrix and the cell wall constitute the outside of the cell and do not
represent the physiological place for the presence of DNA fragments
(Becker, the world of the cell, chap.4) we can state with scientific
rationale that these fragments act also and especially on the cell
membrane and as a dermis on fibroblasts, stimulating them to a
response through the Toll-Like Receptor system, up to possible
granulomatous events (7). Nucleic acid fragments (PDRNs) are
intracellular components, predominantly contained in the nucleus and
partly in the cytoplasm, mitochondria and the rough endoplasmic
reticulum. In the dermis the contact of the PDRN with the fibroblast
surface activates the information signals as if there had been damage
on contiguous cells. It receives biological damage information from
the endocellular materials produced by the damage itself or by the
mediators of inflammation. It is known that inflammation and tissue
damage are strong stimuli for the activation of fibroblasts with the
simultaneous initiation of repairing and fibrous processes, sometimes
even pathological (9). Fibroblasts isolated from fibrotic tissues often
show an abnormal persistent phenotype, characterized by a greater
synthesis of matrix components such as collagen (6) (8). This
metabolic abnormality, apparently, is independent of continuous
exposure to any pathological stimulus that may have initiated the
process (6). The binding of nucleic acid fragments to CD 40 but
especially to CD 39 activates the reparative process with the formation
of scar tissue. Scientific studies with PDRN indicate that there is an
increase in fibroblastic activity up to 30% and relative increase in
collagen, fibronectin and dermal filling (2) (3). PDRN is involved in
the growth and development of tissues and is successfully used in
tissue engineering, increases the expression of VEGF, also
overexpressed in neoplastic cells and that allows them an adequate
vascularization and growth (2) with inhibition of cyclin regulation
employee (3). In a clinical study of the increase in placebo wound
repair, it showed statistical significance, with an increase of 0.008, but
administered daily at a high dose (5625 mg / ampulle ) (4). This
neocollagenogenesis is related to the formation of fibrotic collagen
typical of a scar tissue with tissue repair and not regeneration.
Extracellular nucleotides (PDRNs) stimulate purinergic type 2
receptors and adenosine (purine base) regulates inflammation and
tissue repair. Adenosine receptors play an active role in the
pathogenesis of dermal fibrosis and extracellular nucleotides are
implicated as inflammatory mediators in many pathological situations
(10) (11). Not only that, it has been found that PDRN inhibits IGF-1
and this confirms its uselessness with the use in association with low-
dose insulin treatments (1) , since it inactivates the signaling pathway
of the same receptors (Goodman and Gilman, tenth edition, page 1600
et seq.).
CONCLUSIONS

The PDRN can certainly have a role in aesthetic medicine but must be
placed in its class of specific competence as a restructuring of the
dermal matrix through the increase of fibrotic collagen in a tissue
hypotonia protocol, which also causes further tissue damage, therefore
physiologically negative, it produces a positive aesthetic effect, with
type I neocollagenogenesis. It would be appropriate in virtue of the
reported literature, not to use the PDRN in young subjects or with the
possibility of receiving improvements both aesthetically but also
biological therapies of different approach on the cell to be stimulated
and in any case after having understood the purposes of this therapeutic
approach to the patient , supplemented by adequate informed consent.

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