ABSTRACT
Collagen is one of the natural biomaterials used in cosmetic preparation. It is the most abundant
protein in mammals which is obtained from many sources such as bovine, porcine and human.
Collagen based cosmetics are in demand now a days though safety issues related with allergies
are still main concern of consumers. The collagen is used for different purposes in cosmetic and
medical field such as dermal filler, skin substitute and facial products. Use of collagen in medical
field is useful depending upon the patient’s requirement. It is useful in pathological conditions like in
severely burn patients, patients with chronic wounds such as foot ulcers due to diabetes and
venous leg ulcers etc however, use of collagen injection as anti-aging/anti-wrinkle biomaterial need
to be further investigated in large population study to check the side effects in long term.
Keywords: Dermal filler; scaffolding; skin care product.
1. INTRODUCTION
Cosmetic products and preparations were used
by people since they get aware about their looks
(regardless of the gender). The US Federal
Food, Drug and Cosmetic Act written in 1938,
defined cosmetic as an “articles intended to be
rubbed, poured, sprinkled, or sprayed on,
introduced into, or otherwise applied to the
human body or any part for cleansing,
beautifying, promoting attractiveness, or altering
the appearance”, without affecting any structure
or function of the body [1]. Studies on cosmetics
have been grown rapidly together with the
advancement in science and technology.
Advancement in science and technology allows
many new discoveries including the uses of
biomaterials for cosmetic purposes.
The objective of this review is to emphasize on
the effect of collagen that is commercially used
for cosmetic purposes, clinical benefits of
collagen and to compare the advantages and
disadvantages of the collagen in a cosmetic
products.
2. COLLAGEN
Collagen is a type of protein that has found
abundantly in the extracellular matrix and about
80 to 90% in dermis is type I collagen [2,3]. The
structure of each collagen has a characteristics
feature in which it is comprised of three α-chains.
Each α-chains is composed of thousands of
amino acid to form polypeptide chains based on
the sequence –Gly-X-Y [4]. The glycine (Gly) is
located at every third position and it allows tight
packaging along the molecules. The X and Y
position is usually occupied by proline and
hydroxyproline amino acids. There are more
than 28 different types of collagen that
have been reported [5]. Collagen are of
different types: such as fibril-forming, network
forming, fibril-associated collagens with
interrupted triple helices (FACIT), membraneassociated
collagens with interrupted triple
helices (MACIT) and multiple triple-helix domains
and interruptions (MULTIPLEXINs) [6,7,8,9].
Collagen has been classified based on the
diversity of its structure, function, complexity and
the combination of the α-chains as shown in
Table 1.
Collagen is chosen to be used in cosmetic
industry due to its biodegradability, availability
and biocompatibility. The common sources of
collagen are bovine, porcine, human collagen
and marine organism such as scale fish [10,11]
and fish skin [12]. The collagen can be used for
different purposes such as in dermal filler, skin
substitute or scaffolding, wound repair and facial
product.
3. APPLICATIONS OF COLLAGEN IN
COSMETICS
3.1 Dermal Filler/ Cosmetic Filler
Dermal filler is commercially used for several
purposes such as for the soft tissue
augmentation, cosmetic surgery, face and hand
rejuvenation, to improve volume deficiencies and
to improve on contour of face [13,14,15]. The
dermal filler will be injected into the deep
dermis or the fatty tissues of the particular part
of the body [16]. Some of the dermal
fillers require pre-treatment before the filler is
injected. The most common type of collagen
being used is bovine, porcine and human. In late
1980s, the first injectable filler approved by US
FDA was bovine collagen-based filler [17]. It was
followed by the approval of other dermal fillers
such as human CosmoDerm®, porcine
Evolence™, and Bovine Zyderm® [13]. In the
United States, the use of soft tissue filler has
increased by 3% from 2013 and then collagen
become one of the source of the fillers as shown
in Fig. 1 [18].
3.2 Skin Substitute/ Scaffolding
Skin substitute is required especially when the
patient is suffered with severe burns (full
thickness). This could happen when there is not
enough donor skin to cover the wound hence
tissue engineering method is considered as one
of the option [19].
3.3 Skin Care Product
Skin-aging is one of the natural processes
that occur during senescence where the skin
will start to loss its elasticity and content of
the collagen. Wrinkles and flabby skin is one
of the results of diminishing collagen
contents [20]. Anti-aging product has
been gained interest among consumers
especially women who are using cream or oral
supplement.
4. ADVANTAGES AND DISADVANTAGES
4.1 Dermal Filler
The most common sources of collagen is cow
and it can be found in the muscle, skin and
tendons. The most common use of bovine
collagen-based dermal filler is Zyderm®and
Zyplast® (Allergan Inc, Santa Barbara,
California, USA).There are some disadvantages
of use of bovine collagen. Specially, to correct
the hand appearance because of the low
longevity, consistency and make the skin to be
uneven [21]. Some adverse reactions were
reported due to the uses of the bovine collagen.
Cases of local cutaneous necrosis were reported
when Zyplast® was injected to the glabellar
region which is the area between the eyebrows
[22]. In addition, Cukier et al., found that there
were nine patients whom developed disease
[23]. According to Klein delayed-type of
hypersensitivity responses were reported during
the use of serum antibodies with collagen. The
diseases are mainly related to types of
inflammation responses that are triggered by the
usage of collagen. Skin test is recommended for
the users if they want to use the bovine collagen
and some authors recommend two skin tests in
interval of two to four weeks due to inflammatory
response and allergic reaction caused by
collagen [24].
There was a research conducted by Park et al.
in 2012, related to iatrogenic retinal artery
occlusion caused by cosmetic facial filler
injections [25]. Study on case of central retinal
artery occlusion caused by collagen injection
at the glabellar region. In addition, Kwon et al.
also reported case of branch retinal artery
occlusion after injection of collagenous filler into
the left anterior nasal septum [26]. Lazzeri et al;
2012 discussed the cases in which scientist
reported cases of blindness as a consequences
of using a bovine cosmetic injections on face
[27].
There is also dermal filler that made out
of natural porcine collagen. This type of
filler can be used for the cosmetic correction
of facial wrinkles and acne scars.
Porcine collagen can stimulate the formation of
new collagen in response to the microtrauma
that was induced by the injection of the filler
[28]. The usage of this type of dermal
filler showed no serious side effect and
also minimal discomfort [27]. Therefore porcine
collagen can be considered to be highly safe as
dermal filler.
Some dermal filler may produce side effects
whereas some will show good result for cosmetic
purposes which depends upon the contents in
the dermal filler.
4.2 Scaffolding
Study was conducted in which researcher’s
combine collagen-based dermal substitute and a
fibrin-based cultured epithelium to replace the
damaged skin of acute wounds. The dermal
substitute is an artificial skin that consist of
silicone sheet at the upper layer, and lower
porous cross-linked bovine collagen with
chondroitin-6-sulfate (glycosaminoglycan) [3,30].
Researchers were able to develop normal skin
on the artificial dermis by 83% of the human
epithelium that grown on the fibrin [31]. In
addition, there were cases reported on positive
long term outcome after using skin substitute
with better formation of the skin structure and low
chance of forming hypertrophic scars [3]. High
cost and intensive care are the two main
concerns with this application. This type of skin
engineering also has successfully been used to
treat patients with chronic wounds such as foot
ulcers due to diabetes and venous leg ulcers
[32]. The time needed for the wound closure is
minimised with high percentage of the successful
wound healing. Somehow, bovine collagen
cannot be used to patient with the allergic
reactions.
New type of skin substitute are developed which
are derived from glycerol are preserved for
human allogeneic skin [33,34]. It also consists of
collagen and elastin fibres. This type of dermal
substitution were used on partial thickness of
burns as temporary biologic dressing and also for
wound bed preparation of excised burns.
Patients that are treated with this type of skin
substitute showed improvement in elasticity of
the skin when it is used together with the skin
graft treatment [35].
When collagen-based scaffold is used, there is a
limitation in elasticity and the scaffold will
contract during the repair process. This
challenge is improvised by the presence of
elastin in the collagen based scaffold to decrease
its stiffness and control the contraction of the
collagen [36]. Collagen-elastin composite type of
scaffold will promote elastin deposition and also
showed good results of cosmetic and
functionality on the patients of burns in total body
surface area (TBSA) of less than 20% [9, 37]. It
also increases the elasticity of the skin and
minimize the contraction of the wound [38].
Another finding for skin substitute is the use of
collagen hydrogel. Collagen hydrogel is
combined with keratinocytes sheet to treat
chronic or acute type of wounds [39]. Major
advantage of this is the ability to deliver cytokine
by dermal fibroblast that will be used to promote
wound healing at the site of injury [40]. The
drawback of this type of materials is its extensive
contraction of the cells that reduce the surface
area after the culture and poor stability of the
skin [41]. It also has poor neovascularisation that
cannot integrate to the host organism [42]. New
blood vessels are important as they will carry
oxygen and feeds the resident cells [13]. Then, it
also has poor mechanical properties and hard to
handle. If it is used as scaffold, it is not resistant
enough to promote cell remodelling and creation
of neodermis; therefore this type of skin
substitute is not accepted as permanent grafting
[14]. Collagen hydrogel is improvised with the
method known as plastic compression [43].
Concentrated collagen hydrogel can stimulate
cell growth and the contraction of the materials is
inhibited due to the higher concentration of the
collagen that helps to improve its stiffness. It also
provides easier handling properties [14].
Neovascularisation was also observed with
complete colonization by the host cells. This
makes the concentrated collagen hydrogel more
suitable as a dermal substitute than the normal
collagen hydrogel.
5. ADVANTAGES AND DISADVANTAGES
OF SKIN CARE PRODUCT
One of the oral supplement of collagen
hydrolysate (CH) where specific collagen peptide
is its composite material [44]. A research study
showed that the supplementation of CH to
fibroblast cultures will increase type I collagen
and proteoglycans with statistically significant
increase of skin elasticity. The skin elasticity
could be improved due to the increase
biosynthesis of dermal matrix macromolecules
[1]. Study also reported that there is no change in
skin hydration, skin roughness and skin
evaporation between CH treatment group and
placebo treatment group. The supplement is
considered as long-lasting effect to dermal as the
effect still can be seen at the end of 4th week
washout phase. The skin elasticity increased up
to 30% will reduce the wrinkles for about 17.7%
[44,45].
However, the effect of product that applied
topically on the skin is different. The effects of
topically used skin care products for anti-wrinkle
was investigated by Xhauflaire-Uhoda et al. [46]
Researchers found that once the treatment of the
topical product is stopped, there were no
evidence of skin miniaturization however low
improvement in skin hydration was observed.
The tested product did not break the skin
barriers. The topical type of product should be
more effective as it encountered superficial
dermis and epidermis part of the skin where it
can be helpful to improve skin elasticity by
increase in epidermal hydration [47].
Ineffectiveness of topical skin care products
could be occur due to the inability of it to
penetrate the structure of skin known as stratum
corneum barrier in order to reach the fibroblast
cell of dermal layer [48]. The stratum corneum is
known as part of the skin that function to
minimize the passive loss of water and prevent
microbial invasion to the body [49,50].
Researchers also found that any raw collagen
materials used topically, will not show desirable
effects to the consumers. A research by Huey-
Jine Chai et al. 2010, investigated the effects on
facial skin qualities with penetration through
transdermal when fish-scale collagen peptide
was used [5]. The result showed that the
collagen peptide was able to penetrate the
stratum corneum to epidermis and dermis in
mice model. The fish scale could be considered
as a choice for source of collagen as scales
composition is rich in collagen, cost effective and
sustainable [10]. Overall, collagen is an important
content of the skin but the route and the way the
collagen-based product applied to the skin is
important.
6. CONCLUSION
Collagen based biomaterials are used in
cosmetic and tissue engineering purposes due to
its biocompatible and biodegradable
characteristics. In cosmetics, collagen can be
used for different purposes such as for dermal
fillers, skin substitute and as facial products. The
use of these biomaterials is good when they are
used as a dermal filler that can stimulate the
formation of new collagen to reduce wrinkles.
Skin substitute can be helpful in the development
of normal skin with good formation and to
promote wound healing. However, there are
some side effects for the uses of collagen in
cosmetics. It can cause inflammatory and allergic
reactions and it may also cause iatrogenic retinal
artery occlusion. For certain application,
intensive care is needed and the cost is very
high. Some collagen products that used as a skin
substitute have a poor formation of new blood
vessels and hard to handle. In conclusion, the
usage of collagen may give good and bad effects
to the users as depends upon many different
factors such as, the purpose of the uses of
collagen, sources of the collagen, location and
application of the collagen etc. The consumers
should be aware about the compatibility of the
product before use to reduce the risk of any side
effects. There are some limitations to use
collagen for cosmetic purposes. Some futuristic
development of use of collagen includes genetic
modification of the transplanted cell and
improvement of the anatomy and physiology of
the skin substitute. This is one of the measure to
improve the process of wound healing and
performance of the skin substitute used to
improve the formation of neovascularisation.
Since, tissue engineered implantation technique
does not have inbuilt capillary network so further
research are needed in this aspects.
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