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Abstract(s)
The skin is the largest organ in mammals and acts as a barrier between the human body and
the surrounding environment. It protects the underlying organs and defends the body against
nocive agents.
After an injury, skin integrity is compromised and the organism triggers the wound healing
process for restoring the structure and functions of this organ. Wound healing is an extremely
dynamic and interactive biological process that involves extracellular matrix molecules, soluble
mediators, various resident cells (fibroblasts and keratinocytes) and infiltrating leukocyte
subtypes which, together, act to re-establish the integrity of the damaged tissue and replace
the lost one.
To improve patients odds of survival and to minimize the loss of skin vital functions, this tissue
has to be covered immediately after being damaged. Such highlights the importance of
developing new wound dressings that improve the healing process, making it less painful and,
simultaneously, contributing for the re-establishment of skin structure and functions in a
shorter period of time.
In recent years, various dressings have been developed, using natural or synthetic materials,
for restoring skin native properties and structure. Although, none of them is capable of fully
accomplish this objective.
Taking this into account, the main objective of this work was to develop and characterize skin
substitutes to be used in the treatment of skin disorders. Natural polymers such as agarose,
chitosan and dextran were used for dressings production.
Initially, we evaluated the applicability of a chitosan hydrogel as a wound dressing. The
morphology of the developed system was characterized by scanning electron microscopy while
its cytotoxic profile and degradation by-products were evaluated through in vitro assays. In
vivo experiments were also performed to evaluate the potential of the chitosan hydrogel for
the treatment of skin burns. The results obtained revealed that the hydrogel developed has the
required properties for biomedical application intended, once the in vitro and in vivo assays
revealed that chitosan hydrogel and its degradation by-products are biocompatible and possess
the ability to promote the healing of skin wounds.
In the second study, a dextran hydrogel was loaded with chitosan microparticles containing
epidermal and vascular endothelial growth factors for the improvement of wound healing
process. The hydrogel morphology and cytotoxicity profile and degradation by-products were
characterized by scanning electron microscopy and in vitro assays. Furthermore, in vivo
experiments were also performed to evaluate the applicability of the hydrogel for wound
healing. The results obtained, revealed that the animals treated with this hydrogel showed a
faster wound healing with no signs of local or systemic inflammatory response. Moreover, a
unique application per week of this skin substitute allowed a faster healing than that obtained
when growth factors were topically applied in the wound every two days. Dextran hydrogel proved that it can be used as a wound dressing and also as a carrier of microparticles containing
growth factors involved in wound healing.
In the third study, a thermoresponsive chitosan/agarose hydrogel was produced for being used
in the wound healing process. The porosity, wettability, hydrophilicity, biocompatibility, and
bactericidal activity of the hydrogel were characterized by scanning electron microscopy,
studies of water uptake, determination of contact angle, confocal microscopy, cytotoxic assays,
determination of minimum inhibitory concentration and biofilm deposition, respectively. The
performance of this polymeric matrix in the wound healing process was evaluated through in
vitro and in vivo assays. The attained results revealed that the hydrogel promotes cellular
adhesion and proliferation and also its bactericidal activity. The in vivo studies showed also an
improved healing and the lack of a reactive or a granulomatous inflammatory reaction in the
skin lesions treated with this hydrogel.
During this PhD, various natural polymers were used to produce three different hydrogels,
aimed for wound healing. The in vitro and in vivo assays revealed promising results that may
allow their use as skin substitutes in a near future.
Description
Keywords
Substituto de pele - Caracterização Substituto de pele - Desenvolvimento de revestimento Substituto de pele - Biomateriais Hidrogéis - Revestimento de feridas