Biocompatibility of silver / poly(vinyl alcohol) / graphen nanocomposite hydrogels in rat subcutaneous tissues for biomedical applications

Abstract

This doctoral dissertation was designed in order to test the biocompatibility of two newly synthesized and previously in vitro characterized hydrogels based on poly(vinyl alcohol) polymers - Ag/PVA and Ag/PVA/Gr, which are intended for making wound dressings or soft tissue implants tissue. Poly(vinyl alcohol) (PVA) is a synthetic polymer commonly used in biomedicine due to its non-toxicity, solubility, biocompatibility, elasticity and the ability to produce reversible hydrogels with high sorption capacity. In the last few years, research has also focused on the incorporation of graphene (Gr) into hydrogel PVAs, in order to improve their mechanical strength and durability. In tissue engineering and regenerative medicine, it is particularly important that implants and bandages contain an antiinflammatory and antibacterial active ingredient to protect the sterility of the wound, or to prevent infection in the implant surrounding tissue. It is known that silver nanoparticles (AgNPs) have excellent antibacterial activity and are therefore often used as an active component of PVA-based hydrogel biomaterials. In order to test the biocompatibility of newly synthesized hydrogels, the soft tissue response to deep subcutaneously implanted Ag/PVA and Ag/PVA/Gr implants was compared to the reaction to the commercial calcium-alginate wound pad (Suprasorb ©, Lohmann & Rauscher GmbH & Co. KG, Neuwied, Germany), which is implanted in an identical manner. The tissue irritation index (IrI) was evaluated as the basic measure of tissue response to implanted hydrogels. In order to determine the degree of biocompatibility, the thickness of the connective tissue capsule around the implanted hydrogels, the number of inflammatory cells, including the Langerhans giant cells, the number of macrophages in the perimplant zone and their eneventual migration to the biomaterial, as well as the number of blood vessels around the implantation zone, were measured. The ratio of proliferating and apoptotic cellular skin and subcutaneous tissue cellular entities was observed, due to their responsibility for regeneration and reparation processes...

Ova doktorska disertacija dizajnirana je u cilju da se ispita biokompatibilnost dva novosintetisana i prethodno in vitro okarakterisana hidrogela na bazi sintetskog polimera polivinil-alkohola − Ag/PVA i Ag/PVA/Gr, koji su namenjeni za izradu obloga za rane ili za implantate za meka tkiva. Polivinil-alkohol (PVA) je sintetički polimer koji se često koristi u biomedicini zbog svoje netoksičnosti, rastvorljivosti, biokompatibilnosti, elastičnosti i sposobnosti stvaranja reverzibilnih hidrogelova s visokom sposobnošću sorpcije. U poslednjih nekoliko godina, istraživanja se takođe fokusiraju na ugradnju grafena (Gr) u hidrogelove PVA kako bi se poboljšala njihova mehanička čvrstoća i trajnost. U inženjerstvu tkiva i regenerativnoj medicini posebno je važno da implantati i zavoji sadrže antiinflamatornu i antibakterijsku aktivnu komponentu kako bi zaštitili sterilnost rane ili sprečili infekciju u tkivu koje okružuje implantat. Poznato je da nanočestice srebra (eng. silver nanoparticles, AgNPs) poseduju odličnu antibakterijsku aktivnost, pa se zbog toga često koriste kao aktivna komponenta biomaterijala na bazi hidrogela od PVA. U cilju ispitivanja biokompatibilnosti novosintetisanih hidrogelova, praćena je reakcija mekog tkiva na duboko potkožno postavljene implantate od Ag/PVA i Ag/PVA/Gr i poređena je sa reakcijom na komercijalnu oblogu za rane na bazi kalcijum-alginata (Suprasorb©, Lohmann & Rauscher GmbH & Co. KG, Neuwied, Germany), koja je implantirana na identičan način. Procenjivan je tkivni iritacioni indeks (IrI) kao osnovna mera tkivnog odgovora na implantirane hidrogelove. Za određivanje stepena biokompatibilnosti merena je debljina vezivnotkivne kapsule oko implantiranih hidrogelova, broj inflamatornih ćelija, uključujući i Langerhansove džinovske ćelije, broj makrofaga u periimplantnoj zoni i njihova enevntualna migracija u biomaterijal, kao i brojnost krvnih sudova mikrovaskularnog korita oko zone implantacije. Posmatran je odnos proliferacije i apoptoze ćelijskih entiteta kože i potkožnog tkiva odgovornih za procese regeneracije i reparacije...