Preparation and Properties of Biodegradable Hydrogel-Based Hybrid Wound Dressing

Author:Zhu Zuo

Supervisor:yu jian yong wu de qun


Degree Year:2019





The chronic wound refers to the wound that can not be healed in a short time,even worse,the wound can hardly be healed itself.The healing process includes three stages,that is,inflammation,proliferation and remodeling.During the wound repairing process,microorganisms can easily invade the wound site to form bacterial colonies,leading to serious wound infection.The infection will hinder the wound healing and even cause tissue damage and death.In addition,the proportion of death caused by uncontrolled bleeding accounts for more than 30% of all wound death worldwidely.More than half of death is due to the lack of emergency care.Therefore,rapid control of bleeding is also needed for wound dressings.Hydrogel is a kind of material with three-dimensional(3D)network structure which is similar to the natural extracellular matrix(ECM).Hydrogel-based dressings have the advantages of absorbing exudates,moisture,protecting the wound from bacteria,reducing wound infection and being easy to replace.Morever,the hydrogels can be incorporated into various drugs and growth factors to accelerate the wound healing.For bleeding wounds,hydrogels can be acted as a physical barrier to the bleeding site,contributing to the formation of thrombus and rapid hemostasis.In addition,compared with non-degradable hydrogels,biodegradable hydrogels can be degraded into safe and non-toxic small molecules,causing minimal harm to human body.This type of hydrogel is more in line with the requirements of medical materials.This research mainly includes the following aspects:In recent years,environmental responsive hydrogels,which can change the drug release profile by adjusting the external environment,such as acidity,alkalinity,temperature and ionic strength,have gained more attention in the application of drug controlled release,especially pH-sensitive hydrogels.In this study,a pH-sensitive hydrogel dressing was prepared by peptide based bis-acrylate and acrylic acid(AAc),and triclosan was pre-loaded into the hydrogel to endow the dressing with antibacterial properties.The hydrogel had a low swelling ratio in acidic environment,and drugs were protected inside the hydrogel.When the pH value increased,the hydrogel would swell further,leading to a faster drug release profile.The porous structure of the hydrogel dressing was verified by scanning electron microscopy(SEM).The swelling properties of the hydrogel dressings at different pH environments showed that the hydrogel dressing had pH response activity.The biodegradability of the hydrogel was characterized by SEM and weight loss.The results showed that the hydrogel had good enzymatic degradability.In addition,the drug release and antimicrobial properties of triclosan loaded hydrogel dressings were systematically studied.The drug-loaded hydrogels have the burst drug release behavior of which will cause toxicity and side effects to patients.At the same time,the sustainability of drug effect will be greatly reduced due to the rapid release.The drug release behavior can be controlled more stably by using nano-scale drug carriers.In this study,we constructed hybrid hydrogels with rapid hemostasis and sustainable antibacterial property combining aminoethyl methacrylate hyaluronic acid(HA-AEMA)and methacrylated methoxy polyethylene glycol(mPEG-MA)hybrid hydrogels and chlorhexidine diacetate(CHX)-loaded nanogels.The CHX loaded nanogels(CLNs)were prepared by the enzyme degradation of CHX-loaded lysine-based hydrogels.The HA-AEMA and mPEG-MA hybrid hydrogel loaded with CLNs(labeled as G-1@CLN)displayed a three-dimensional microporous structure and exhibited excellent swelling,mechanical property,and low cytotoxicity.The G-1@CLN hydrogel showed a prolonged release period of CHX over 240 h and the antibacterial property over 10 days.The hemostasis and wound-healing properties were evaluated in vivo using a mouse model.The results showed that hydrogel had the rapid hemostasis capacity and accelerated wound healing.As it is found that the antibiotics have drug resistance,compared with the dressings containing antibiotics,cationic peptides as antibacterial materials have a more durable and broad-spectrum antibacterial activity.Furthermore,the positive charge characteristics of peptides will enhance the interaction with blood cells and platelets through electrostatic interaction,thus inducing blood cell aggregation,platelet activation and coagulation.Surface modification has the advantage of effective contact with wounds.Therefore,direct peptide RRRFRGDK(P3)conjugation to the hydrogel surface through an amidization reaction can enhance the antibacterial and hemostatic abilities with no or minimal outer appearance and inner morphology damage to the original hydrogels.The P3 functionalized hydrogel(H-g-P3)present excellent water uptake capacity,robust mechanical strength,enzymatic biodegradation,good hemocompatibility and cytocompatibility.Moreover,the H-g-P3 hydrogel has better adhesion capacities of blood cell and platelet,and exhibits shorter hemostasis time in mouse-liver injury model.Finally,the wound healing performance is evaluated in vivo using an infected wound model.The results show that Gel-g-P3 hydrogel has accelerated wound healing process.However,hydrogel dressings have obvious defects,that is,lacking tensile mechanical properties,making hydrogels easy to be deformed,or even broken when used as dressings.In this study,the precursor solutions of these above hydrogels were combined with Lyocell nonwoven and cotton fabric,respectively,and the hydrogel/fabric composite dressings were prepared directly by ultraviolet cross-linking method.Hydrogel/fabric composite dressings had good absorption properties,and their tensile breaking strength and elongation at break were greatly improved.In addition,the three composite dressings have excellent water vapor permeability.