POLY(ETHYLENE) OXIDE SYNTHETIC POLYMER HYDROGELS FOR MEDICAL APPLICATIONS

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1 POLY(ETHYLENE) OXIDE SYNTHETIC POLYMER HYDROGELS FOR MEDICAL APPLICATIONS Haryanto University of Muhammadiyah Purwokerto, Indonesia ABSTRACT Recently, syntheticpolymer hydrogels have emerged as a promising biomaterial for biomedical applications because of their biocompatibility, water absorption capability, degradability and better mechanical properties than natural polymer hydrogels. Therefore,the current study was undertaken with the main objective of developing modified poly(ethylene oxide) (PEO) hydrogel films with poly(ethylene glycol) diacrylate (PEGDA), poly(ethylene glycol) dicarboxcylate (PEGDC), poly(ethylene glycol) dimethacrylate (PEGDMA) and hyperbranchpolyglycidol (HPG) with enhancedproperties using electron beam (E -Beam) for three major applications namely wound dressing, anti-adhesion barrier and tissue engineering scaffold. Crosslinked PEGDA/PEO hydrogel was developed for wound dressing application. Thecross-linked PEGDC/PEO and PEGDMA/PEO hydrogels were developed for an anti-adhesion barrier application.and a microporous hydrogel scaffold was developed from HPGand PEO using e-beam induced cross-linking for tissue engineering applications.this study shows the potential ofmodified PEO hydrogel films in biomedical applications especially as wound dressing, anti-adhesion barrier and tissue engineering scaffold. Keywords: crosslinkedhydrogel,e-beam, poly(ethylene) oxide, electron beam,biomedical applications. INTRODUCTION One of the most promising class of biomaterials seem to be hydrogels. The word biomaterial is generally used to recognize materials for biomedical applications. For over thirty years hydrogels have been used in numerous biomedical applications such as drug delivery, cell carriers, wound dressing, tissue engineering scaffold, contact lenses, anti-adhesion barrier and absorbable sutures as well as in many other areas of clinical practice. Hydrogels are polymeric networkswhich have the ability to absorb and hold water from 10 20% (an arbitrary lowerlimit) up to thousands of times their dry weight within the spaces available among the polymeric chains. As the term network implies, crosslinks have to be present to avoid dissolution of hydrophilic polymer chains/segments into the aqueous phase. Hydrogels may be chemically stable or theymay degrade and eventually disintegrate and dissolve [1,2]. The water holding capacity of the hydrogels arise mainly due to the presence of hydrophilic groups, viz. amino, carboxyl and hydroxyl groups, in the polymer chains.higher the number of the hydrophilic groups, higher is the water holding capacity while with an increase in the crosslinking density there is a decrease in the equilibrium swelling due to the decrease in the hydrophilic groups. As the crosslinking density increases, there is a subsequent increase in the hydrophobicity and a corresponding decrease in the stretchability of the polymer network. As mentioned above, hydrogels are crosslinked polymeric networks and hence provide the hydrogel with a 3-dimensional polymeric network structure [3]. The water holding capacity and permeability are the most important characteristic featuresof a hydrogel. The disintegration and/ordissolution could happenedif the network chain or cross-links are 2

2 degradable [4]. The Biodegradable hydrogelscontaining labile bonds, therefore advantageous in applications such as tissueengineering, wound healing and drug delivery.the labile bonds canbe broken under physiological conditions either enzymatically or chemically, in most of thecases by hydrolysis [5,6].Biocompatibility is the third most important characteristic property required by thehydrogel. Biocompatibility calls for compatibility with the immune system of the hydrogeland its degradation products formed, which also should not be toxic.generally, hydrogels possess a good biocompatibility since their hydrophilic surface has alow interfacial free energy when in contact with body fluids, which results in a lowtendency for proteins and cells to adhere to these surfaces. Moreover, the soft and rubberynature of hydrogels minimises irritation to surrounding tissue [7]. In this study, we prove the possibility to develop the facile fabrication of the remarkable modified PEO crosslinked hydrogel film which fullfilled the ideal properties of biomaterial in particular biomedical applications such as wound dressing, anti-adhesion barrier and tissue engineering scaffold using electron beam. EXPERIMENTAL PEO and additive polymer ( PEGDA, PEGDC/PEGDMA, HPG)were used for preparation of the hydrogel films.aqueous solution of additive polymer/peo (5% w/w)was prepared by stirring the solution at room temperature for 24 hours. The solution was made with variouscomposition. The calculated amount of aqueous solution was poured into a petri dish to formdry additive polymer/peo film with a thickness of 0.3 mm for wound dressing and 0.1 mm for anti-adhesion barrier and scaffolds. The solution was dried in the oven at 55 C for 24 hours,and thenremaining moisturewas removed in a vacuum oven for 6 hours at the same temperature. Dry hydrogel films were sealed in an evacuated polyethylene bag, followed by irradiation at 300 kgy using an EB having a beam current of 5 ma and 10 ma with an energy of 0.7 MeV generated from an EB Accelerator. Various parameters were tested for each applications ( wound dressing, anti-adhesion barrier, scaffolds). RESULTS AND DISCUSSION For wound dressing applications, the results indicated that higher content of PEGDA could enhance crosslinking of hydrogel in which high cross linked structure could not sustain much water within the gel structure. It can be seen from fig 1 that the tensile strength of PEO/PEGDA blend hydrogel increased steadily with increasing PEGDA content and reached the maximum point at 0.48 MPa with 10% PEGDA. The water vapor transmission rate of PEO/PEGDA hydrogel was 19 g/m 2 h. The result indicates that the hydrogel could keep moist environment on the interface between the wound and dressing speeding up the healing process. The invivoresult (Fig 2.)showed that a significant reduction of wound size was observed with the hydrogels compared to controlled group after 3 days of post operation. 3

3 Fig 1.Fig 2. In anti-adhesion barrier application, the results showed that 10% PEGDC hydrogel exhibits (Fig 3.) the superlative mechanical strength with the highest elongation at break (69.33 ± 6.87 %). It is also shows the lowest hemolysis activity (6.03± 0.01%) and the highest tissue adherence( Fig 4.) that ensure the film was easily placed onto tissue with good adherence during the wound healing process. The efficacy of 10% PEGDC/PEO cross-linked hydrogel as a barrier for reducing post surgical adhesions was evaluated using a rat cecum model. 4

4 Purwokerto, 28 November 2015, ISBN Fig 3. Fig 4. Moreover, in tissue engineering scaffolds application, the microporous HPG/PEO hydrogel scaffold was successfully developed using a simple e-beam irradiation (Fig 5).The in vitro cytotoxicity results demonstrated that HPG/PEO hydrogel scaffolds exhibited good cell viability and low cytotoxicity, as expected from the materials. Fig 5. CONCLUSION Thedevelopment of modified poly(ethylene oxide) (PEO) hydrogel films with PEGDA,PEGDC, and HPGwas successfully producedd with improvedproperties using electron beam (E-Beam) for three major applications namely wound dressing, anti-adhesion barrier and tissue engineering scaffold. REFERENCES [1] D. Campoccia, P. Doherty, M. Radice, P. Brun, G. Abatangelo, D.F. Williams, Semi Synthetic ResorbableMaterials from HyaluronanEsterification, Biomaterials 19 (1998) [2] G.D. Prestwich, D.M. Marecak, J.F. Marecak, K.P. Ver- cruysse, M.R. Ziebell, Controlled Chemical Modification of Hyaluronic Acid, J. Controlled Release 53 (1998)

5 [3] K. Pal, A.K. Banthia and D.K. Majumdar, Polymeric Hydrogels: Characterization and Biomedical Applications A mini review, Designed Monomer and Polymers 12 (2009), [4] S.K.H. Gulrez, S. Al-Assaf, G.O. Phillips, Hydrogels: Methods of Preparation, Characterisation and Applications, in: A. Carpi (Eds), Progress in Molecular and Environmenta l Bioengineering - From Analysis and Modeling to Technology Applications, InTech., United Kingdom, 2011, [5] W.E. Hennink, C.F. van Nostrum, Novel Crosslinking to Design Hydrogel, Adv. Drug Deliv. Rev. 54 (2002) [6] A.S. Hoffman, Hydrogels for Biomedicals Applications, Adv. Drug Deliv. Rev. 54 (2002) [7] J.M. Anderson, J.J. Langone, Issues and Perspectives on the Biocompatibility and Immunotoxicity Evaluation of Implanted Controlled Release Systems, J Control Release. 57 (1999)