Lipase mediated functionalization of poly (3-hydroxybutyrate-co-3-hydroxyvalerate) with ascorbic acid into an antioxidant active biomaterial Shashi Kant Bhatia a,b , Puneet Wadhwa c , Ju Won Hong a , Yoon Gi Hong a , Jong-Min Jeon a , Eui Seok Lee c , Yung-Hun Yang a,b, ⁎ a Department of Biological Engineering, College of Engineering, Konkuk University, Seoul 05029, South Korea b Institute for Ubiquitous Information Technology and Applications (CBRU), Konkuk University, Seoul 05029, South Korea c Department of Oral and Maxillofacial Surgery, Korea University Guro Hospital, Seoul, South Korea abstract article info Article history: Received 30 July 2018 Received in revised form 6 November 2018 Accepted 10 November 2018 Available online 11 November 2018 Naturally produced polyhydroxyalkanoates (PHAs) biopolymers have limited medical applications due to their brittle and hydrophobic nature. In this study poly(3-hydroxybutyrate-co-3-hydroxyvalerate) P(3HB-co-3HV) co- polymer was produced using engineered Escherichia coli YJ101, and further functionalized with ascorbic acid using Candida antarctica lipase B mediated esterification. Copolymer P(3HB-co-3HV)-ascorbic acid showed lower degree of crystallinity (9.96%), higher thermal degradation temperature (294.97 °C) and hydrophilicity (68°) as compared to P(3HB-co-3HV). Further, P(3HB-co-3HV)-ascorbic acid biomaterial showed 14% scavenging effect on 1,1-diphenyl-2-picryl-hydrazyl (DPPH), and 1.6 fold increase in biodegradability as compared to P(3HB- co-3HV). Improvement of PHAs polymer properties by adding functional groups could be a good approach to in- crease their biodegradability, economic value and important applications in the medical field. © 2018 Published by Elsevier B.V. Keywords: Antioxidant Biomaterial Copolymer Esterification Polyhydroxyalkanoates 1. Introduction Polyhydroxyalkanoates (PHAs) are biopolymers produced by vari- ous microbes under nutrient-starved conditions [1–5]. PHAs have dif- ferent applications in tissue engineering, drug delivery and packaging [6–9]. Poly(3-hydroxybutyrate) P(3HB) is the most commonly pro- duced and best characterized member of PHAs, but has limited applica- tions due to its high melting point, rigidness and brittle nature [10–12]. To improve properties of PHAs, researchers are working on synthesis of 3HB-based copolymers e.g. poly(3-hydroxybutyrate-co-3- hydroxyvalerate) P(3HB-co-3HV), poly(3-hydroxybutyrate-co-4- hydroxybutyrate) P(3HB-co-4HB), and poly(3-hydroxybutyrate-co-3- hydroxyhexanoate) P(3HB-co-HHx) etc. [10,13–17]. Incorporation of other monomers to P(3HB) may change its properties and resulted co- polymers have less stiffness, higher elongation to break and reduced melting point [16]. Copolymer P(3HB-co-3HV) has been reported as an attractive polymer because of its improved physical properties [18,19]. Despite of change in physical properties of PHAs by incorporation of different subunits, copolymers exhibit slow degradability, resorbability due to intrinsic hydrophobic properties that restrict cell-colonization. Most of the biomaterials used in tissue engineering are incompatible and cause inflammatory response due to oxidative stress [20]. As a re- sult leukocytes release various cytokines, chemokines and generate var- ious reactive oxygen species (ROS) e.g., superoxide, hydroxyl radicals and hydrogen peroxide [21]. These ROS further affect the normal func- tion of cells by damaging DNA, proteins and lipids. Indeed, the detection of ROS is currently being used to characterize the compatibility of bio- materials, both in vitro and in vivo [22]. As excess of ROS is a significant cause of toxicity of many biodegradable materials in medical applica- tions. Therefore, to counter the effects of oxidative stress and inhibit ex- cessive ROS generation there is a need to prepare biomaterials have antioxidant properties. Ascorbic acid a strong antioxidant, used here to develop functional copolymer P(3HB-co-3HV). Biodegradability of the PHA copolymer is other limitation, as their surface is quite inert, hy- drophobic, and has no physiological activity [23]. The surface modifica- tion of copolymer appears a real challenge for improving adhesion and to make the polymer more biodegradable. The cell adhesion capability of copolymer can be improved by the introduction of functional groups by chemical modification. Various chemical methods have been re- ported for functionalization of PHAs i.e., hydroxylation, carboxylation, epoxidation and chlorination etc. [24]. Yu et al. prepared graft polymer of P(3HB-co-3HV) with hydrophilic polyacrylamide (PAM) and re- ported that PAM helps to guide chondrocytes spreading and formation International Journal of Biological Macromolecules 123 (2019) 117–123 ⁎ Corresponding author at: Department of Biological Engineering, College of Engineering, Konkuk University, Seoul 05029, South Korea. E-mail address: seokor@konkuk.ac.kr (Y.-H. Yang). https://doi.org/10.1016/j.ijbiomac.2018.11.052 0141-8130/© 2018 Published by Elsevier B.V. Contents lists available at ScienceDirect International Journal of Biological Macromolecules journal homepage: http://www.elsevier.com/locate/ijbiomac