Advancements in modification of membrane materials over membrane separation for biomedical applications-Review

Highlights

• The polymer surface modification methods reviewed.

• Compared the surface modification techniques in membrane separation to underlay the current research going in developing new techniques.

• The developed materials in combination of surface modification with high potential as tissue replacements, biosensors and antibacterial materials applications.

• The tailor made membrane modifications for application in drug delivery and other biomedical applications discussed.

Abstract

A comprehensive overview of various modifications carried out on polymeric membranes for biomedical applications has been presented in this review paper. In particular, different methods of carrying out these modifications have been discussed. The uniqueness of the review lies in the sense that it discusses the surface modification techniques traversing the timeline from traditionally well-established technologies to emerging new techniques, thus giving an intuitive understanding of the evolution of surface modification techniques over time. A critical comparison of the advantages and pitfalls of commonly used traditional and emerging surface modification techniques have been discussed. The paper also highlights the tuning of specific properties of polymeric membranes that are critical for their increased applications in the biomedical industry specifically in drug delivery, along with current challenges faced and where the future potential of research in the field of surface modification of membranes.

Introduction

A biomaterial is a substance that is developed to take a form which is used to direct the course of any therapeutic or diagnostic procedure, in medicine by controlling the interactions with components of living systems (Ratner et al., 2012). The list of applications of membranes in the field of biomedicine is endless; some of the most important applications being in diagnostic devices, tissue regeneration, drug delivery, generation of artificial organs or coatings for medical devices, bio-separations, etc., (Mabrouk et al., 2019; Wang et al., 2021). These biomedical applications of membranes require the membranes to satisfy a few important properties, namely, biocompatibility, hydrophilicity and sometimes biodegradability.

The importance of biocompatibility of membrane lies in the fact that the membranes, in interaction with biological fluids, should not stimulate any sort of infection or biological immune responses such as inflammation, coagulation etc. on the cell's host site, and prevent swelling or wear out, on the material side. Most materials, which have desirable mechanical/physical/thermal properties for biomedical applications, are not biocompatible in their pristine form. In biomedical applications, the surface treatment of polymers plays a vital role in targeted synchronized drug release, and improving biocompatibility of the polymers without compromising their bulk characteristics (Yoshida et al., 2013). Surface treatment of polymers has also exhibited superior antibacterial and cytotoxic properties enabling their use in bioengineering. Surface modulated polymer biomaterials have been used in reconstructive medicine for enhanced functionality, improved absorption, and attachment of bioactive compounds to surfaces (Goddard et al., 2007). Applications of these materials in the field of biomedicine demands good biocompatibility which can be achieved in polymer substrates by performing appropriate surface modification processes.

Polymeric membranes are being widely used in biomedicine because of their excellent separation properties at the molecular level and their simple and cost-effective manufacturing processes. They also allow easy surface modification and, hence, help in combining their inherent properties with the specific properties such as enhanced hydrophilicity and biodegradability that are desirable for biomedical applications. For example, in haemodialysis, where the membranes are in constant contact with blood, blood compatibility characterized by reduced blood coagulation, platelet adhesion and protein adsorption are some of the key parameters in choosing a suitable material for the membrane. For instance, polysulfone membrane which possesses good mechanical strength is hydrophobic by nature makes the membranes bioincompatible. When coated with vitamin E, polysulfone membranes reduce oxidative stress, improves blood compatibility and performs better than unmodified polysulfone membrane and, hence, they are used in haemodialysis (Kokubo et al., 2015). It is to be noted that during surface modification changes should be made only at small depth away from the surface and the properties of the modified bulk polymer should remain unaltered (Nedela et al., 2017).

Hydrophilic membranes are preferred for biomedical applications as they improve the flux through the membrane and fouling properties, which in turn makes them more biocompatible and stimuli-responsive (Zhao et al., 2013). The degree of hydrophilicity of membrane controls its protein adsorption which is responsible for flux decline and lowered membrane selectivity (fouling). This, in turn, has its effects on blood purification, blood oxygenation etc (Stamatialis et al., 2008). Several studies have shown that higher the hydrophilicity is, better the biocompatibility is (Xiang et al., 2016; An et al., 2018; Verma et al., 2019).

The biodegradability of a material is defined as the capacity of the material for absorption naturally by the body after disintegration when its function has been accomplished. This property plays a crucial role in drug release by determining the rate of drug release which has to be tailored accurately as a very fast or slow drug release could prove to be ineffective and sometimes (Yadav et al., 2021). Hence, to maximize the efficacy of drug delivery, the unique properties of therapeutic agents such as water solubility, crystallinity, and chemical characteristics need to be captured into appropriate biomedical carriers (Tran and Nguyen, 2017). Two common mechanisms used in biodegradation of polymers include swelling and dissolution by hydrolysis and can be achieved by various methods. For example, the desired rate of biodegradation (hydrolytic) of phosphate buffer solution (PBS) based copolymer consisting of thioether linkages was reported by Fabbri et al. (2015) to have achieved by performing surface modification through of non-thermal plasma surface treatment to the parent homopolymer. It is now evident that surface modifications of membranes are crucial for maximizing the performance and functionalities of the membrane (Mu and Zhao, 2009). From a review of the literature, it seems that the main objectives of the surface modification have been to:

• Curtail undesired interactions like adsorption and membrane fouling that decrease the performance of the membrane. For instance, in most cases, the surface modified PES membranes were found to be more hydrophilic, resulting lower values of protein adsorption (Zhao et al., 2013; Khulbe et al., 2010a, Khulbe et al., 2010b).

• Enhance selectivity where membranes are being used commonly for separation. This is because it is necessary to achieve suitable selectivity for reducing the loss of desirable component and increase the removal of undesired component especially when they have small molecular weights (Nady et al., 2011). For example, in haemodialysis, it is necessary to remove uremic toxins (approximate MW 50kDa) and retain albumin (approximate MW 68 kDa) which is controlled by selectivity of the membrane (Boschetti-De-Fierro et al., 2017).

Popular techniques that are being pursued today for membrane surface modification are blending (Nady and Kandil, 2018), grafting (Kyzioł and Kyzioł, 2018) and plasma initiation (Amani et al., 2019) along with techniques such as enzymatic initiation and chemical patterning (Nady et al., 2011; Kingshott et al., 2011). With the recent advancements in the field of biomedicine and biomaterials developed for specific applications, surface modification of these materials is imperative to enhance the biocompatibility and serve the purpose for which they are truly developed for. Surface modifications are widely applied to modulate or enhance the bio-interactions of biomedical devices and improve other aspects of performance (Buddy et al., 2020). Surface modification is used in the laboratory setting, and also for the treatment of medical devices used in the clinic. Since a medical device may already have appropriate physical properties and be well-understood in the clinic, surface modification provides a means to alter only the bio interactions of the device without the need for redesign, retooling (Ratner et al., 2012). Using various systems such as liposomes, microspheres, polymeric micelles, polymeric nanoparticles, gels etc. which provide promising solution to deliver drugs to achieve the desired therapeutic effect, we have explored briefly on how and why surface modifications are being carried out in the development of drug carriers and how they impact their drug release profiles, targeting, and biocompatibility.

This paper reviews the recent advances and methods of surface modification of polymers, which utilize different techniques to address the diverse needs in the field of biomedicine. In the following sections a detailed novel description along with the mechanisms and comparison of the major surface modification techniques like, grafting, coating, chemical patterning, blending, etc., which are used to enhance applications of polymeric membranes in biomedicine are discussed.