Biocompatibility of hydrogel-based scaffolds for tissue engineering applications

Abstract

Recently, understanding of the extracellular matrix (ECM) has expanded rapidly due to the accessibility of cellular and molecular techniques and the growing potential and value for hydrogels in tissue engineering. The fabrication of hydrogel-based cellular scaffolds for the generation of bioengineered tissues has been based on knowledge of the composition and structure of ECM. Attempts at recreating ECM have used either naturally-derived ECM components or synthetic polymers with structural integrity derived from hydrogels. Due to their increasing use, their biocompatibility has been questioned since the use of these biomaterials needs to be effective and safe. It is not surprising then that the evaluation of biocompatibility of these types of biomaterials for regenerative and tissue engineering applications has been expanded from being primarily investigated in a laboratory setting to being applied in the multi-billion dollar medicinal industry. This review will aid in the improvement of design of non-invasive, smart hydrogels that can be utilized for tissue engineering and other biomedical applications. In this review, the biocompatibility of hydrogels and design criteria for fabricating effective scaffolds are examined. Examples of natural and synthetic hydrogels, their biocompatibility and use in tissue engineering are discussed. The merits and clinical complications of hydrogel scaffold use are also reviewed. The article concludes with a future outlook of the field of biocompatibility within the context of hydrogel-based scaffolds.

Introduction

Tissue engineering, a rapidly evolving field, has changed the therapeutic approach to tissue regeneration and replacement. The recent development of this field stems from reparative medicine in addition to the need for tissues and organs required for transplants. According to the U.S. Department of Health and Services, in 2009 only 28,463 patients received a transplant while over 100,000 patients remained on the waiting list (OPTN/SRTR Annual Report, 2009). Tragically, even after the transplant, patients are treated with immunosuppressants to prevent rejection of the transplanted tissue or organs for the remainder of their lives (Anderson, 2010, Marshall and Browner, 2007). This has led to the conclusion that allotransplantation is only a partial solution (Langer and Vacanti, 1999). The ideal way to circumvent these shortcomings is to use the patient's own cells or a biodegradable material which can promote the ingrowth of neighboring tissues and cells or to serve as a provisional scaffold for transplanted cells to adhere, proliferate, and differentiate within. This strategy is expected to reduce the long waiting time for organ transplants while minimizing the risk of transplant rejection and the necessity for high-risk surgery.

Consequently, this led to the creation of a new branch of research called tissue engineering, first introduced by Langer and Vacanti (Langer and Vacanti, 1993, Russell and Monaco, 1964). This interdisciplinary science arose from the combination of cell and developmental biology, basic medical and veterinary sciences, transplantation science, biomaterials, biophysics and biomechanics, bioimmunology and biomedical engineering (Langer and Vacanti, 1993, Lee et al., 2001). Expertise from these fields combined to undertake the immense task of creating living tissues from only a few cells and combining them with biomaterials such as poly(ethylene glycol)(Viola et al., 2003, Zhu, 2010), collagen (Gorgieva and Kokol, 2011), poly(lactic acid) (Majola et al., 1991) or de-cellularized extracellular matrix (ECM) (Badylak, 2004, Sreejit and Verma, 2013). These biomaterials can be used to compensate for donor shortages and allow patients a faster recovery time with fewer complications, increasing quality of life (Slaughter et al., 2009).

The key characteristic that differentiates biomaterials from other materials is their ability to coexist and interact in the presence of specific tissues or physiological systems such as blood, interstitial fluids, and immune cells and molecules without inflicting an intolerable amount of damage (Tronci, 2010). A key concept in tissue engineering is selecting the proper biomaterial to design and produce an appropriate scaffold which induces no or minimal immune reaction from the recipient. Following recent technological advances and interests for the design and development of engineered biodegradable scaffold systems, tissue engineering has moved into a modern innovative era. Nevertheless, many, or perhaps most, of these bioengineered systems are being challenged mainly due to a lack of adequate data regarding their toxicity and biocompatibility.

Key to understanding biocompatibility is the comprehension of which chemical, biochemical, physiological, physical or other mechanisms are activated by the contact of the biomaterial with the cells in the body and also to understand the consequences of these interactions (Williams, 2008a). Herein, this paper's focus is to collect and review existing knowledge on the biocompatibility of hydrogel-based scaffolds.