Applications of biomaterials in regenerative medicine

Received: March 04, 2019; Accepted: March 18, 2019; Published: March 21, 2019 Biomaterials play a pivotal role in the field of regenerative medicine especially in the replacement of damaged tissues and organs as well as the treatment of chronic diseases to restore normal body function [1,2]. Recent advances in biochemistry, molecular biology, engineering and material sciences have provided wider opportunities for their clinical use. In tissue regeneration, biomaterials usually act as a scaffold to provide the structural support for both cell adhesion and tissue development. They resemble an extracellular matrix (ECM), which is naturally secreted by resident cells to support the surrounding tissues and organs [3]. ECM generally consists of cell adhesion proteins (e.g., laminin and fibronectin), structural proteins (e.g., elastin and collagen), and glycans (e.g., glycosaminoglycans (GAGs) and proteoglycans) [4]. It affords not only spatial organization and physical support, but also a physiological microenvironment that sustains normal cellular functions. Additionally, ECM also contributes to biophysical cues as well as various molecular and signalling events to maintain the cell morphology and phenotype. In response to microenvironmental changes such as mechanical stimuli and all other factors that control the physiological niche (e.g., oxygen and nutrient concentrations), ECM would undergo extensive remodelling [5]. Degradation of the matrix would negatively affect cellular functions including cell growth, survival and differentiation. Therefore, biomaterials have been largely developed to mimic the native structure and composition of ECM and provide structural and functional support to the cells especially for regrowing or regenerating damaged tissues in clinical settings [6].

Biomaterials play a pivotal role in the field of regenerative medicine especially in the replacement of damaged tissues and organs as well as the treatment of chronic diseases to restore normal body function [1,2]. Recent advances in biochemistry, molecular biology, engineering and material sciences have provided wider opportunities for their clinical use. In tissue regeneration, biomaterials usually act as a scaffold to provide the structural support for both cell adhesion and tissue development. They resemble an extracellular matrix (ECM), which is naturally secreted by resident cells to support the surrounding tissues and organs [3]. ECM generally consists of cell adhesion proteins (e.g., laminin and fibronectin), structural proteins (e.g., elastin and collagen), and glycans (e.g., glycosaminoglycans (GAGs) and proteoglycans) [4]. It affords not only spatial organization and physical support, but also a physiological microenvironment that sustains normal cellular functions. Additionally, ECM also contributes to biophysical cues as well as various molecular and signalling events to maintain the cell morphology and phenotype. In response to microenvironmental changes such as mechanical stimuli and all other factors that control the physiological niche (e.g., oxygen and nutrient concentrations), ECM would undergo extensive remodelling [5]. Degradation of the matrix would negatively affect cellular functions including cell growth, survival and differentiation. Therefore, biomaterials have been largely developed to mimic the native structure and composition of ECM and provide structural and functional support to the cells especially for regrowing or regenerating damaged tissues in clinical settings [6].
Natural hydrogels include (i) natural polymers such as chitosan and silk, (ii) ECM proteins such as collagen and elastin, and (iii) ECM originated from various tissues which are subject to decellularization such as dermis, intestinal submucosa and bladder matrix [7]. These materials offer several advantages such as excellent biodegradable and biocompatible, and high flexibility, which possess the capability of changing shape and size to promote the growth of engineered tissue within the surrounding tissues. While most natural hydrogels have attracted much scientific interest due to their inherent outstanding properties, synthetic hydrogels such as polyethylene glycol (PEG) offer more advantages, which include the large-scale production capability and highly tunable physical and mechanical properties, making them significantly useful for 3D cell culturing and tissue engineering [1]. The ability of tuning the properties of hydrogel advances the understanding of interactions between cells and synthetic substrates and recapitulates many of the healthy tissues and disease models. This ability would eventually improve the efficiency of tissue regeneration. Selected commercially available biomaterials are highlighted in Table  1 whereas a number of existing biomaterials for regenerative medicine applications are summarized in Table 2.
To date, multiple challenges are yet to be addressed to translate the existing synthetic biomaterials into practical applications. While being biocompatible, most synthetic hydrogels are synthesized under harsh chemical conditions [8]. The procedures require extra care to ensure that unreacted reagents are ultimately removed to avoid crosscontaminations. Additionally, the capability of some hydrogels to achieve the dynamic and heterogenous nature of the native cellular microenvironment remains elusive [3]. To this end, a variety of manufacturing and processing techniques are being adapted for the synthesis of biomaterials with desirable features and functionality in a safely manner.
Moreover, the use of photochemical reactions to create dynamic microenvironment of hydrogel shows potential in regenerative medicine as these reactions can be conducted in a precise threedimensional space at user-defined time [9]. The spatiotemporal control over chemical reactions can also be performed to achieve optimum functionality of hydrogel [10]. In addition, it is essential to elucidate the molecular pathways between the cells and biomaterials. Studying the mechanism and signalling pathways will review important insights into developing new biomaterials for a more defined cellular response, resulting in a more controlled and efficient tissue regeneration [11].
Even though the structural, mechanical and biochemical properties of native ECM permit the development of new types of tissueengineered constructs, the properties of existing synthetic scaffolds fall short of the criteria for the development of a complex human tissue [12]. This is because of the inability to control all the technical parameters, which limits the study of scaffolds in vivo. In addition, the precise regulation of physiological processes in biomaterials remains a key challenge. It usually includes the process of bioactivation that is normally achieved through the integration of key biomolecules and signals that direct the cells and tissues in vivo [13]. After seeding the cells into hydrogels, the changes in cell behaviour should be monitored periodically in the synthetic microenvironment. The manipulations or signals being introduced should also be tracked while observing the changes in cellular behaviour. In fact, the resulting biomaterials must be both efficacious and cost-effective to be translated into clinical applications. This could lead to an ineluctable dichotomy between the ease and simplicity of scaffold production, and the demand for an appropriate sophistication level by integrating complex yet useful information into scaffold.
More attention should also be paid to the microfabrication technologies that afford an abundance of potential sizes, shapes, porosities, and architectures to create a complex functional engineered tissue or organ for practical use [14]. Integrating the latest biological knowledge and new structural, physical and chemical insights into biomaterials along with a deep understanding of their roles in tissue regeneration are imperative to bridge the gaps in the scientific field. The recent advances in synthetic technology will ultimately yield new generations of multi-functional biomaterials, which could potentially open new approaches in the rapid growing field of regenerative medicine. 14. Yanagawa F, Sugiura S, Kanamori T (2016) Hydrogel microfabrication technology toward three dimensional tissue engineering. Regen Ther 3: 45-57.