3.1. Material requirements for biomaterials
Biomaterial by definition is a ‘substance (other than a drug), synthetic or natural, that can be used as a system or part of a system that treats, augments, or replaces any tissue, organ, or function of the body’ . Thus, according to the definition biomaterials are progressively used in tissue engineering. They may be utilized for the construction of implants to replace lost or damaged organs or tissues and may also constitute a scaffold for enhanced stem cells to reconstruct not fully functional tissue [45, 46].
Due to the wide range of potential applications of biomaterials in regenerative medicine, their physical and chemical properties may be different [45, 47]. However, in order to use a biomaterial in medical application, it should follow relevant requirements such as biocompatibility and biofunctionality [45, 47]:
Biocompatibility is the ability to integrate with the recipient’s cells in a safe manner and without adverse side effects.
Biofunctionality is the ability to perform a specific biological function, based on the relevant parameters of the physical and mechanical properties.
Other important properties of biomaterials, which are affecting the potential application in medicine, include [45, 48, 49] the following:
Biodegradation—Decomposition of the material in a natural way, when degradation products remain in the human body but without adverse side effects.
Bioresorbability—Decomposition of the material in a natural way at a certain period of time after implantation. Non‐toxic‐degraded products are removed from the body via metabolic pathways (hydrolytic or enzymatic degradation).
Non‐toxicity—From the surface or porous of the material does not elute any toxic components, such as surfactants, stabilizers, catalysts, pigments and UV absorbents, which were used during production and that are incompatible with living organisms.
Mechanical properties—Biomaterial should possess particular mechanical properties consistent with the anatomical site into which it will be implanted.
3.2. Applications of biomaterials
Several biomaterials useful for distinct applications in medical sciences, including in tissue repair and organ reconstruction, have already been developed over the last few decades [45, 47]. The biomaterial sciences are currently one of the highly advancing fields, which also closely cooperate with biotechnological and medical studies. Recent advancement in regenerative medicine strongly requires such strong support from biomaterial sciences, which may provide novel solutions for tissue repair [4, 49].
Among the biomaterials recognized and developed for potential medical purposes, here are multitude materials commonly present in natural sources or de novo designed and created for such purposes.
3.2.1. Naturally derived biomaterials
Natural materials commonly present in nature such as agarose, collagen, alginate, chitosan, hyaluronate or fibrin fully cooperate with living tissues of the recipient and possess low cytotoxicity [47, 48]. Moreover, they may exhibit specific protein‐binding sites that improve integration with cells after transplantation . Thus, they are considered predominantly interesting for tissue engineering applications.
One of the most common natural biomaterials is collagen—an important component of connective tissue, including bones, tendons, ligaments and skin [46, 50]. Collagen is simply absorbed into the body, is non‐toxic and exhibits a low immune response and as such is a perfect biocompatible material with an adequate mechanical strength and flexibility for several applications. Moreover, collagen enhances cell adhesion to such surface, stimulates also biological interactions between cells and facilitates restoration of the natural microenvironment of cell niche and thereby may support the reconstruction of several damaged tissues [46, 48, 50].
Collagen may be employed for tissue engineering in the form of sponges, gels, hydrogels and sheets. It may also be chemically crosslinked in order to enhance or alter the rate of degradation of the fibres . Currently, collagen preparations are used predominantly in wound healing and cartilage regeneration. Injectable form of collagen is used for cosmetic and aesthetic medicine as a tissue filler. In addition, collagen‐based membranes are used in the periodontal treatment as a barrier preventing the migration of epithelial cells. It also forms a favourable microenvironment for stem cells to facilitate reconstruction of the damaged area [50, 51].
3.2.2. Synthetic biomaterials
Synthetic materials are considered as an alternative to natural materials. Due to their defined chemical composition and the ability to control the mechanical and physical properties, they are extensively used in therapeutic applications and basic biological studies [48, 52–55].
Due to distinct variants of polymerization reaction and formation of co‐polymers, multiple synthetic polymers with wide range of physical and chemical properties may be achieved in chemical laboratories. Moreover, novel technologies in the synthesis and formation of more complex structures allow for the production of advanced composites . Synthetic polymers, such as poly(ethylene) (PE), polyurethanes (PUR), polylactides (PLA) and poly(glycolide) (PGA), are widely employed as implants and components of medical devices . Moreover, polymers may constitute suitable scaffold for cell propagation and enhance their biological activity, including neural stem cells, retinal progenitor cells or smooth muscle cells [55, 57, 58]. Thus, this group of biomaterials is currently in a special focus of scientists working on combined approaches using biocompatible scaffolds and stem cells for tissue repair [55, 57, 58].
Biodegradable polymers, including polyhydroxycarboxylic acids, such as PGA, PLA, poly(3‐hydroxybutyrate), poly(4‐hydroxybutyrate) and poly(∈‐caprolactone) (PCL) are of wide interest in the development of novel technologies . One of their potential applications is utilization in the treatment of cardiovascular diseases. Our recent studies have shown the positive impact of both PCL and PLA scaffolds on proliferation, migration and proangiogenic potential of mesenchymal SCs derived from umbilical cord tissue in vitro, suggesting the possible applications of these materials in cardiovascular repair in vivo (unpublished data) .
Synthetic polymers may also be used in biodegradable stents implanted after a heart attack and greatly contribute to patient recovery . Importantly, the material should have suitable decomposition kinetics. Too long decomposition time (i.e. in the case of PLA or PGA) may lead to late stent thrombosis or blockages [56, 60]. One of a possible solution of this problem is to use rapidly biodegradable polymer stents coated with SCs to help rebuild damaged tissue and additionally stimulate resident cells to grow.
Other types of common synthetic materials useful for biomedical applications are ceramics. It has been well described that ceramic scaffolds, such as, for example, hydroxyapatite (HA) and tri‐calcium phosphate (TCP), are characterized by biocompatibility, high mechanical stiffness (Young’s modulus), very low elasticity and a hard brittle surface . Due to their chemical and structural similarity to the mineral phase of native bone, these materials may enhance osteoblast proliferation and therefore they are widely utilized in bone regeneration [61, 62]. Moreover, ceramics may be exploited in dental and orthopaedic procedures to fill bone defects or as a bioactive coating material for implants to increase their integration after transplantation [63, 64]. However, their clinical applications are still limited due to the difficulties with the ability to change the shape of the material dedicated for transplantation and controlling time of their degradation rate [49, 65].
Similarly, titanium (Ti)‐based metallic materials have been widely optimized for bone repair due to their mechanical properties and resistance to corrosion following the transplantation [66–68]. It has been shown that titanium scaffolds are effectively colonized by osteoblasts responsible for bone formation and this process may be enhanced via additional modifications of the scaffold surface by its roughening, coating with HA or graphene oxide (GO), as well as its biofunctionalization with bioactive molecules such as heparin and bone morphogenetic protein 2 (BMP‐2) [69–72].
Importantly, graphene in its different forms is currently being considered as a potential new promising material for biomedical applications including tissue repair [73, 74]. This 2D carbon biocompatible material exhibits great electrical, conductive and physical properties, which make it interesting for potential applications for drug delivery and scaffold coating in regenerative therapies [74, 75]. It has been shown that graphene may enhance osteogenic differentiation of SCs [72, 73]. Moreover, our recent data also suggest the beneficial impact of graphene oxide (GO) on proliferative capacity, viability and differentiation potential of umbilical cord tissue‐derived MSCs, which confirms the possibility of future graphene employment in tissue repair .
Hydrogels are frequently used biomaterials in the biomedical applications and represent systems consisting of two or more compartments comprising a three‐dimensional (3D) network of polymer chains and water that fills the spaces between the macromolecules [77, 78]. The main characteristics of hydrogels include the biocompatibility and ability to swell in solution until they reach a state of equilibrium. These allow them to be injected into the body in a non‐invasive manner [77, 78].
Hydrogels demonstrate transparency and bioadhesive properties and they are widely used in the pharmaceutical and dermatological industries by local administration or filling the defects caused by injury . They may also be utilized as an injectable material for bone and cartilage tissue engineering, which may be combined with appropriate cell injection [53, 78, 79]. It has been shown that in situ implementation of hydrogels promotes osteoblast differentiation [53, 79]. Therefore, injectable therapy constitutes a promising approach for non‐invasive technique of transplantation, where also cell‐based component may be added to enhance tissue repair.
3.2.4. Smart materials
Smart materials represent a new generation of biomaterials, exceeding the functionality of the currently widely used construction materials. Smart materials are characterized by the ability to alter their physical characteristics in a controlled manner including changing the shape, colour, stiffness or stickiness in response to several external stimuli, such as temperature, hydrostatic pressure, electric and magnetic field or radiation . These changes are related to the revealing or eliciting the new functionality of the material and may be utilized in biomedical applications. Through the common connection between the internal sensor, the activator and a specific control mechanism, smart materials are able to respond to external stimuli. Importantly, these mechanisms are also responsible for the return to the original state, when a stimulant disappeared [80, 81].
Smart materials include several types such as listed below [52, 80, 82–84]:
Colour changing materials—Materials that change colour in a reversible manner, depending on electrical, optical or thermal changes. These types of materials are exploited, for example, in optoelectronic components, lenses, lithium batteries, ferroelectric memory, temperature sensors or as the indicators of battery consumption [80, 81].
Light‐emitting materials—Materials emitting visible or invisible light, as a result of external stimuli such as short wavelength radiation (e.g. X‐rays, ultraviolet light), temperature and electric voltage. They are utilized in electronics, filters for glasses, devices that detect UV rays, in criminology and in geology to identify minerals and rocks. They may also be exploited as a component of protective clothing, safety elements and warning materials [80, 81].
Shape memory materials—Metal alloys that change shape as a result of temperature increase or decrease, respectively, to the set value. The reversibility of the process is to return to its original shape by changing the temperature or under the influence of the applied motion (the effect of pseudoelasticity). These materials are used in temperature sensors, electronics, robotics, telecommunications and production of medical devices (micro‐pump, surgical clamps, orthodontic wire, long‐ and short‐term implants, suture tightening on a stiffen wound, orthopaedic devices, bone nails, clamps, surgical instruments and others) [83, 84].
Self‐assembling materials—Materials that exhibit the intrinsic ability to spontaneously connect individual elements into an ordered 2D or 3D structure. In addition, they can also have the ability to bind metal atoms, ions, molecules or semiconductors. They are widely used in biological research and nanotechnology, that is, in the tissue regeneration, as components for the storage of drugs, crystal engineering, as artificial proteins with pH‐sensitive structure, as semi‐permeable membrane as well as for the production of electronic processors and displays [52, 82].
Self‐repairing materials—Structural damage of this type of material is automatically and autonomously recovered by inducing a change in the shape or the self‐assembly of the molecules. This process is not a method of complete repair of the impaired material; however, it may be used in the military, automotive, aviation and electronics industries [52, 82].