Marine-Derived Biomaterials for Tissue Engineering Applications

Biomaterials with functional properties are used to fabricate scaffolds for bone tissue engineering. Several of these materials can be derived from nature, processed and transformed into regenerative scaffolds and/or artificial matrices for applications in bone tissue repair or regeneration. In this chapter, we discuss the basic biology of bone development and the utilization of chitosan, hydroxyapatite and diatoms for BTE. The regenerative properties of Chitosan are desirable due to its close proximity with glycosaminoglycan—an extracellular matrix polysaccharide, which interacts with collagen fibers. Nano-hydroxyapatite is an inorganic component of natural bone matrix with osteoinductive properties. Diatoms are important source of biogenic silica and their high surface area, as well as nanoscopic pore structure make them desirable for delivery of biomolecules and reinforcing structural functions of three-dimensional scaffold matrices. Additionally, we discussed the methods used to fabricate the scaffolds for bone repair.

Marine organisms possess a vast range of properties, which portray a lot of their appropriate biomedical application potentials either directly, modified or as templates for biomimicking. It is and will remain a humble and smart move to learn from nature and try to copy faithfully the vital components so as to develop implantable biomaterials to mimic efficiently natural tissues or organs in order to substitute effectively diseased tissues or organs, to stimulate the body’s own regenerative mechanisms, and eventually to promote tissue healing. The potentials of marine materials in tissue engineering and regenerative medicine applications are now evident. Recent advances in this area have shown to improve people’s life.

Processes such as traditional wet chemical methods and heat and pressure-based hydrothermal methods are some of the important methods that has been used to produce hydroxyapatite (HAp), tricalcium phosphate (TCP) and other phosphate derivatives. Recently, new approaches such as ultrasonication (can be considered as a mechanical processing route) and hot-plating (heating element added to mechanical processing) were introduced. Using these new approaches, production for nanostructured calcium phosphate can be easily achieved. Traditionally, calcium phosphate-based compounds are produced using starting materials that contains calcium and phosphate. However, the use of marine structures as raw ingredients has been widely encouraged and their uses in the medical/surgical arena are creating new avenues such as in applications that support bone repair and regeneration. Primary sources of marine-based materials are numerous and includes corals, algae, cuttlefish, fish bones, sea urchin, sea snail shells, sponges, sea shells, foraminifera, barnacles, nacre, sea mussels and so on. Knowing other chapters in this book covers the review of these materials in more detail, therefore in this chapter, we aimed to give examples and review some of the new as well as traditional production routes and techniques used to characterize the physiochemical properties of the calcium phosphates produced are also examined.

The materials that are developed from the different kind of marine organisms have a broad range of properties and characteristics that can explain their potential functions in the biomedical area. Accordingly, new opportunities are created by biomaterials produced from marine-based sources such as calcium phosphate-based bioceramics, composites, and polymers within the biomedical fields such as new drug delivery systems, the design of novel implantable devices, and various applications in tissue engineering. The major aim of this chapter is to explain the importance of marine structures applicable for biomedical applications as well as choosing the appropriate conversion technique in order to obtain designs and structures best suited for their intended use. Therefore, we will highlight various conversion techniques used in the synthesis of calcium phosphate bioceramics from various marine sources such as Tubipora musica, Foraminifera, Porites Hard Corals and Halimeda cylindracea calcified algae, and their biomedical applications in this chapter.

Chitosan is a marine polymer, which possesses numerous favorable properties including bioadhesivity, biodegradability and biocompatibility, which have enabled its use in drug delivery and tissue engineering. Furthermore, chitosan has been widely investigated in vitro and in vivo for its bioactive properties such as anti-inflammatory, antimicrobial, hemostatic, wound healing etc. This chapter will comprehensively detail the promising characteristics of chitosan as a biomaterial for drug delivery and tissue engineering, with regard to its safety, quality and efficacy, and review the recent advances on its applications in dentistry.

An increase in life expectancy due to improvements in healthcare, in parallel with high percentage of injures, because of traffic accidents and sport activities, has emerged as the primary reasons for the replacements of lost, infected, and damaged bones. Combined with tissue engineering, this is an area of great interest to regenerative medicine. Novel scaffolds development, providing a suitable environment that can favor osteoinduction for the newly formed bone is needed. Composite porous hydrogels, based on alginate and chitosan with the dispersed phase from powders of bioceramics, such as hydroxyapatite (HAp), are recently developed for this reason. This work presents a reverse and novel approach, where these two popular hydrogels are infiltrated in a 3D HAp-scaffold. More specifically, HAp is obtained from aragonite from cuttlefish bone via hydrothermal transformation. This reinforcement of HAp with alginate or chitosan hydrogels, through infiltration method gives to the final product proper mechanical potential for hard tissue regeneration. The structure of the produced scaffolds resembles the microstructure and the texture of the natural bone. These advanced scaffolds are easily handled by the surgeon while maintaining their porous structure during the implantation process to promote the regeneration of newly formed bone tissue. In particular, once such a scaffold is implanted in an area where the bone tissue is lost, biological liquids will be able to penetrate into the pores of the lyophilized composite scaffold. The polymeric matrix will then be dissolved and the remaining HAp, or its precursor compounds, which will eventually transform into HAp, will promote osteoinduction. The worldwide availability and the low cost of cuttlefish bone, along with their biological-natural origin are attractive features making them highly sorted material used in the preparation of advanced scaffolds containing HAp for applications in biomedicine. The optimization of the fabrication technique is required to unravel the endless potential of biomaterials, shedding light on this promising interdisciplinary field, which includes both tissue engineering and drug delivery system approaches.

The current need for new medicines with reduced toxicity, enhanced bioavailability as well as improved drug efficacy and patient compliance is more pressing than ever before. Clinical active agents can now be reformulated with the help of nanotechnology into “nanopharmaceuticals” with superior pharmacokinetics for site-specific delivery. With the available nanotechnology, studies suggested that marine drugs hold tremendous promise to bring forth novel medicines for the treatment of a wide range of human diseases, but unfortunately this promise has yet to be fully realized. Deadliest diseases such as cancer, HIV/AIDS, and neurological disorders, just to mention few, can be halted by using marine nanopharmaceuticals, which are cost-effective natural products. Legal and scientific frameworks have to be in place with full support from global human health communities to create a unique set of opportunities in the cause of biodiscovery and marine drug development processes.

The world’s oceans represent an enormous resource for the discovery of potential therapeutic agents. During the last decades, numerous novel compounds have been isolated from marine organisms and many of them have been applied for phamacological industry. Notably, marine algae are known to be one of the most important producers of variety of chemically active metabolites. Among them, phlorotannins, a polyphenol from brown algae, have been revealed to possess numerous biological activities such as UV-protective, anti-oxidant, anti-viral anti-allergic, anti-cancer, anti-inflammatory, anti-diabetes, and anti-obesity activities. Therefore, phlorotannins are considered as promising agents for the development of pharmaceuticals. This contribution focuses on phlorotannins from brown algae and presents an overview of their biological activities and health benefit effects.

The ultimate goal of tissue engineering is to regenerate and/or replace fully functional tissue, or to stimulate the body to regenerate its own fully functional tissue (Vacanti and Langer in Lancet 354:SI32–SI34, 1999). This technology is of particular use in orthopaedics where various reconstructive operations are conducted throughout the musculoskeletal system. Many tissue engineering techniques utilize specific combinations of living cells, manufactured macromolecular biomaterials (matrices), and bioactive factors (cytokines and/or growth factors) to direct synthesis and organization of tissues (Fodor in Reproductive Biology and Endocrinology 1:102, 2003). The architecture and biochemical nature of matrices is a key aspect of cell-based tissue engineering. The matrix provides a vehicle for delivery of stem cells and progenitors to a desired site, and provides surfaces that facilitate the attachment, survival, migration, proliferation and differentiation of these cells. The ideal scaffold requirements for bone tissue engineering include biocompatibility, osteoconductive or osteoinductive capacity, high porosity that enables nutrient transport, infiltration of cells, degradability over suitable time scales, and interstitial flow of fluid (Bruder and Fox in Clinical Orthopaedics and Related Research 367:S68–83, 1999). The skeletons of Porifera appear to have unique properties that may provide for potential bioscaffolds in cell-based bone tissue engineering. These properties include the collagenous composition of the fiber skeleton, its ability to hydrate to a high degree, and the possession of open interconnected channels created by the fiber network (Green et al. in Tissue Engineering 9:1159–1166, 2003). In addition to this, the phylum has a tremendous diversity of skeletal architecture within the 8000 extant species currently described, many of which are readily available for use (Hooper and Van Soest in Systema Porifera: a guide to the classification of sponges. Academic/Plenum, New York, 2002).

Chitin as a biological material which has been identified in skeletal structures of a broad variety of unicellular (yeast, protists, diatoms) and multicellular (sponges, corals, worms, molluscs, arthropods) organisms is recognized as natural template with good perspectives in modern biomedicine. This chapter provides first insights into prospective applications of naturally prefabricated three-dimensional chitinous scaffolds from selected marine sponges in tissue engineering. This became possible only owing to the recent discovery of poriferan chitin which provoked renewed multidisciplinary interest driven by growing demand in novel biomimetic materials. Here, we focused on both demosponges of Verongiida order as a renewable source of chitin scaffolds with jewelry designs, and human mesenchymal stromal cells having high therapeutic potential. The chapter covers approaches for isolation of scaffolds from the chitin-bearing marine sponges, nuances of their interaction with human cells and cryopreservation potential.

This chapter examines the sea urchin ligament as a potential decellularized bioscaffold by discussing the significance of collagen fibrils, which are highly-paralleled slender structures embedded in the hydrated proteoglycan-rich (PG) extra-cellular matrix (ECM) of tendons, for reinforcing the soft connective tissue. The discussion is presented in two parts as follows. Part one examines the role of collagen fibrils for providing structural support for the tissue, in the context of the structure of the collagen fibril, and mechanics of stress transfer in the tissue. Part two will review the potential clinical applications of the decellularized bioscaffold, related to tissue implants for repair and regeneration.

The use of advance technology allocated a scientific community with significant development in the field of tissue engineering and medical sciences. Developing a biomaterial to replace the diseased or damaged tissue is a paramount importance for an effective regenerative approach, so that the original structural and functional status is recovered. Due to its rich biodiversity, marine environment yields immense potential and offer various organisms from which promising natural substances can be isolated to mimic the tissue ECM (extracellular matrix) in the body. Findings by various researchers both in vitro and in vivo also support the opinion that the derived structures from aquatic origin have optimistic potential for biomedical application. In this chapter, we shall discuss some of the marine-derived biomaterials which can be employed for various tissue engineering approaches. Marine ecosystem nourished a wide variety of creatures like corals, seashells and sea urchins from which various biopolymers can be extracted. These bio-molecules offer a new dimension for clinical application in dentistry, oral and maxillofacial surgery, wound healing, local drug delivery system, cartilage and bone tissue engineering. As the substances derived from marine origin are organic in nature, they are usually non-toxic, biocompatible, bioactive and well tolerated by the body, which boost their efficacy for tissue engineering application.

In recent years, a striking development has been achieved in marine biomaterials for bone tissue repair. Marine sources have proven to be non-polluting and versatile for biomedical applications. Bone tissue engineering is a promising alternative for treating bone ailments caused due to trauma and surgical intrusions. Biocomposites comprise of biodegradable and biocompatible materials and mimic the architecture of bone and support regeneration. Significant sources of marine biomaterials are fish, invertebrates, fungi, corals, etc. Bone defects are treated using marine biocomposite polymers such as chitosan, collagen, alginate, gelatin, and ceramics. Chitosan is anti-microbial and bioactive; hydroxyapatite and collagen are significant constituents of bone, and alginate boosts mechanical strength and structural integrity of biocomposites. This chapter accounts for the source and types of biomaterials from marine fauna, the fabrication of biomaterials as scaffolds and their biological activity in enhancing bone repair in vitro and in vivo.

Extensive research has been conducted on hydroxyapatite as a bone tissue engineering scaffold due to its low toxicity, biocompatibility, bioactivity and chemical similarity to bone. Hard coral species as well as red and green calcified marine algae have naturally porous skeletons that resemble cancellous bone. Under controlled hydrothermal conditions, these materials can be converted to hydroxyapatite with their porosity and interconnectivity preserved. The availability of hard coral species is limited due to the damage caused by harvesting procedures and decline in coral reefs. As an alternative, hydroxyapatite can be produced from red and green algae species. Currently, red algae derived Algipore® grafts are commercially available for maxillary sinus bone augmentation. Long term clinical studies have confirmed the bone regenerating capabilities of Algipore® when mixed with autologous bone debris and blood, but research on the use of Algipore® tissue scaffolds seeded with mesenchymal stem cells is still ongoing. This chapter reviews the synthesis of hydroxyapatite derived from marine algae and gives background to clinical studies as well as the characterisation techniques used to analyse these materials.

Natural biomaterials derived from marine sources are gaining attention in the field of bone tissue engineering owing to their biodegradability, biocompatibility, bioactivity, and structural similarity with the natural bone extracellular matrix. They recapitulate bone microenvironment and components of natural bone tissue which augments treating critical-sized bone defects. Negating the necessity of revision surgeries due to its biodegradable nature, marine biomaterials based biocomposite scaffolds provides various advantages over the conventional routes of employing metallic implants for bone tissue repair and regeneration. Marine biota provides renewable resources for isolation of biopolymers such as chitosan, alginate, collagen, fucoidan and hydroxyapatite bioceramics that are widely explored for its biomimetic properties in bone tissue engineering. In this chapter, we explore the role of composites fabricated using biomaterials isolated from the marine source, especially chitosan for bone tissue regeneration.

Natural polysaccharides of marine origin are gaining interest in biomedical applications. Seaweeds are most abundant source of polysaccharides, as alginates, agar and agarose as well as Carrageenans. Even cellulose and amylose have been extracted from the macroalgae. Chitin and chitosan are derived from the exoskeleton of marine crustaceans. Interdisciplinary fields involving various science and technology aspects such as cell sciences, biomaterials, medical sciences and engineering are referred to as tissue engineering, which is an upcoming new field intended to replace biological functions in human body. Tissue engineered scaffolds and artificial organs developed by such technique has replace injured parts in human body. Technological advancements have made it possible to obtain active ingredient in marine organisms by controlling the growth and isolation conditions. Present review has focused on progress in discovering and producing new applications of marine polysaccharides in biomedical and tissue engineering.

The Red Sea is largely undiscovered, strange wellspring of bioactive materials that its waters have not received sufficient and broad inspection till date. It expands for approximately 2000 kms and its semi segregation jointly with a rising saltiness at high water temperatures have offered new research trends for biological communities and developmental adjustments. Just a couple of marine green growths have been accounted for from the Red Sea up until now (27 passages in Algae Base rather than 512 for the Caribbean and 307 for the Arabian Gulf) and researches exploring the bioactivity of Red Sea algae are not many. Marine living beings have ended up being a rich wellspring of unprecedented and hopeful bioactive atoms for an extensive variety of uses, including novel therapeutics, cosmetics, and biotechnological applications. Marine algae, beside whichever benthic organisms, are predominately influenced by marine biofouling (epibiosis). It was confirmed that the aforementioned creatures yield secondary metabolites with antialgal, antibacterial, antifungal, anti-macrofouling and antiprotozoal characteristics in order to retain their surfaces without epibionts. Accordingly, natural yields from marine algae prove to be a favourable alternate source of unprecedented ecologically friendly compounds. Interestingly, exposing algae to light and high oxygen concentrations will stimulate the formation of inflammatory mediators like ROS and NOS. Consequently, algae are capable to produce the substantial compounds in order to protect themselves from external factors like UV radiation, stress and pollution. Generally, natural products are the main origin of compounds utilized in cancer therapy with over 75% of antineoplastic drugs in clinical research trials being either acquired or at least created by nature. Hence, marine algae possess a particular function since they are to an increasing extent significant dietary constituent in considerable portions of the world and are discussed as prospective, pharmaceutical foods in cancer management. In addition to the anti-cancer activity, marine algae display a multitude of anti-viral activities with an essential number of investigations concentrating on the human immunodeficiency virus type 1 (HIV-1), thereby exploring the significance of the aforementioned viral pathogen. HIV-1 keeps being a considerable human being health concern since there are more than 35.3 million people infected globally and 2.3 million new infections annually. Algal compounds were found to attack different steps of HIV-1 replication, covering viral entry and the main viral enzymes such as Reverse Transcriptase (RT), Integrase, and Protease. Furthermore, epidemiological discoveries indicate a consumption connection of marine algae with a low prevalence of HIV/AIDS in several Eastern Asia locations.

Chitin nanomaterials and nanocomposites are being used more frequently in tissue repair and skin rejuvenation. In fact, with the increase in age, the prevention of skin diseases became a necessity for our society together with an amelioration of the general body appearance. Thus, while medications have been revolutionized in their structure by the use of biodegradable and nature-oriented non-woven tissues, the use of natural polysaccharides polymers in cosmetics such as beauty masks are becoming increasingly manufactured and sold to the public. This chapter reports the biological properties and applications of biopolymers as well as discussing the physicochemical characteristics and the skin repairing activity of non-woven tissues based on the use of chitin nanofibrils obtained from biomass.