Perspective Chapter: Biomimetics – Bio-Inspired Tissular Engineering for Regenerative Oral, Dental and Cranio-Maxillo-Facial Solutions

Abstract

This chapter introduces the scope of the book—bioMIMETICS can be described as an innovative form of technology that imitates (or mimics) nature in order to improve human lives via creating desirable solutions. It is the study of nature and natural phenomena, principles, and underlying mechanisms, to obtain bio-inspired that may benefit various applied scientific and technological disciplines. Smart/Intelligent nano-bioMaterials for Tissue Engineering and Regenerative Medicine are a fine example. Yet, biomimicry can go above and beyond the simplistic inspiration and use of natural properties as the basis for innovation of new products. It bridges the gap between the lab and the industry, via the intra-disciplinary design and formulation of functional solutions combining knowledge, methods, techniques, and advances in the fields of chemistry, biology, architecture, engineering, medicine, pharmaceutics, dentistry, and biomedical engineering. Three-Dimensional Printing, Hybrid nanoCoatings, and Stimuli-sensitive and -responsive Cell/Drug Delivery Systems, and Robotics are some of the topics covered in this new book. In this first chapter, a general overview of bio-inspired materials, technologies, and strategies, collectively known as “bioMiMETICS,” is presented to bridge the gap between the laboratory “bench-top” and translational application, particularly, the clinic or “bed-/chair-side,” with a focus on “REGENERATIVE DENTISTRY” and the “CRANIO-MAXILLO-FACIAL bio-COMPLEX.”

1. Introduction

The Greek words “bios” and “mimesis”, for (life) and (to imitate), respectively, from the term “biomimetics,” hence, biomimicry, coined by Otto Schmitt, in 1957, can be now described as an innovative form of creative thinking, design, and technology that uses or imitates (or mimics) nature to improve human lives via creating desirable solutions and devices [1, 2, 3]. The paradigm idea of seeking inspiration from nature, the center ground or concept for biomimetics, is and cannot be thought of as recent field of study, discovery, and impact. It can be stated, that in R&D&I (research, development, and innovation), the biomimicry or bio-inspired approach (mind-set or point-of-view) has thus far contributed to how investigation is conducted by pointing (directing or guiding) the way toward a more sustainable practice and future. It is noteworthy perhaps herein that biomimetics is not sufficient by itself to translate its inspiration and lessons from nature to operational devices, solutions, or technologies. Hence, does not replace disciplines and specialties such as medicine and dentistry. Rather, biomimetics and biomedical engineering, for instance, need to interplay, alongside chemistry, biology, and physics, among other scientific fields, to lead to real applications that impact and benefit humankind and our patients (Figure 1). A symbiotic relationship similar to the coexistence and harmony of/between humans and nature. If, and when realized, biomimetics and its novel products can manipulate the WORLD [1, 2, 3, 4, 5, 6, 7]. bioMIMICRY is an art form based on science, accord, and purpose.

Figure 1.

Inter-/Intra-/Multi-Disciplinary interplay for bioMIMETIC Health Care.

Indeed, biomimetics perhaps corresponds to the consideration and comprehension (and inspiration by) of surrounding natural structures and functions, herein, of cellular and biological systems, alongside the conforming translation of the observed operative or operational principles as fundamental models for the creative design and development of novel technical systems with further enhanced properties [8]. Natural structural features have played a role in the evolution and enhancement of specific intrinsic material properties, later, providing ground for numerous technical applications and tools in architectural design and construction, advanced biomaterials, medicine and robotics, surface engineering and bio-coatings of medical and dental implants, to list a few examples [8, 9, 10]. Such, when supplemented with the accruing study of cellular (+ mesenchymal stem/stromal cell) behavior, interactions and communications alongside cell signaling and creating a controlled or adequate cell environment, tissue engineering, and regenerative medicine advances [1, 2, 9, 10, 11, 12].

In this first introductory chapter to the book, a general overview of bio-inspired and biomimetic materials, technologies, methods, and strategies is presented to bridge the gap between the laboratory “bench-top” and translational application, particularly, the clinic or “bed-/chair-side,” with a focus on DENTISTRY, in general, and the sub-specialty areas of Oro-Dental, Cranial, and Maxillo-Facial bio-Engineering.

Hwang et al. in 2015 [8] mentioned that biomimetics has a long history extending from knives and axes inspired by the dental structures of currently extinct animals to today’s strongest cutting-edge Carbon nanoMaterials employed in bioEngineering, passing through Leonardo da Vinci’s “flying machine” inspired by a bird and the Wright brothers’ powered airplane and the first successful human flight, back in 1903 [4, 5]. Hence, it has been noted, suggested, and/or suspected that biomimicry might actually date back to more than 2500 years ago, when artificial teeth were carved from the bones of oxen (ox or bullock), as the first attempt to replace body parts [8]. INSPIRING! Indeed, the substitution of natural materials by artificial biomaterials that mimic natural (original) tissue and tissular structure and function is yet another biomimetic approach; in fact, it is more prominent in tissue engineering and regenerative medicine. The idea of dental Dentin/Pulp renewal is a fine example (Figure 2) [13].

Figure 2.

bioMIMETICs date back to > 2500 years ago with carved OX-bone teeth.

2. Fibonacci’s sequence, ratio, and THE GOLDEN SPIRAL in bioMIMICRY

In 1997, the book “Biomimicry” by Janine M Benyus was published [14], suggesting (and even emphasizing) that biomimicry, via absorbing lessons from nature (as the groundwork for products rather than just a source for raw materials), is leading the path toward a new era of technological development. Indeed, biomimetic technologies arise from an inter-/intra-disciplinary flow of ideas, benefiting from the millions of years of creative design effort achieved by natural selection in living systems. Benyus, in 2002 (eBook in 2009) published a new book on how innovations inspired by nature are rapidly transforming the life on earth (Figure 3) [15].

Figure 3.

bioMIMICRY SPIRAL: IDEA to MARKET, following the “Golden Ratio.”

Hence, for a practical, convenient, operational, and/or translational (and profitable) bio-inspired design or innovation (reaching the end-user: consumer or patient for example), the biologically inspiring natural system or organism is to be studied and understood, rather than simply copying, fusing, or mimicking the creative design by itself [8, 14, 15]. In a study on how rabbits reproduce, a thirteenth-century Italian mathematician Leonardo Bonacci (later known as Leonardo Fibonacci) was the first to write (Liber Abaci, published in 1202) about the sequence found in nature and in the world around us, later referred to as the Fibonacci Sequence [16, 17, 18]. Basically, the sequence begins with 0 and 1, then continues with the sum of the two preceding numbers: 0, 1, 1, 2, 3, 5, 8, 13, 21, 34, 55, 89, 144, 233, 377, 610, 987, 1597, 2584, 4181, and so on (the sequence follows the golden rule that each number is equal to the sum of the preceding two numbers; i.e., each number is approximately 1.618 times greater than the preceding number), leading to calculating/applying (hidden inside the sequence) the golden ratio (phi = φ) and employing the golden spiral (a logarithmic spiral with a shape that is infinitely repeated when magnified, via A using quarter-circle arcs inscribed in squares generated from the Fibonacci sequence) in ordering and quantifications (and DATA-bases) [14]. To simplify further, φ is defined as the ratio of a rectangle with dimensions A x B where the ratio A/B is equal to (A + B)/A; regarded by many artists as the perfect proportion for a canvas. Fibonacci explained that these numbers are at the heart of how things grow in the natural world (Figure 4).

Figure 4.

Distinctives of bioMIMETICs and utility in Tissue/Organ bioEngineering.

Nature uses what it has grown so far to make the next move. It also helps describe predictable patterns on everything, from atoms and sub-atomics to huge stars in the sky [8, 14, 15, 16]. Interestingly, the ratio of the total number of chapters in the Quran (114), which represents the physical design of the Quran divided by the Quran Constant (70.44911244), which represents the mathematical design of the Qur’an (Koran) gives 1.6181893; it is amazingly equal to the golden ratio φ [19]. Nature uses this ratio to maintain balance, and the financial markets, for example, seem to do so as well. Fibonacci earlier explained how these numbers keep track of the population growth of rabbits. If a pair of rabbits take a month to mature before it can give birth to a new pair of rabbits, how many pairs of rabbits will there be each month? The answer is in the Fibonacci sequence [8, 14, 15, 16, 20]. Biomimicry is all about deep patterns and emulating the genius of genius to create conditions conducive to our Life; a more sustainable future. Velcro®, concentrated solar arrays and bioWAVE tidal energy are fine examples of implementing the Fibonacci Sequence, Ratio, and Spiral used to mimic the structural form and design functions of selected natural organisms for Innovative Design and re-Design [20]. Remember that nature-inspired design goes beyond structural, functional, or aesthetic similarities, and delves into the physico-chemico-mechanical and biological features of natural systems. Herein, for bio- or nature-inspired chemical, biological, medical, dental, and/or bioengineering, differentiating between (i) nature-inspired (or bio-inspired), (ii) nature-mimicking (or bio-morphism), or (iii) nature-integrated (or bio-integration) design, is perhaps critical. Perera and Coppens [21] recently examined those distinctive approaches, through illustrative examples, employed to deduce or outline a systematic methodology useful for translating innovative solutions, from the laboratory (bench-top) to market (bed-/-chair side/end-user); concept of “nature-inspired chemical engineering” [21]. Figure 5 demonstrates a micro-needle/medical adhesive patch device inspired by an electron micrograph of a spiny-headed worm (Pomphorhynchus laevis) that lives in fish by swelling the tip of its proboscis to anchor/latches itself to the flesh once inside the gut [22].

Figure 5.

Jeffrey Karp’s bio-medical adhesive patch developed at Harvard Medical School and Brigham and Women’s Hospital, where he is a bio-Engineer and Professor.

The creative adhesive device consists of a sheet of micro-needles whose tips swell upon contact with water, with potential applications in localized and targeted drug delivery and skin grafting (including burn wounds) among other possibilities. Combining polystyrene and polyacrylic acid, the adhesive micro-needles would replace traditional staples or sutures during plastic and reconstructive surgeries via providing multiple points of contact and adherence (universal soft tissue adhesion with minimal damage), thereby shortening the operative/surgical time [22]. Further, the patch can deliver antimicrobial or anti-inflammatory drugs directly to the skin graft sites while holding them together, in situ, thereby reducing the risk of infection and accelerating healing time for patients.

3. bioMIMETIC/bio-INSPIRED devices, fibers, robotics, and art designs

For this introductory chapter, other illustrative examples were compiled in an attempt to provide the reader with a different view on recent biomimetic innovations.

At Delft University of Technology (TU Delft) located in the Netherlands, researchers searched bio-inspiration to apply in designing novel surgical instruments and to improve how surgical techniques and procedures are performed [23]. A main driver was on finding a way to make rigid tools more naturally flexible steerable, yet without damaging nearby tissues (minimally-invasive), for use in knee arthroscopies, for example. Herein, creative mechanical engineering, inspired by snakes (Figure 6A) and their elasticity, helped develop such an arthroscopy tool that has a snake-like tip capable of bending, tentacle-like, yet in direct response to the hand movements of the operator/surgeon; a potential invention for robotic applications [23]. Figure 6B displays a stealth (infrared or IR) porous fibrous fabric (textile woven composed of aligned biomimetic fibers) inspired by the Polar bears and mimics the structure of their hairs [24]. Briefly, The Zhejiang University (ZJU China) researchers found that Polar hairs have a sponge-like hollow network core, which reflects back IR emissions from the animal body and helps prevent heat loss and thereby keeps the bears warm in their Arctic environments. Therefore, using fibroin (a protein in silk) and chitosan (from chitin) solution alongside a novel freeze-spinning method (developed for scale-up or large-scale production), they were able to continuously fabricate aligned, porous (87% porosity) micro-structured fibers (~200 μm wide) that are strong/sturdy, yet wearable and breathable, and highly thermally insulating, with capacity for active electro-heating if/when doped with Carbon nano-tubes, and application extending for commercial/personal insulation to military light-weight thermal management [24].

Figure 6.

Illustrating bioMIMICRY in different fields of innovation and socioeconomic impact. A. Surgical Tool inspired by Snakes and their flexible bio-mechanical movement, by TU Delft. B. Stealth and Heat-insulating Textiles inspired by the hairs of Polar Bears. C. Robotic Climbing System for Power Distribution Lines inspired by the Inch-Worm and how it moves and latches to surfaces. D. Architectural construction inspired by the shape and lattice structure of the Euplectella aspergillum.

In 2022, a novel modular biomimetic live working robot was designed and developed [25], inspired by the motion of inch-worms (which have two rows of legs on head and tail to latch, stick, or suck onto objects for bodily support), for use in the power distribution line, is depicted in Figure 6C. Basically, the 3-D rendered robotic system is intended to climb up the pole and complete the live working on power distribution lines, instead of the human operator, as a safer and more effective way to improve the reliability of power supply, especially in difficult or challenging areas such as mountains, as an alternative to traditional aerial lifts. The single-body robotic system (weighing less than 25 kg) demonstrated flexibility and rapidity in pole climbing via its modular design, thereby facilitating different configuration combinations in order to achieve different movement and performance requirements [25].

Finally, although unrelated to medicine or dentistry, Figure 6D displays a beautiful example, one of countless around the World, of biomimicry in Architecture and construction; Norman Foster’s iconic Skyscraper (of sustainable, high-tech and post-modern/neo-futurism architecture), also referred to as The Gherkin, in London's primary financial district. The building, completed in December of 2003 and opened in April of 2004, mimics the shape and lattice structure of the Venus Flower Basket Sponge (Euplectella aspergillum); a marine glass sponge in the phylum Porifera found in the deep waters of the Pacific Ocean (at depths ≤ 500 m). If interested in architectural design, check also the Institute du Monde Arabe in Paris, France, which mimics in its structure and façade the iris of the human eye. Irresistible to include architectural art and creative biomimetic design herein, to further emphasize that the idea of mimicking nature in man-made inventions is not new, and biomimetics is not solely (or limited to) the chemical, biological and/or medical. Furthermore, it is perhaps worth mentioning herein that the previously discussed golden ratio or Φ is also considered as one of the oldest rules in architecture, for example, in how transfer the weight of a massive building to its foundation. Indeed, the Fibonacci sequence has been used for centuries by man-kind for centuries, where architects leveraged Φ to create balance between the structural elements, as in the Pyramids of Giza in Egypt to the Parthenon Temple of goddess Athena on the Athenian Acropolis in Greece to the enormous Baalbeck Temple of the Phoenician sky god, Baal, in the Beqaa Valley of Lebanon. In essence, biomimicry can also be described as the learning and adapting processes from the wisdom of nature and its designs to then apply creatively and practically the inspired and acquired knowledge and sense to provide innovative and necessary solutions to help the humans and improve our World. In fact, biomimicry and biomimetics in health care can also be referred to or looked at as architectural medicine [26], emulating the time-tested patterns and strategies of nature to create new products, processes (and policies)—new ways of sustainable living—to challenging problems well-adapted to life on Earth, long-term.

4. bioMIMETICs advancing nano-bioMaterials, nanoTECHNOLOGY, and TISSUE ENGNEERING for bio-MEDICINE/-DENTISTRY and HEALTH

TISSUE ENGINEERING [27, 28], an inter-/multi-disciplinary approach, essentially, seeks to create tissues with optimal performance for clinical applications. Various factors, including cells, biomaterials, cell or tissue culture conditions (cell-cell and cell-material interactions), and signaling cues or molecules such as cytokines and growth factors, play a vital role in the engineering of musculo-skeletal tissues. Herein, the in vivo micro-environment of cells imposes complex and specific stimuli on the cells and has a direct effect on cellular behavior, including proliferation, differentiation, and extracellular matrix (ECM) assembly, as indicated earlier. Therefore, to create appropriate musculoskeletal tissues, the conditions of the natural environment around the cells should be well replicated, imitated, or mimicked [27, 28, 29, 30, 31, 32, 33, 34, 35]. Therefore, for engineering and creation closer to natural tissues in terms of appearance and function, researchers continue to attempt at developing biomimetic multifunctional scaffolds that can function better mechanically while producing the appropriate cellular responses in terms of cell signaling and cell adhesion. Indeed, in biomedical design, engineering principles are applied to medicine, dentistry, pharmacy, and cellular/biological systems for the objective of designing and translating novel pharmaceutical, tissue engineering, and regenerative medicine applications, methods, techniques, formulations, and tools for health care [28, 30, 31, 32, 33]. This includes therapeutics as well as analysis and diagnostics; thereby innovating solutions to challenging health problems. Fundamentally, bioMIMICRY, through various methodologies as well as new ideas on the creation of novel materials and functions, is how to mimic nature, as described previously. Nature has given us plenty of ideas on how to build composites and organized structure. In material and biomaterial science, the development of interfaces that integrate the functions of living cells and materials is key. Hence, the structure of a biomaterial influences cellular response(s) thereby determining the potential biomedical application(s). Modern nano-biomaterials, for example, are combinations of the unique properties offered by the organic and inorganic constituents of/from/within a single material, on a nano-scale; nanocomposites [8, 10, 21, 28, 29].

NANOTECHNOLOGY [21, 28, 31, 32, 33, 34, 35, 36, 37], emerged from the physical, chemical, biological, mechanical, and engineering sciences where novel formulation and characterization techniques and methods are developed to probe, manipulate, control and monitor single atoms and molecules (and combinations thereof). A nanoparticle (10⁻⁹ m) can be simply defined as a small, minute or tiny object that behaves as a whole unit in terms of its properties, characteristics, transport, and functions. Herein, it is perhaps worth mentioning that, today, the art, science, and engineering of nano-Systems are one of the most challenging and fastest-growing areas of nanotechnology, in general, and nano-biotechnology, in particular [28, 31, 32]. Why nano-scale and nanoparticles per se? Well, to simplify, as the size of the system decreases (from macro to micro to nano), a number of physical (amongst others) phenomena becomes more prominent and come into play. To rephrase further, an increase in the surface area to volume ratio leads to an enhancement of the behavior of atoms (more so on the surface of the nanoparticle rather than within/inside, herein), thus, altering the physical, chemical, mechanical, biological, optical, thermal, and catalytic properties of the whole material, or nano-System [28, 31, 32]. SPR (Surface Plasmon Resonance) and para-magnetism in metal-based magnetic nanoparticles, is a fine example. Anti-microbial property of Copper- or Silver-based nanoparticles [28, 38] is another, with increasing interest for utility in surgery and dentistry, given the superior inhibitory effect (sensitive as well resistant isolates of bacteria) against several microorganisms, including Streptococcus mutans, one of the main causative bacteria for Dental Caries or Decay. An illustration of biomimetics in dentistry versus traditional dentistry and its contribution to ultra-conservatism in the therapeutic strategies is shown in Figure 7.

Figure 7.

Traditional versus bioMIMETIC and Ultra-Conservative Dentistry of today, with applications in dento-alveolar tissue restoration, replacement, and repair.

5. bioMIMETIC cranio-facial tissue engineering and nanoDENTISTRY

The mechanical behavior of the cranio-maxillo-facial skeleton under physiological loads is among the least understood in the field of musculoskeletal bio-mechanics [38, 39, 40]. The musculoskeletal system contains a variety of supporting tissues, including muscle, bone, ligament, cartilage, tendon, and meniscus, which support the shape and structure of the body. Whether due to trauma, injuries, cancer, and/or diseases, defected, damaged, or lost tissue needs repair or replacement with healthy tissue [38, 39, 40, 41, 42]. Depending on the type of damaged tissue (whether it be cartilage, bone, skeletal muscle, tendon, and/or ligament), an extensive range of natural and synthetic (and composites thereof) biomaterials are available and possible, alongside simple and/or complex fabrication and formulation techniques, allowing to create a particular scaffold (porous scaffolds, 3D printed scaffolds, in situ-forming gels, bio-ceramics, and/or bioactive glass, electro-spun nano-Fibers, hydroxyapatite/collagen, and/or injectable hydrogels, amongst others); with an essential role in the regeneration, restoration, reconstruction, and repair (or replacement) of the musculoskeletal system, bearing in mind its governing structural bio-mechanics [32, 33]. In regenerative medicine, several factors should be taken into account when designing a system for successful organ regeneration using tissue engineering principles, including: (i) resident or transplanted cells should differentiate into specific cell types within a biomimetic matrix; (ii) the biomimetic matrix should provide biological and mechanical support for cell growth and function; (iii) the biomimetic matrix should allow for growth factor/cytokine permeation and physiological signals/cues; and (iv) the biomimetic matrix should have high engraftment efficiency [28, 30, 31, 32, 38]. Hence, designing, developing, characterizing, evaluating, and/or testing (then fine-tuning or optimizing) systems that encompass all of the above ideal characteristics have proved challenging. For example, the most commonly used in vitro culture techniques, today, do not mimic all of the micro- and nano- environmental factors that direct cell differentiation into a developing organ.

NANOTECHNOLGY in medicine (reputed as nanoMedicine) or/and in dentistry (reputed as nanoDentistry) has opened new realms and provided novel solutions for such demanding characteristics, properties, and needs (to full the criteria for proper tissue engineering and regenerative medicine/dentistry) [43, 44]. Specifically, it has done so by developing desirable and superior materials to control the physical/structural, chemical, biological, and mechanical micro-environment, critical for, successful cell (gene- and drug-) delivery and tissue regeneration [28, 32, 33, 34, 35, 36, 37]. Therefore, manipulating biomaterials to create material surfaces and structures with nano-scale features (nano-bioMaterials) not only can help mimic the native micro- and nano-environment of cells, but also can trigger (and direct or guide – control and modulate) select cell adhesion, growth, proliferation, and differentiation with/without the use of drugs [28, 45, 46, 47, 48]. Figure 8 depicts the role of natural polymers (polysaccharides) from different eco-sources in designing, formulating, and developing nano-bioMaterials for Tissue bioEngineering and Regenerative Medicine.

Figure 8.

Natural Polymer-based nanomedicine and nanoDENTISTRY. Natural Polysaccharides are abundant, biocompatible, biodegradable and have been incorporated, whether alone or in combination (in addition to other cells, genes, drugs, molecules, etc.) in carriers, matrices, scaffolds, and delivery systems for cell therapy, pharmaceutics, oncology, tissue engineering, and regenerative applications.

The generation of new organic/inorganic analogs [45, 46, 47, 48] of Carbon-based nano-bioMaterials (including graphene) for stem-cell-based tissue engineering, using nano-fibrous scaffolds and hybrid hydrogels as carriers or matrices, is a fine example. Further, since bone is a nano-composite, by nature, containing nano-scale building blocks (mainly collagen fibrils and mineral hydroxyapatite plates), the use of biodegradable conductive nano-composites is attractive for orthopedic, cranio-maxillo-facial and oro-dental applications [31, 35, 36, 37, 39, 40, 41, 44, 49, 50]. Therefore, many examples are found in literature where nano-bioMaterials allow for better hard, bone (and soft) tissue regeneration, providing a better surface and physicochemical properties for osteoblast attachment and long-term function. Better mechanical properties for certain load-bearing conditions in orthopaedic applications [31, 36, 39, 40, 41, 44, 49, 50] as well as in oral and maxillofacial implantology (i.e., dental Titanium or Ti implants and Ti implant-retained dentures, also known as overdentures—for the edentate or completely edentulous patient) [51, 52] have been also feasible, herein.

To recap, scaffolds developed for tissue engineering and tissular regeneration, trying to mimic the natural extracellular matrix, require a good control of porosity, inter-connectivity between pores, and even the size of pores. The macro-, micro-, and nano-architecture of 3D scaffolds (for soft and hard tissue engineering, repair and regeneration) have a primordial relevance to replicate the structural complexity of living tissues. Today, hybrid systems considering multiple material mixtures and a combination of fabrication processes are fundamental to mimic the natural tissues by providing multi-phasic or multi-material structures, accommodate growth factors and cells, and supply the signaling cues, vital to guide cell adhesion and proliferation [31, 35, 36, 37, 39, 40, 41, 44, 49, 50]. Remember, depending on the nature of the target defective/damaged/lost tissue and the required mechanical, chemical, and biological properties, different biomaterials can be employed, either singly or in combination, or with other additive materials [31, 35, 36, 37, 39, 40, 41, 44, 49, 50]. Further, although bone, described above as a natural nano-composite, a connective tissue with the ability to heal/regenerate spontaneously, in several specific cases, such as critical-sized defects, it fails to do so. It is important to consider the mechanical conditions affecting bony regeneration and the influence of the surrounding environment [49, 53, 54]. The quality of the soft tissue covering the defect is detrimental, also [50, 54].

In craniofacial defects, for example, reconstructive surgeons collaborate with engineers to design and create, fabricate, or formulate complex 3D geometrically structured or printed scaffolds, for a more personalized (patient-specific) corrective approach, regardless of the size or anatomic location of the cranio-maxillo-facial defect [38, 50, 54]. The potential benefits of using a tissue engineering approach include reduced donor site morbidity, shortened operative time, decreased technical difficulty of the repair, and, most important, ability to closely mimic the in vivo micro-environment, to attempt recapitulating normal cranio-maxillo-facial development [38, 50, 54, 55, 56, 57, 58, 59]. Whether resulting from trauma, pathology, and/or osteonecrosis, mechanically stable and space-maintaining scaffolds tailored to site-specific defects, should be osteogenic, osteoconductive, osteoinductive while promoting angiogenesis and vasculogenesis [56, 59, 60]. Herein, it is critical to achieve a balance between the engineering the physiological criteria, for more safe and efficacious devices, to prevent and overcome infection, wound dehiscence, pre-mature resorption, and/or graft/implant failure. As one of the three essential components of tissular regenerative engineering, biomimetic NANOTECHNOLOGY is shifting the paradigm of employable nano-bioMaterials and holds promise for the future generation of substitute tissue grafts, including 3D printed and hybrid scaffolds [60].

REGENERATIVE DENTISTRY [61, 62] approaches include the formation of new enamel, dentin, pulp, periodontal ligament, and alveolar bone after tooth damage due to genetic pathology, traumatic injuries, caries, and periodontal lesions. Recent progress in the fields of mesenchymal stem/stromal cell biology (including, oral- and dental-derived), tissue engineering, and nanotechnology is considerable and offers new concepts and promising opportunities to repair, restore, and/or replace damaged or missing oral and dental tissues; modern dental treatment strategies and protocols. Likewise, scaffolds are key elements for the success of oro-dental tissue regeneration [12, 39, 61, 62, 63]. Indeed, in regenerative dentistry (dento-alveolar structures and tissues), emerging technologies such as bio-printing continue to be developed to solve some of the shortcomings of traditional tissue engineering approaches [56, 61]. For example, automated bio-printing facilitates the creation of geometrical patient-specific scaffold designs and in parallel permits the precise placement of cells and biological molecules thereby producing a biological or bioactive personalized scaffold [56, 61, 64, 65]. Yet, translation into a clinical product and our patients is still challenging, as the choice of a suitable material to encapsulate cells (and the other essential biological factors) in the development of the “bio-inks,” for instance, for ultimately or pertinently bio-printing the heterogeneous dento-alveolar tissues (such as the pulp-dentin complex and the periodontal ligament, surrounding the tooth and filling the space between the tooth and its socket in the alveolar bone), is intricate and still posing technical hurdles and economic constraints [61, 64, 65, 66, 67]. Yet, it is perhaps worth mentioning that R&D&I [60, 61, 62, 63, 64, 65, 66, 67, 68, 69] on bio-printing dento-alveolar tissue, in particular, is still in the early stages, however, alongside accruing advancements in nano-science (novel sophisticated composites and fillers), tissue engineering techniques, biomimetic scaffolds (that also provide geometric cues for de novo tissue regeneration), stem/stromal cell-based therapeutics, autologous cell grafting, platelet concentrates (including platelet-rich fibrin), inkjet-based 3D printing (fabricated calcium phosphate or CaP scaffolds, for example), additive manufacturing (by extrusion: deformation + solidification, laser-assisted sintering or polymerization, for example), and rapid prototyping (for visual and informative models) , laser-scanning, computer-aided design and computer-aided manufacturing (that can manipulate 3D computed tomography images of bone, for example, virtually and in real-time) as well as in the available imaging and diagnostic techniques (that can verify and quantify the degree of mineralization and vascularization of the implanted scaffolds at the earliest stages of tissue regeneration), to list a few, the future, undoubtedly, brings new horizons and ample hope for innovative (and a new era of) oro-dental and cranio-maxillo-facial treatments, to all our patients and clinics.

6. Conclusions

BioMIMETICs is a research, development, and innovation field that is attaining growing interest and accruing prominence through an unprecedented flood of new discoveries and technologies in biology and creative engineering. From less than a hundred articles per year in the 1990s to several thousand studies and publications, annually, in the last decade, with impact “theoretical” across disciplines and diverse biomedical and bioengineering themes, including artificial intelligence, robotics, bioinformatics and omics. Biomimetics, today, is the leading scientifically-relevant paradigm for the innovative potential design and guiding the advancement of new methods and devices, for a high scientific, medical, and socio-economic impact, soon.

REGENERATIVE DENTISTRY employs the accruing understanding of cellular and molecular biology into the creative (and patient-specific) design of oral, dental, and cranio-maxillo-facial therapies that ultimately aim to restore, repair, rejuvenate, replace, and/or regenerate defected, damaged/injured or lost tissues. For the future of clinical and surgical dentistry, the grand challenge for bioMIMICRY incorporating and influencing (or inspiring) tissue engineering and regenerative nano-bioMaterials is to boost funding, expedite high-quality research, clinical translation, and education.

DRUG DELIVERY, in particular release-controlled and -targeted systems, of therapeutic agents (including cells, proteins, genes, anti-microbials, and so on), using bio-polymeric materials (such as, injectable and/or stimuli-responsive hydrogels and nano-Fibers whether electro-spun, 3D printed or produced through a combinatorial/Hybrid approach/methodology) and colloidal vesicles (such as, liposomes, solid lipid nanoparticles, core-shell nanocapsules, and micelles), have been introduced, yet, critical challenges still remain, as most of technologies are subpar and fail to reach clinical expectations. Novel pharmaco-kinetic approaches, inspired by nature, could perhaps provide alternative, superior, and safer dose-responsive, and targeted solutions, for more precise and sustainable pharmaceutics.

Bio-TOOTH [70], the bio-Engineered and fully functional tooth explant from adult (embryonic-like) cells, as a replacement for the Ti-metal dental implant, although not yet realized, it is becoming more realistic, with the recent advances discussed in this chapter. Perhaps, to better understand on how to realize the bio-tooth, someday, it is good to seek inspiration and clues from nature and the evolution studies on species, such as fish and reptiles, which continuously replace their teeth? BioMIMICRY may help.

Acknowledgments

This work was supported by operating grants provided to the BioMAT’X I+D+I Group (HAiDAR R&D&I LAB: Laboratorio de Biomateriales, Farmacéuticos y Bioingeniería de Tejidos Cráneo Máxilo-Facial), a member of the Centro de Investigación e Innovación Biomédica (CiiB), Faculty of Medicine, Universidad de los Andes, through the awarded project funds: (1) NAM-USA / ANID-Chile # NAM 21I0022 “SockGEL/PLUG” (2021–2023), (2) CORFO Crea y Valida # 21CVC2-183649 (2022–2024) “bioFLOSS”, (3) CORFO Crea y Valida—Proyecto de I+D+i Colaborativo—Reactívate # 22CVC2-218196 (2022–2024) “EndoCOAT’X,” and FONDEF IDEA DE I+D, SUBDIRECCIÓN DE INVESTIGACIÓN APLICADA/ANID 2022, # ID22I10215 (2023–2025) “maxSALIVA.”

Conflict of interest

The author declares no conflict of interest.

Notes/thanks/other declarations

I would like to thank Ms. Ana Javor and Mr. Josip Knapic, Author Service Manager(s) at IntechOpen for their constant support, communication, feedback and in the timely preparation of our project “Biomimetics – Bridging the Gap,” with content, to the best of abilities, different from what has been previously published. THANK YOU and hope for the next.