Introduction to Biomimicry

### **Chapter 1**

## Introductory Chapter: bioMimetics for HealthCare – Innovations Inspired by Nature

*Ziyad S. Haidar*

### **1. Introduction**

This chapter collectively aims to imitate the biological processes or systems in which nature solves problems or tackles tasks, using our world as a source of inspiration and as a guide in the design and development of new biomaterials and solutions—*innovations*.

Therefore, biomimicry is a fusion of approaches requiring the detection, perception, observance, identification, and detailed study of systems and organisms within nature, in order to use as bio-inspired models (basis) for novel scientific, technical, and technological solutions, suitable for interventional application in dentistry and medicine, including tissue bio-engineering. Such a journey also invites elucidating the underlying mechanisms and relationships between the structure and function of the stimulating natural system(s) for applied and/or translational biomimesis, biomimicry or biomimetics, to us humans, whether as sole individuals or in groups and when healthy end-users/-consumers or patients needing therapies [1].

#### *Biomimetics - Bridging the Gap*

Since Janine Benyus published her dominant book in 1997 [2], it can be stated that biomimicry has experienced the swift rise in the attention we have been witnessing. She outlined three essential or fundamental components for sustainable biomimicry *active study of natural systems as source (unlimited supply) of inspiration for new bio-solutions*: (1) nature as model; (2) nature as measure; and (3) nature as mentor. Biomimicry can thus be depicted as an art form based on science, accord, and purpose.

It can also be stated, today, that in R&D&I (research, development, and innovation), the biomimicry or bio-inspired approach (mindset or point-of-view) has thus far contributed to how an investigation is conducted by pointing (directing or guiding) the way towards 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 human-kind and our patients: *a symbiotic relationship similar to the co-existence and harmony of/between humans and nature*. If, and when realized, biomimesis and its products can manipulate the WORLD [3–5].

#### **2. Medical bioMimicry market: market size, present trends and forecasts**

According to the most recent 130-page study by Global Market Insights Inc. (August of 2021 [6]), a global market research and consultancy service headquartered in Selbyville Delaware-USA, the medical biomimetics market size is anticipated to record a valuation of USD\$ 53 billion by 2027, driven by the boost in adoption of new techniques by the industry players for the provision of advanced devices to end-users. This increase or expansion is despite the losses incurred by the COVID-19 pandemic. The report provides penetrative insights presented to aid in strategic decisionmaking, highlighting the major trends that are likely to transform the medical biomimetics market landscape in the coming years, mainly attributed to the increasing burden of numerous healthcare challenges requiring novel solutions. Amongst those, *Tissue Engineering and Regenerative Medicine* (as a segment) is anticipated to grow at a startling CAGR of 7.5% between the period 2021 and 2027. Furthermore, the medical biomimetics industry is anticipated to continue its growth worldwide, also due to longevity and the increasing senior or geriatric population, and the surging prevalence of neurological, cardiovascular, and orthopedic diseases.

Another is the *Drug Delivery* segment, exceeding USD\$ 6.5 billion in 2020, of the medical biomimetics market, mainly attributed to the increased demand and growing adoption of 3-dimensional biomimicry-based models and nano-Carriers (including nanotechnology-scaled/enabled vaccine release) in controlled drug delivery systems.

In *Dentistry*, particularly, biomimetic products that aid in (a) battling against oro-dental biofilm formation and (b) treating tooth/teeth disorders (conservative and ultra-conservative dentistry for the prevention and treatment/restoration of intact natural dentition) from decays/caries, gingival and periodontal diseases, pulp conditions and trauma/fractures, to list a few, is, also projected to considerably grow from the accounted > USD\$ 3.5 million (*segment*) of the medical biomimetics market, in 2020. Interestingly, the market study [6] reported on the significance and impact of the recent advancements in the field of nanotechnology, expanding in the healthcare sector, as the demonstrated dynamic biomimetic behavior rendered

*DOI: http://dx.doi.org/10.5772/intechopen.106328 Introductory Chapter: bioMimetics for HealthCare – Innovations Inspired by Nature*

feasible for exemplifying single cells at high output, concluding that such scientific, technical, and technological developments will open the door wider for nanobiomimetics (novel material composites and pharmaceutics) boosting the Medical Market, in the future.

Prominent major players and competitors operating in the medical biomimetics market include Abbott, BioHorizons, Biomimetics Laboratories Inc., BioTomo Pty. Ltd., Avinent Implant System, Hstar Technologies corporation, and Veryan medical among others. Herein, collaborations, partnerships, and acquisitions are among the various business strategies recently visibly adopted to enhance the co-market share [6]. Finally, the clinical and regulatory requirements for approving the translation of biomimetic products continue to present a stringent hurdle and challenge to them.

#### **3. Nature as R&D&I laboratory: examples of biomimetic HealthCare**

Nature retains an unlimited imagination. Japan's famous high-speed 240–320 km/h *Shinkansen bullet* train [7] was inspired by the shape of the Kingfisher's beak (*Alcedinidae*), a small to medium-sized brightly colored bird with long,

narrow-pointed, and dagger-like beak allowing to dive into the water without splashing to catch prey. Not only did this bio-inspiration help to reduce noise and eliminate tunnel booms, yet also allowed the train to travel 10% faster using 15% less electricity. A US-Canadian team (finalists for the European Inventor Award in 2018) innovated turbine blades with three-dimensional bumps [8] on their leading edges based on viewing the "bumpy" flippers (tubercles) of humpback whales (*Megaptera novaeangliae*). They discovered that this helped the 14–18 m long and ~40 metric ton fish reduce unwanted whirling masses of air (vortices), thereby reducing drag while simultaneously increasing lift. The team's improved turbine aerodynamic performance can help wind farms generate up to 20% more power and increase airflow by up to 25% in industrial fans and blowers, whilst producing less noise by at least 2 decibels and requiring less maintenance (life-time of wind turbine increased by 25%). Henceforth, and given such competitive benefits (~20% better) to market leaders, their first licensed product is forecasted to be worth ~USD 10 billion in 2022.

In HealthCare, studies in biomedical technology, bioengineering, and dental biomaterials, for example, have already shown that our science and engineering cannot currently *out-perform* many of nature's capabilities. The COVID-19 pandemic reminded us that we are constantly vulnerable to life-threatening invasions from bacterial species, many of which have existed on the planet billions of years before us. Biomimicry [9, 10], the study of the formation, structure, and function of biologically produced substances and materials, mechanisms, and processes, as stated earlier, can help design, develop, formulate, fabricate and translate new biosolutions.

For example, Biomatrica [11], a subsidiary of Exact Sciences Corporation (following acquisition in 2018 for USD\$ 20 million), a Wisconsin-based molecular diagnostics and cancer screening company, to overcome the problem that many vaccines are lost due to breaks in refrigeration during shipping and treatment (a hurdle we all witnessed during the Coronavirus infectious disease or COVID-19 caused by the SARS-CoV-2 virus pandemic), adapted and incorporated into their product a process (ambient temperature storage reagents for DNA and RNA) inspired from the Tardigrade, a millimeter-long cousin of the arthropods. Briefly, these creatures employ a protective process called *anhydrobiosis*, which safeguards their DNA, RNA, and proteins until water revives them, even though they can dry out for up to 120 years. Basically, the tardigrade releases trehalose, a simple sugar molecule and as the water leaves their cells, the trehalose replaces where the water once was, and the cell membrane releases the water and bonds to the sugar instead, hence, by doing this, the proteins stay in the same place that they would be when fully hydrated. The company used this bioinspiration to protect live vaccines so that they no longer need to be refrigerated. Such can be helpful for vaccinating vulnerable populations in tropical areas. SB 3000 [12] or Swedish Biomimetics 3000, a ground-breaking life science and pharmaceutical company headquartered in Copenhagen-Denmark, found inspiration in the defense mechanism of ground carnivorous *Bombardier* beetles (*Carabidae*) to develop a micro-mist spray technology with potential application in nebulizers (a type of breathing machine that lets you inhale medicated vapors), called μMIST, that has a lower carbon print/impact than aerosol sprays, as it does not require a propellant to work (spray highly-viscous formulations). Those beetles, when disturbed, repel attacking insects by ejecting a hot (near-boiling temperature) noxious chemical spray produced (via a chemical reaction between hydroquinone and hydrogen peroxide) in their abdomen (alongside a popping sound). At Kansai University in Osaka-Japan [13], a team of engineers found inspiration in mosquito bites, replicating their *proboscis*, to develop pain-free needles and injections, to replace the conventional

#### *DOI: http://dx.doi.org/10.5772/intechopen.106328 Introductory Chapter: bioMimetics for HealthCare – Innovations Inspired by Nature*

hypodermic steel needles, that despite being smooth, do penetrate deep and leave ample metal contact with skin tissue hence causing us pain. Studies revealed that mosquitos inject us by vibrating their proboscis to help the serrated sections of their maxillae ease down, with least sensation possible, through our skin. We do not feel the bite itself because this small-/close-contact mechanism reduces friction and in consequence, nerve stimulation, but feel discomfort *afterward* because the mosquitos inject bacteria that cause irritation and pain [13].

For bioprinting, a novel bio-ink incorporating Hyaluronic Acid (HA), a natural linear polysaccharide found in many tissues throughout the human body, was recently developed by Rutgers University in New Jersey and one of America's leading public research universities [14]. Herein, the HA bio-polymer, whose main function is to retain water to keep tissues well lubricated and moist, is also well known to play an important role in regulating cell differentiation, migration, angiogenesis, and inflammation/immunological responses. Briefly, the bio-ink material is made of modified HA and polyethylene glycol to serve as the basic "ink cartridge" for the 3-D printing of different scaffolds (in a range of physico-chemico-mechanical/rheological and biological properties; personalized/customized design and manufacturing) that can be employed for growing, restoring and replacing the lost and/or defective human tissues, overcoming few of the main challenges in the field of 3-D bio-printing.

Inspired by squid [15], a *mollusc cephalopod* with an elongated soft body, large eyes, eight arms, tentacles, and more particularly the teeth present in ring formations inside suction cups on those tentacles, researchers Penn State University in Pennsylvania-USA, developed a self-assembled composite material with tunable electric properties for bio-engineering use. Herein, they noticed that the squid ring teeth are made up of proteins that can combine (or assemble) in different ways to help the squid grip onto a surface or grasp prey. Also, if the teeth break, they can self-heal. The structure of the squid ring teeth proteins (tandem repeat proteins) helped inspire a solution to problems in creating mixtures (matrix-to-filler ratios, in tiny or small areas) with highly-tunable properties, suitable for improving electronic devices, such as diodes or regulators, as well as topologically-networked biomaterials to isotropically and anisotropically modulate the "electronic transport" in composites.

Biomimetic Dentistry (including regenerative dentistry) [16], on the other hand, is the art and science of clinically restoring damaged teeth and using materials that mimic the properties of natural teeth—in terms of strength, appearance, and function (main reference to adhesive materials in restorative dentistry). Indeed, according to the Academy of Biomimetic Dentistry [17], the biomimetic dentistry approach (and currently-available materials) can help dentists conserve as much of the tooth structure as possible, preserve tooth vitality and prevent unnecessary damage to root canals, restore teeth that would otherwise (traditionally) need an extraction, increase the bond strength of dental restorations by 400%, minimize shrinkage stress on the teeth, eliminate sensitivity/pain, and create long-lasting restorations that prevent complications often experienced with conventional approaches. 3-D printing might also be helpful for the next generation of bone grafts to clinically-create on-demand patient-specific scaffolds [18, 19]. Indeed, in the developing area of regenerative dentistry, the "bio-tooth" [20], perhaps is a fine biomimesis or biomimicry example, *in pursuit*. Herein, for a bio-engineered and fully-functional tooth, the *synergistic* employment of the accruing understanding of the underlying cellular and molecular biology into the creative (and patient-specific) design of oral, dental (and craniomaxillo-facial therapies) that ultimately aim to restore, repair, rejuvenate, replace and/or regenerate defected, damaged/injured or lost tissues is *key*. Collectively, alongside incorporating tissue engineering and regenerative nano-biomaterials would boost and expedite high-quality research to eventually realize it.

#### **4. Conclusions**

The examples illustrating biomimicry for health and in novel healthcare applications are plenty, and some will be explored within the chapters of this book, to further demonstrate the innovative form of biomimetic technology that imitates (or mimics) nature to improve human lives via creating desirable solutions. To re-emphasize, such a process requires the study of nature and natural phenomena, principles, and underlying mechanisms, to obtain bio-inspiration that may benefit various applied scientific and technological disciplines. Smart/Intelligent nano-biomaterials for Tissue Engineering, Regenerative Medicine and Regenerative Dentistry is a fine example. It is also perhaps worth mentioning in this *introductory chapter* that biomimicry can go above and beyond the *simplistic* bio-inspiration and use of natural properties as the basis for innovation and translation of new products to the demanding market of end-users and patients. It can bridge 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, and dentistry, alongside contributions from artificial intelligence, robotics, bio-informatics, and omics. Indeed, biomimesis, today, can be considered the leading scientifically-relevant paradigm for innovative design and the guide for advancing new methods and devices, for a higher scientific,

*Introductory Chapter: bioMimetics for HealthCare – Innovations Inspired by Nature DOI: http://dx.doi.org/10.5772/intechopen.106328*

technological, technical, medical, and socio-economic impact. There is still much to learn from nature and the world around us, including ourselves since we are one of the most successful end-products and -users.

#### **Acknowledgements**

This work was supported by operating grants provided to BioMAT'X I+D+I (HAIDAR LAB: Laboratorio de Biomateriales, Farmacéuticos y Bioingeniería de Tejidos Cráneo Máxilo-Facial), a member of CiiB, Faculty of Medicine, Universidad de los Andes, through the awarded project funds: (1) NAM-USA/ANID-Chile # NAM 21I0022 (2021-2023) and (2) CORFO Crea y Valida # 21CVC2-183649 (2022-2024).

#### **Conflict of interest**

The author declares no conflict of interest.

### **Notes/thanks/other declarations**

I would like to thank Mr. Josip Knapić, Author Service Manager at IntechOpen for his 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.

#### **Author details**

Ziyad S. Haidar Faculties of Medicine and Dentistry, BioMAT'X (HAIDAR LAB) R&D&I, Biomedical Research and Innovation Center (CiiB), University of the Andes, Santiago, Chile

\*Address all correspondence to: zhaidar@uandes.cl; zhaidar78@gmail.com

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

#### **References**

[1] Benyus JM. Biomimicry. HarperCollins e-Books; New York, USA. 2009

[2] Benyus JM. Biomimicry: Innovation Inspired by Nature. New York: William Morrow and Co; 1997. p. 308

[3] Ilieva L, Ursano I, Traista L, Hoffmann B, Dahy H. Biomimicry as a sustainable design methodology— Introducing the 'Biomimicry for Sustainability' framework. Biomimetics. 2022;**7**(2):37

[4] Perera AS, Coppens MO. Re-designing materials for biomedical applications: From biomimicry to nature-inspired chemical engineering. Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences. 2019;**377**(2138):20180268. DOI: 10.1098/ rsta.2018.0268

[5] Haidar ZS. Bio-inspired/-functional colloidal core-shell polymeric-based nanosystems: Technology promise in tissue engineering, bioimaging and nanomedicine. Polymers. 2010;**2**:323-352

[6] Report ID: GMI767 Published Date: Aug 2021-Medical Biomimetics Market Size By Product (Cardiovascular, Orthopedic {Prostheses, Exoskeleton}, Ophthalmology, Dental), By Application (Plastic Surgery, Wound Healing, Tissue Engineering, Drug Delivery), COVID-19 Impact Analysis, Regional Outlook, Application Potential, Competitive Market Share & Forecast, 2021-2027. Available from: https:// www.gminsights.com/toc/detail/ medical-biomimetics-market

[7] Shinkansen-The Japanese bullet trains. Available from: www.jrailpass. com/shinkansen-bullet-trains and asknature.org/innovation/

high-speed-train-inspired-by-thekingfisher/

[8] Patent # US20090074578A1Turbine and compressor employing tubercle leading edge rotor design. Inventor: Stephen W. Dewar, Phillip Watts and Frank Eliot Fish. Available from: https://worldwide.espacenet.com/ publicationDetails/biblio?DB=EPODO C&II=0&ND=3&adjacent=true&locale =en\_EP&FT=D&date=20070711&CC=E P&NR=1805412A1&KC=A1

[9] Upadhyay A, Pillai S, Khayambashi P, et al. Biomimetic aspects of oral and dentofacial regeneration. Biomimetics (Basel). 2020;**5**(4):51

[10] Hwang J, Jeong Y, Park JM, Lee KH, Hong JW, Choi J. Biomimetics: Forecasting the future of science, engineering, and medicine. International Journal of Nanomedicine. 2015;**10**:5701-5713

[11] Biomatrica. Exact Sciences Corporation, Wisconsin, USA: Available from: https://www.sbir.gov/sbc/ biomatrica-inc

[12] Swedish Biomimetics 3000, Copenhagen-Denmark. Available from: https://sb3000.tech/

[13] Tolfree D, Smith A. A painless bite. Physics Review. 2018;**27**(4):18-20

[14] Godesky MD, Shreiber DI. Hyaluronic acid-based hydrogels with independently tunable mechanical and bioactive signaling features. Biointerphases. 2020;**14**(6):061005. DOI: 10.1063/1.5126493

[15] Vural M, Zhu H, Pena-Francesch A, Jung H, Allen BD, Demirel MC.

*Introductory Chapter: bioMimetics for HealthCare – Innovations Inspired by Nature DOI: http://dx.doi.org/10.5772/intechopen.106328*

Self-assembly of topologically networked protein-Ti3C2Tx MXene composites. ACS Nano. 2020;**14**(6):6956-6967. DOI: 10.1021/acsnano.0c01431

[16] Sharpe P. Regenerative dentistry. Frontiers in Dental Medicine. 2020;**1**:3. DOI: 10.3389/fdmed.2020.00003

[17] Academy of Biomimetic Dentistry. Available from: https://www.aobmd.org/

[18] Ashammakhi N, Kaarela O. Threedimensional bioprinting can help bone. The Journal of Craniofacial Surgery. 2018;**29**:9

[19] Zhang L, Yang G, Johnson BN, Jia X. Three-dimensional (3D) printed scaffold and material selection for bone repair. Acta Biomaterialia. 2019;**84**:16-33. DOI: 10.1016/j.actbio.2018.11.039

[20] Mitsiadis TA, Harada H. Regenerated teeth: The future of tooth replacement. Regenerative Medicine. 2015;**10**:5-8. DOI: 10.2217/rme.14.78

#### **Chapter 2**

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

*Ziyad S. Haidar*

#### **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."

**Keywords:** biomimetics, dentistry, tissue engineering, regenerative medicine, surgery, bioprinting, scaffolds, hydrogels, nanotechnology, biomaterial innovation

#### **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 [1–3]. The paradigm idea of seeking inspiration from nature,

#### *Biomimetics - Bridging the Gap*

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 [1–7]. bioMIMICRY is an art form based on science, accord, and purpose.

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

**Figure 1.** *Inter-/Intra-/Multi-Disciplinary interplay for bioMIMETIC Health Care.*

#### *Perspective Chapter: Biomimetics – Bio-Inspired Tissular Engineering for Regenerative Oral... DOI: http://dx.doi.org/10.5772/intechopen.109113*

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 [8–10]. 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, 9–12].

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

**Figure 2.** *bioMIMETICs date back to > 2500 years ago with carved OX-bone teeth.*

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].

#### **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].

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

**Figure 3.** *bioMIMICRY SPIRAL: IDEA to MARKET, following the "Golden Ratio."*

*Perspective Chapter: Biomimetics – Bio-Inspired Tissular Engineering for Regenerative Oral... DOI: http://dx.doi.org/10.5772/intechopen.109113*

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 [16–18]. 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**).

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, 14–16]. 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

**Figure 4.** *Distinctives of bioMIMETICs and utility in Tissue/Organ bioEngineering.*

(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, 14–16, 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 physicochemico-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

#### **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.*

*Perspective Chapter: Biomimetics – Bio-Inspired Tissular Engineering for Regenerative Oral... DOI: http://dx.doi.org/10.5772/intechopen.109113*

(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].

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].

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

#### **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.*

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 *Perspective Chapter: Biomimetics – Bio-Inspired Tissular Engineering for Regenerative Oral... DOI: http://dx.doi.org/10.5772/intechopen.109113*

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 [27–35]. 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, 30–33]. 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

#### *Biomimetics - Bridging the Gap*

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, 31–37], 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

#### **Figure 7.**

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

*Perspective Chapter: Biomimetics – Bio-Inspired Tissular Engineering for Regenerative Oral... DOI: http://dx.doi.org/10.5772/intechopen.109113*

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. Antimicrobial 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**.

#### **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 [38–40]. 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 [38–42]. 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, 30–32, 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.

#### *Biomimetics - Bridging the Gap*

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, 32–37]. Therefore, manipulating biomaterials to create material surfaces and structures with nano-scale features (nano-bioMaterials) not only can help mimic the native microand 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, 45–48]. **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.

The generation of new organic/inorganic analogs [45–48] 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, craniomaxillo-facial and oro-dental applications [31, 35–37, 39–41, 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, 39–41, 44, 49, 50] as well as in oral and maxillofacial implantology (*i.e.*, dental Titanium or

#### **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.*

*Perspective Chapter: Biomimetics – Bio-Inspired Tissular Engineering for Regenerative Oral... DOI: http://dx.doi.org/10.5772/intechopen.109113*

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 multiphasic or multi-material structures, accommodate growth factors and cells, and supply the signaling cues, vital to guide cell adhesion and proliferation [31, 35–37, 39–41, 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, 35–37, 39–41, 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, 54–59]. 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, 61–63]. 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, 64–67]. Yet, it is perhaps worth mentioning that R&D&I [60–69] 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/

*Perspective Chapter: Biomimetics – Bio-Inspired Tissular Engineering for Regenerative Oral... DOI: http://dx.doi.org/10.5772/intechopen.109113*

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 biotooth, 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.

#### **Acknowledgements**

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.

### **Author details**

Ziyad S. Haidar BioMAT'X (HAiDAR LAB) R&D&I, Biomedical Research and Innovation Center (CiiB), Faculties of Medicine and Dentistry, University of the Andes, Santiago, Chile

\*Address all correspondence to: zhaidar@uandes.cl; zhaidar78@gmail.com

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*Perspective Chapter: Biomimetics – Bio-Inspired Tissular Engineering for Regenerative Oral... DOI: http://dx.doi.org/10.5772/intechopen.109113*

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*Perspective Chapter: Biomimetics – Bio-Inspired Tissular Engineering for Regenerative Oral... DOI: http://dx.doi.org/10.5772/intechopen.109113*

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Section 2
