1.

1 Introduction

The indispensable role of biomaterials in our society during the past cades has been gradually attracted
much more attentions in various ways, including the development of biomaterials not only in academic
discipline but also in industrial field. Biomaterials are derived from either synthetic or natural materials
that are used in medical technology to reorganize the functionality of damaged tissues and organs
where the interaction between biological systems and these materials have been occurring. The trend
and development of biomaterial market are determined by elements such as production cost,
compatible properties as well as biodegradable possibilities.

The global biomaterials market is estimated to reach $139 by 2022, growing at a CAGR of 11.8% from
2016 to 2022. Metallic biomaterials segment is expected to contribute significantly to the global market
revenue until 2022[2]. According to the Society for Biomaterials, there are more than 5000 scientific
journals published annually for wound care techniques and surgical devices.

This report has been focusing on the biomaterials industry which is categorized into 3 main groups
including types, applications, geographies.

1.1.1 Types:

In recent years, various kinds of metals, ceramics, polymers, and natural biomaterials are widely used in
many applications. Metallic biomaterials are further segmented into stainless steel, titanium & titanium
alloys, cobalt-chrome alloys, gold, and silver type. Polymeric biomaterials are further divided into
polymethyl methacrylate (PMMA), polyethylene, polyester, polyvinylchloride, silicone rubber, nylon,
and polyetheretherketone. Ceramic biomaterials are further segmented into calcium phosphate,
zirconia, aluminum oxide, calcium sulfate, carbon, and glass. Natural biomaterials include hyaluronic
acid, collagen & gelatin, fibrin, cellulose, chitin, alginates, and silk. The market is segmented based on
application into cardiovascular, dental, orthopedic, wound healing, plastic surgery, ophthalmology,
tissue engineering, neurological disorders, and drug-delivery systems.[2]

Metallic biomaterial segment presently dominates the global market, whereas polymeric biomaterial
segment is projected to grow rapidly during the forecast period. Metallic biomaterials are widely used in
orthopedic procedures for bone support and replacement, as they are strong and resistant to fatigue
degradation. They are used in dental, cardiovascular, and cosmetic surgeries. Moreover, metals are used
in neuromuscular stimulation devices due to their good electrical conductivity.

Orthopedic disorder is the largest application segment of the biomaterial market, owing to the increase
in the number of orthopedic surgeries using implants. Biomaterials are used for developing orthopedic
implants, which are used in various orthopedic procedures, such as orthobiologics, bioresorbable tissue
fixation products, joint replacements, spine implants, visco-supplementation, and nonconventional
modular tumor implants.[2]
 Figure [15]

1.1.2 Applications

Biomaterials are the major parts of many industries comprising of potential applications in both health
and life science fields as follows:

Tissue Engineering:

Artificial blood vessel,

Artificial kidney, etc.
 Figure [16]

Tissue engineering is one of the most important ways to achieve tissues for repair or replacement
applications. Its goal is to design and fabricate reproducible, bioactive and bioresorbable 3D scaffolds
with tailored properties that are able to maintain their structure and integrity for predictable times,
even under load-bearing conditions. Scaffolds can be applied in different tissues. It is only important to
note that it only in designing the scaffold, type of fabrication and biomaterial selection depending on the
target organ and its cells that can be affected on final application. Chemistry, architecture, porosity and
rate of degradation should provide a sufficient mechanical environment and should facilitate cell
attachment, proliferation and migration, waste nutrient exchange, vascularization and tissue ingrowth.
Also there should be a proper ratio between degradation of the scaffold and tissue ingrowth[3]

Bioelectrode and biosensors:

Bioelectrodes are sensors used to transmit information into or out of the body. Surface or transcutaneous
electrodes used to monitor or measure electrical events that occur in the body are considered monitoring
or recording electrodes. Typical applications for recording electrodes include electrocardiography,
electroencephalography, and electromyography information into or out of the body.[3]

Figure [20]
Cardiovascular:

Vascular grafts,
Heart valves.

Figure [17]

Heart valves, endovascular stents, vascular grafts, stent grafts and other cardiovascular grafts are
common medical devices in cardiovascular applications. There are several major forms of valvular heart
disease, most involving the aortic and/or the mitral valve. The most common type of valve disease and
most frequent indication for valve replacement overall is calcific aortic stenosis obstruction at the aortic
valve secondary to age-related calcification of the cusps of a valve that was previously anatomically
normal. In case of vascular pathologies, stents and vascular graft is used. Different polymers and metals
with or without coating can be applied in this category (titanium, polytetrafluoroethylene and etc).[4]

Drug Delivery System:

Controlled/sustained release of drug (Insulin, antibiotic, anticancer),

Synthetic oxygen carriers.

Figure [18]
Drug delivery systems introduced as formulations or instruments which enable to control the release
rate of a biological agent (especially a drug) in the target site. Drug delivery systems are an interface
between patient and drug. Drugs can be introduced to the organ by different anatomical routes due to
disease and drug type: Digestive system (oral, anal), oral, rectal, parenteral (subcutaneous,
intramuscular, intravenous, arterial), mucous membranes, respiratory tract by inhalation, subcutaneous
or intraosseous are man anatomical routes.[4]

Burn dressing and skin substitutes:

Wound Dressings,
Artificial skin.

Figure [19]

Skin is the largest organ that protects body from microorganisms and external forces, integrates
complex sensory nervous and immune systems, controls fluid loss, and serves important aesthetic
function. Deep skin injuries due to deep cuts, burns or degloving injuries can cause significant
physiological derangement, expose the body to a risk of systemic infection, and become a life
threatening problem. So the need of skin substitutes depending on wound depth is felt. An ideal skin
substitute must be inexpensive, long lasting, a bacterial barrier, semipermeable to water, elastic, easy to
apply, painless to the patient, non-antigenic and non-toxic and has durable shelf-time. Today a lot of
commercial skin substitutes are applied.[4]

1.1.3 Geographies

Global industrial biomaterials market has been divided into 4 major regions named US, Europe, Asia-
Pacific, Brazil and others. The Europes market reached to $8.5 billion in 2008 which occupied 33% of the
entire global market. At the same time, The US also held a crucial share of almost 11% of the worlds
market while other developed countries such as China, Korea, Japan and Russia showed a significant
growth rates.
 Figure [21]

The Asia-pacific region has been gradually playing a major role for biomedical engineering in general and
biomaterials industry in particular due to the rapidly increasing of severe accidents, diseases, and
limitations in the way of reorganizing damaged tissues. Thanks to the co-operations between Asian and
Europe countries, research activities, regional conferences, and significant revolutions in healthcare field
has been increasing rapidly.

The global biomaterials market was valued at $25.6 billion in the year 2008, and It was growing
continuously up to $83.9 billion in 2017 with the CAGR of 15%. This development is driven by more and
more huge projects were invested by governments as well as the main consumer of biomaterials.

Figure [21]
 1.2 The history of biomaterial revolutions and their impacts to biomaterial industry:

1.2.1 The first generation of biomaterials

The term Biomaterials was first attracted much attentions during the period of time from 1960s to 1970s
and this initial generation of materials was intensively studied and developed for biomedical applications
inside of human body. These efforts dedicated a huge role in the field of biomaterials. The early goals of
this field were just to maintain the mechanical properties matching with the replaced tissues or biological
systems in body and minimize the amount of toxic substances containing in material as well as reduce the
immune response toward other parts of the body.

The examples of biomaterial for the first generation as bellows:[5]

Metals (stainless and cobalt-chrome-based alloys, Ti and Ti alloys),

Ceramics (Alumina Al2O3 and Zirconia ZrO2),
Polymers (silicone rubber, acrylic resins).

1.2.2 The second generation of biomaterials

By 1984, a second revolution of biomaterials had been developed to be bioactive. Bioactive materials had
reached clinical use a variety of orthopaedic and dental applications. Various compositions of bioactive
glasses, ceramics, glass-ceramics and composites were in clinical trials[6]

Another advance in this second generation was the development of resorbable biomaterials that
exhibited clinically relevant controlled chemical breakdown and resorption. In this manner, the interface
problem is resolved, because the foreign material is ultimately replaced by regenerating tissues, and
eventually there is no more difference between the implant site and the host tissue.[7]

The improvements of first and second-generation biomaterials are limited because all synthetic
biomaterials used for repair or restoration of body represent a shortcoming. Living tissues can respond to
change physiological loads or biochemical stimuli, but man-made materials can not. This limits the life
time of artificial body parts. It also signals that scientists have reached a limit to current medical
applications. It is time to consider a shift toward better methods for the repair and regeneration of
tissues.[6]

Improvements of the use of biomaterial for second generation:[7]

Metal (All biometallic materials are non-bioactive. However, twomain approaches can be
considered to enable this property The first purpose consists of coating the surface of the metal
with a bioactive ceramic. The second one is to chemically modify the surface of the metal to
induce proteins and cell adhesion and other tissue/material interactions).
Ceramics (Bioactive glass, glass-ceramics and calcium phosphates (CaPs)).
Polymers (Biodegradable polymers of synthetic and natural origin such as polyglycolide (PGA),
polylactide (PLA).
 1.2.3 rd generation of biomaterials[6]

Third-generation biomaterials were being designed to stimulate specific cellular responses at the
molecular level. The separate concepts of bioactive materials and resorbable materials have converged.
Third-generation bioactive glasses and miroporous foams are being designed to activate genes that
stimulate regeneration of living tissues.

Two alternative routes of repair are now available with the use of these tailored biomaterials:

Tissue engineering. Progenitor cells are seeded onto modified resorbable scaffolds. The cells grow outside
the body and become differentiated and mimic naturally occurring tissues. These tissue-engineered
constructs are then implanted into the patients to replace diseased or damaged tissues. With time the
scaffolds are resorbed and replaced by host tissues that include a viable blood supply and nerves. The
living tissue-engineered constructs adapt to the physiological environment and should provide long-
lasting repair. Clinical applications include repair of articular cartilage, skin, and the vascular system,
although stability of the repaired tissues needs improvement.

In tissue regeneration. This approach involves the use of biomaterials in the form of powders, solutions,
or doped microparticles to stimulate local tissue repair. Bioactive materials release chemicals in the form
of ionic dissolution products, or growth factors such as bone morphogenic protein (BMP), at controlled
rates, by diffusion or network breakdown, that activate the cells in contact with the stimuli. The cells
produce additional growth factors that in turn stimulate multiple generations of growing cells to self-
assemble into the required tissues in situ along the biochemical and biomechanical gradients that are
present.

1.2.4 fourth generation of biomaterials:

[1]. Abridged report of the committee to survey the needs and opportunities for the biomaterials
industry

[2]. https://www.alliedmarketresearch.com/biomaterials-market

[3]. Chapter 2 Application of Biomaterials

[4] Lemons JE, Ratner BD, Hoffman AS, Schoen FJ (2013) Biomaterials science an introduction to
materials in medicine, 3rd edn. Elsevier Ltd, Amsterdam

[5]. The next generation of biomaterial development

[6]. Third-Generation Biomedical Materials

[7]. R. Langer, J. P. Vacanti, Science 260, 920 (1993).

[8].
[15]

[16]

[17]

[18] https://www.cd-bioparticles.com/l/Basic-Magnetic-Particles_20_197_0.html

[19]

[20] https://www.sensus2017.org/about/biosensing

[21] Regional analysis of the biomaterials market Nord-Pas-De-Calais and Pays De La Loire, FR South
West Germany, GE Limburg province, NL East Midlands, UK