Journal of Zhejiang University-SCIENCE A (Applied Physics & Engineering) 2023 24(11):1027-1042

www.jzus.zju.edu.cn; www.springer.com/journal/11582
E-mail: jzus_a@zju.edu.cn

Review
https://doi.org/10.1631/jzus.A2200403

Biomaterial types, properties, medical applications, and other

factors: a recent review
Reeya AGRAWAL1,3, Anjan KUMAR1, Mustafa K. A. MOHAMMED2*, Sangeeta SINGH3
1
VLSI Research Centre, GLA University, 281406 Mathura, India
2
Radiological Techniques Department, Al-Mustaqbal University College, 51001 Hillah, Babylon, Iraq
3
Microelectronics & VLSI Lab, National Institute of Technology, Patna 800005, India

Abstract: Biomaterial research has been going on for several years, and many companies are heavily investing in new product
development. However, it is a contentious field of science. Biomaterial science is a field that combines materials science and
medicine. The replacement or restoration of damaged tissues or organs enhances the patient’s quality of life. The deciding
aspect is whether or not the body will accept a biomaterial. A biomaterial used for an implant must possess certain qualities to
survive a long time. When a biomaterial is used for an implant, it must have specific properties to be long-lasting. A variety of
materials are used in biomedical applications. They are widely used today and can be used individually or in combination. This
review will aid researchers in the selection and assessment of biomaterials. Before using a biomaterial, its mechanical and
physical properties should be considered. Recent biomaterials have a structure that closely resembles that of tissue. Anti-
infective biomaterials and surfaces are being developed using advanced antifouling, bactericidal, and antibiofilm technologies.
This review tries to cover critical features of biomaterials needed for tissue engineering, such as bioactivity, self-assembly,
structural hierarchy, applications, heart valves, skin repair, bio-design, essential ideas in biomaterials, bioactive biomaterials,
bioresorbable biomaterials, biomaterials in medical practice, biomedical function for design, biomaterial properties such as
biocompatibility, heat response, non-toxicity, mechanical properties, physical properties, wear, and corrosion, as well as biomaterial
properties such surfaces that are antibacterial, nanostructured materials, and biofilm disrupting compounds, are all being
investigated. It is technically possible to stop the spread of implant infection.

Key words: Surface severe plastic deformation (SSPD); Hyaluronan (HA); Extracellular matrix (ECM); Polyvinylchloride
(PVC); Tissue engineering (TE)

1 Introduction et al., 2019, 2020; Ahmed et al., 2020; Al Rugaie et al.,

2022; Alhujaily et al., 2022). Biomaterials are used in
A biomaterial is any matter surface or construct many ways in medical practice in medical implant
that interacts with biological systems. They can be de‐ methods to promote the healing of human tissues, re‐
rived from nature or synthesized in the lab using me‐ generated human tissues, molecular probes, nanoparti‐
tallic components, polymers, ceramics, or compos‐ cle biosensors, and drug delivery systems. Examples
ite materials. The study of biomaterials just like baby of medical implants include but are not limited to
and biomechanics is a multi-disciplinary field that heart valves, stent grafts, artificial joints, ligaments,
has established disciplines in medicine, chemistry, tendons, hearing loss implants, and dental implants.
chemical engineering, mechanical engineering, biome‑ Examples of regenerated human tissues include scaf‐
dical engineering, and materials science (Mohammed fold cells and bioactive molecules. Because biomateri‐
als restore function while speeding recovery, today pa‐
* Mustafa K. A. MOHAMMED, mustafa_kareem97@yahoo.com tients suffering from accidents or illnesses benefit sig‐
Mustafa K. A. MOHAMMED, https://orcid.org/0000-0002-1850- nificantly from using biomaterials (Saadatmand et al.,
6355 2021; Jasim et al., 2022; Vakil et al., 2022). Using bio‐
Received Aug. 19, 2022; Revision accepted Nov. 2, 2022; engineered materials to repair wounded tissue or re‐
Crosschecked Jan. 5, 2023; Online first Mar. 2, 2023 store a compromised biological function in medical ap‐
© Zhejiang University Press 2023 plications is expected. Historically, ancient Egyptians
1028 | J Zhejiang Univ-Sci A (Appl Phys & Eng) 2023 24(11):1027-1042

first employed biomaterials, which used sutures made (Yilmaz et al., 2019; Motameni et al., 2021; Alshem‐
of animal sinew to repair wounds. Among other medi‐ ary et al., 2022b). Everything that can be used instead
cal, biological, physical, and chemical domains, tissue of living things is called biomaterial. There are many
engineering and materials science have had a more different biomaterials, which are natural and artificial
significant recent impact on the contemporary field of materials. The biological material is made by a living
biomaterials than any of these disciplines combined thing, like skin or an artery. Fig. 2 shows biomaterials
until recently (Mohammed et al., 2020; Mahmood required for tissue engineering of salient features.
et al., 2022; Noori et al., 2022). The use of non-living
materials and living cells in biomaterials can be com‐
bined. Engineers can create molded or machined parts,
coatings, and fabrics for biomedical devices and other
consumer goods and industrial applications using these
materials. Depending on the category, many medical
devices may be included. They typically decay fast in
the body after completing their intended function;
some are even bioabsorbable (Ahmed and Moham‐
med, 2020; Ahmed et al., 2020; Govindan et al., 2022).
Biomaterials can be divided into two categories: thera‐
peutic materials and diagnostic materials. Fig. 1 shows
different types of biomaterials.

Fig. 2 Salient features of biomaterials required for tissue

engineering

1.1 Bioactivity
Bioactivity is the ability of a biomaterial to make
a person’s body do something good for the material’s
job and efficiency (Alshemary et al., 2022a, 2022c).
When materials are implanted in the body, the term
osseoconductive conductor refers to materials that
work as osseoconductive conductors. It can be found
in bioactive glasses and ceramics. Most importantly,
the materials used in implanted bone stimulate bone
growth while also breaking down the body’s fluids.
When hydroxyapatite forms on the surface of bioma‐
terials, it is common to find out how good they are for
humans (Qin et al., 2021). Fig. 3 shows the different
Fig. 1 Types of biomaterials impacts of biomaterials.
1.2 Self assembly
Therapeutic biomaterials are used in medical de‐
vices to treat or improve the function of tissues in the In the scientific community, the phrase “self-
body. Biomaterials used in tissue repair or replace‐ assembly” is frequently used to describe the phenome‐
ment replace lost or damaged tissue because of injury non in which particles spontaneously assemble with‐
or disease. Biomaterials can be looked at with terms out the assistance of an external force (Jin M et al.,
that are both biological and engineering. Trauma, dis‐ 2021). Massive clusters of these particles can com‐
ease, and degeneration can lead to surgery to fix bine to create one of seven crystal systems that are
things, which can happen if needed. People with thermodynamically stable and structurally well-defined
broken bones usually need to have them replaced in metallurgy and mineralogy. A well-known fact is
 J Zhejiang Univ-Sci A (Appl Phys & Eng) 2023 24(11):1027-1042 | 1029

Fig. 4 Biomaterials’ applications

disc forms a seal to prevent blood from returning. Du‐

Fig. 3 Different impacts of biomaterials Pont used polyethylene terephthalate in the valve’s
manufacture because it was a commercial material for
that molecular self-assembly is used to develop many
their pyrolytic carbon coating (Indurkar et al., 2021).
biological structures, including the human body. Using
The company employed a woven fabric called Dacron
natural microstructural features and designs to pro‐
to hold the coating against the surrounding tissue. The
duce mechanically superior biomaterials has become valve can be absorbed into the body while allowing
increasingly popular (Książek, 2021). The use of self- tissue growth around it using a mesh.
assembly is becoming increasingly prevalent in chem‐
ical synthesis and nanotechnology. Applying these 1.3.2 Skin repair
strategies can result in a diverse range of well-ordered
It is possible to employ artificial tissue cells in
structures. Molecular and liquid crystals are only a
extreme conditions where using a patient’s cells might
few instances of cutting-edge technology to realize
cause irreversible damage to the patient’s body (Chen
the same. These approaches are distinct because they
et al., 2021). Developing a structure on which cells
rely on self-organization to achieve their goals. can create and organize themselves is challenging. The
1.3 Applications scaffold must meet several characteristics, including
biocompatibility, cell adhesion, mechanical strength,
Before they may be used in therapeutic settings, and biodegradability. Copolymers of lactic acid and
biomaterials must demonstrate that they are biocom‐ glycolic acid are helpful as scaffolds.
patible with the human body (Castro et al., 2021).
Any biocompatibility difficulties must be resolved be‐ 1.3.3 Bio-robots and 4D bio-printing
fore the product is commercialized. As a result, novel Bio-robots are an emerging field at the intersec‐
pharmacological treatments are subjected to the same tion of biomedical engineering, cybernetics, and ro‐
stringent standards as biomaterials. Therefore, all man‐ botics, to create innovative tools for merging the bio‐
ufacturing organizations must ensure that all of their logical and mechanical worlds to improve communi‐
products are traceable to discover any more inappro‐ cation, modify genetic information, and create ma‐
priate materials that may have been added to the batch. chines that mimic biological processes. 4D bio-printing
Various biomaterials are employed in the following is a next-generation additive manufacturing-based
fields, as shown in Fig. 4. fabrication process that has applications in creating
1.3.1 Heart valves both soft and stiff tissue structures and biomedical
devices (Yu et al., 2021). Incorporating their biomedi‐
During a back-and-forth motion between two cal expertise, the 4D bio-printing community has made
semi-circular discs, blood flow occurs while the other remarkable achievements in producing innovative
1030 | J Zhejiang Univ-Sci A (Appl Phys & Eng) 2023 24(11):1027-1042

stimuli-responsive polymeric materials in recent years. external magnetic field, their rheological and me‐
Cartilage, bone, heart, and neurological tissue are all chanical properties alter. MRFs are well-known for
part of this category, as are the expensive biomedical their severe stress amplification in a magnetic field,
equipment used to administer drugs. When external while MREs well-known for their modulus altera‐
magnetic or electric fields are applied, a particular class tions (Bastola et al., 2020). However, MREs have a
of stimuli-responsive materials known as magneto/ relatively short history as a counterpoint to MRFs.
electro-responsive polymers (MERPs) is activated. After initial studies on MREs were conducted, a novel
Regulation of MERPs (multifunctional, dynamic, and class of MR materials called MR plastomers (MRPs)
fast reversible characteristics) is achieved at various has the potential to create intelligent materials and
length scales (Wu et al., 2020). structures distinct from MREs and MRFs. The highly
mobile magnetic particles give MRPs plastic proper‐
1.4 Bio-design
ties even at room temperature and have more sub‐
Unmet clinical requirements can only be ad‐ stantial MR effects than MREs. MRPs are unsuit‐
dressed via innovation. Worldwide, medical devices able for vibration isolators and absorbers due to their
and implants are in great demand, with India being meager beginning moduli. But MRPs have the po‐
the most prominent market. Medical technology inno‐ tential as a package for elastic, flexible, and conduc‐
vation is needed today, more than ever, to address tive sensors and actuators like on/off switches. MREs
local problems and bring about lasting solutions (Yu experience dynamic changes in stiffness, natural fre‐
et al., 2021). The recognition of the need to encourage quency, and damping capacity in response to an ap‐
and promote indigenous affordable medical innova‐ plied magnetic field. Supplies classified as multi-role
tions has taken steps to establish med-tech innovation equipment (ME) can be used in various situations and
bio-design initiatives and capacity for creative medi‐ are highly versatile. Changes in behavior, such as a
cal technology research prototyping, validation, and shift in modulus or stiffness, are less prevalent (Dargahi
testing. The main goal is to develop innovative, low- et al., 2019).
cost medical implants and technology for the benefit Consequently, there has been an explosion of re‐
of the whole nation. The bio-design goals are shown search investigating MRE behavior concerning attri‐
in Fig. 5. bute changes in the past few years. MEs alter their be‐
havior by changing stiffness, natural frequency, damp‐
ing capacity, storage/loss modulus, and complicated
viscosity. Sandwich beams and vibration absorbers/
isolators are only two examples of technical applica‐
tions that benefit from ME’s malleable stiffness and
modulus.

Fig. 5 Bio-design objectives 1.6 Improved 3D-printed biomaterials for tissue

engineering
1.5 Magnetorheological
Additive manufacturing (AM), often known as 3D
Innovative materials include magnetorheological printing, has made it possible to create patient-specific
(MR) substances, which change their rheological and scaffolds, medical devices, and multiscale biomimetic
mechanical properties in reaction to an external mag‐ structures with intricate cytoarchitecture and a hierar‐
netic field. Gels, liquids, and elastomers with solid chy of function and structure (Arif MM et al., 2021;
consistency are viable for MR materials. Magnetorhe‐ Arif ZU et al., 2022). The demand for 3D-printed re‐
ological fluids (MRFs) and magnetorheological elas‐ placement organs is rising with the number of people
tomers (MREs) are the most popular MR materials. needing transplants. Many researchers in tissue engi‐
At MREs, the magnetic particles are immobilized in a neering (TE) are currently focusing on 3D printing be‐
precisely controlled location within a polymeric ma‐ cause of its potential to revolutionize the field. Both
trix, whereas in MRFs, the particles float in a carrier polylactide and polycaprolactone have attracted con‐
fluid like silicone oil (Moreno et al., 2021). In an siderable interest as potential biomaterials for tissue
 J Zhejiang Univ-Sci A (Appl Phys & Eng) 2023 24(11):1027-1042 | 1031

regeneration due to their superior physicochemical by new tissue, a process known as resorption (such
and biocompatibility. Biodegradable polymers’ in‐ as bone). Other bioresorbable compounds include
teractions with in-vivo and in-vitro testing methodolo‐ polylactic–polyglycolic acid copolymers, tricalcium
gies for future evaluation of degradation and biologi‐ phosphate [Ca3(PO4)2], and polylactic–polyglycolic
cal properties are also highlighted (Mondal et al., acid copolymers. Other typical materials employed in
2016). Biomedical engineers will be of greater use to recent decades include calcium oxide, calcium carbon‐
the clinical community if they bear the above in mind. ate, and gypsum.
2.2 Biomaterials in medical practice
2 Biomaterial classifications, biomaterials in Several applications for biomaterials in medicine,
medical practice, and biomaterials designed research, and bioengineering, including the following,
for function are shown in Fig. 6. It is one of the main reasons bio‐
materials are used. They replace hard or soft tissues
Artificial implants can produce a range of reac‐ damaged or destroyed by the disease. Most people’s
tions in the tissue once implanted. Tissue reacts to the tissues and structures last for a long time, but they can
implant’s surface and determines how the implant in‐ be damaged by fractures, infections, and cancer (Jin S
teracts with the surrounding tissues. The majority of et al., 2021).
the time, a biomaterial can be defined or classed in Orthopedics: Biomaterials are used in many ways,
three ways based on the tissues’ responses (Bhattacha‐ but orthopedic implant devices are the most common.
ryya et al., 2021; Momin et al., 2021; Saydé et al., Osteoarthritis and rheumatoid arthritis change the
2021; Wang F et al., 2021; Hayajneh and Al-Oqla, structure of joints that can move freely, like the hip,
2022).
knee, shoulder, ankle, and elbow.
2.1 Biomaterial classifications Cardiovascular applications: Heart valves and ar‐
teries can have cardiovascular circulatory problems.
2.1.1 Bioinert biomaterials Implants can be used to fix these problems.
The materials that are not harmful to the body Ophthalmics: The tissues in the eye can get sick
after they are put inside the body are stainless steel, from many different things, making it hard to see and
titanium, alumina, zirconia, and ultra-high molecular eventually leading to blindness. Cataracts, for exam‐
weight polyethylene, among other things. Bioinert ma‐ ple, cause the lens to become cloudy. If users do not
terials have minimal contact with the body’s surround‐ want this, users can get a synthetic (polymer) intraoc‐
ing tissue after being transplanted into the body. A ular lens instead.
bioinert implant’s biological usefulness depends on Dental applications: People with bacteria in their
how well it can work with its tissue. A fibrous capsule mouths can quickly kill their teeth and the gums that
can form around non-bioinert implants. hold them in place. People with dental caries, which
are holes in their teeth caused by plaque’s metabolic
2.1.2 Bioactive biomaterials activity, can lose a lot of teeth.
Bioactive implants and the body fluids surround‐ Wound healing: There were first sutures, and they
ing them undergo an ion-exchange process, which cre‐ were used to close wounds. Implantable biomaterials
ates an implant-surface layer composed of carbonate can be traced back to this time. It is common for syn‐
apatite (CHAp), which is physiologically active and thetic sutures to make polymers, but some metals can
has a mineral-equivalent carbonate composition. In also make stitches.
terms of chemical composition and crystallographic
2.3 Biomaterials designed for function
structure, this layer is analogous to the mineral phase
of bone in the human body. Bioengineers evaluate the performance of a bio‐
material’s properties, depending on how well it per‐
2.1.3 Bioresorbable biomaterials
forms a particular activity and how it will be used
As soon as they enter the body, bioresorbable ma‐ (Bonferoni et al., 2021; Janarthanan and Noh, 2021;
terials dissolve (resorb) and are eventually replaced Liu et al., 2021; Yeung and Kelly, 2021). New skin
1032 | J Zhejiang Univ-Sci A (Appl Phys & Eng) 2023 24(11):1027-1042

leaking in the weeks and months following surgery

(Roach et al., 2021). The procedure uses laser-heated
nanoscale materials, gold rods inserted in a matrix,
and photothermal nanocomposites.
A burn bandage dissolves in the mouth: Burn
sufferers experience excruciating pain when removing
the application. The current clinically authorized dress‐
ings cause stress to newly produced tissue, making a
recovery more difficult to achieve (Tao et al., 2022).
Because of the controlled decomposition of the hydro‐
gel into safe by-products, on-demand dressing removal
and re-exposure of the wound will be achievable with‐
out mechanical debridement or cutting, making thera‐
py more straightforward and less unpleasant.
Zinc alloy stents that disintegrate in body acid-
metal stents are routinely utilized to maintain the pa‐
tency of blood arteries. Long-term complications asso‐
ciated with metal stents include vessel re-narrowing,
blood clots, and bleeding, among other complica‐
Fig. 6 Biomaterials in the medicine fields tions (Kumar et al., 2022). A bioabsorbable zinc stent
that gradually dissolves can reduce the hazards asso‐
and blood vessel growth are essential for wound heal‐
ciated with long-term stent use. Early research on
ing to function correctly and quickly.
zinc stents that dissolve in the body has shown their
Intriguing fibrous protein systems: Stem cells are
potential.
unspecialized; they can differentiate into any cell. Bio‐
materials can influence the behavior and fate of stem
cells (Holmes et al., 2022). These materials must regu‐
3 SEM/TEM materials used for bio-applications
late biological activity, including stem cell produc‐
tion, by simulating the flexibility of different tissues.
Three cutting-edge technologies, biomaterials,
Protecting the lungs with a chest bandage: Ap‐ may have a bright future shortly (Hasan et al., 2021;
plying biomaterial sealants and patches to injured Wang YM et al., 2021; Nickkholgh et al., 2022). Bio‐
tissue makes it possible to rejuvenate and restore it. materials injected into the body deliver medicines, ge‐
Brown algae-derived alginate could be utilized as a netic information, and proteins. Fig. 7 shows scanning
lung leak sealant and therapeutic patch to treat pneu‐ electron microscope (SEM) images, transmission elec‐
monia and cystic fibrosis (Nace et al., 2021). Accord‐ tron microscope (TEM) images, and modes of four
ing to the manufacturer, alginate is administered to nanocrystals.
the wound after freeze-dried and rehydrated with Researchers are developing injectable biomateri‐
bodily fluids. Preliminary data reveal that this patch als containing synthetic and naturally occurring com‐
effectively treats lung leakage and repairs lung tissue ponents to treat cancer and heart disease. Biomaterials
in mice. A clever wound dressing can effectively treat based on supramolecular chemistry have several bene‐
diabetic ulcers in the long run. Many people wear wrist fits over conventional molecular ones when treating
bandages with embedded sensors and actuators that injury and illness (Ackun-Farmmer et al., 2021). Sur‐
come into direct contact with their flesh (Morita et al., rounding the development of supramolecular biomate‐
2021). It is anticipated to improve healing while rials that may imitate natural biological signaling or
simultaneously lowering the number of hospital visits respond to physiological stimuli, scientists are exam‐
and dressing changes patients require. Laser technology ining how to make them. SEM can be used to demon‐
is used in laser-aided tissue healing and laser welding. strate that the polymer blend is monophasic. The sur‐
Approximately one-quarter of persons who have had face got more abrasive, and the number of holes pro‐
their colon segments re-joined experience wound site duced increased (Fig. 8, NaOH).
 J Zhejiang Univ-Sci A (Appl Phys & Eng) 2023 24(11):1027-1042 | 1033

Fig. 7 SEM images, TEM images, and modes of four nanocrystals (Li et al., 2018): (a) SEM images; (b) TEM images;
(c) selected area electron diffraction (SAED) patterns for the four micro/nanocrystal structures product models derived
from SAED and crystal parameters. Reprinted from (Li et al., 2018), Copyright 2018, with permission from American
Chemical Society

Fig. 8 SEM images of polyhydroxybutyrate (PHB) and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx)

films before and after lipase and NaOH hydrolysis. Reprinted from (Zhao et al., 2002), Copyright 2002, with permission
from Springer Nature

Numerous bacteria produce enzymes released a polymer chain on its surface. The material disinte‐
outside their cell walls, such as extracellular polyhy‐ grates layer by layer (surface erosion, not inside the
droxybutyrate (PHB) depolymerase. The enzymes polymer matrix). SEM pictures of PLA and its compos‐
initially adhere to the surface of polymer materials via ites after 14 d in compost and mud are shown in Fig. 9.
their C-terminal substrate-binding domains. They then Polylactic acid (PLA) and its composites’ surface
use their N-terminal catalytic regions to degrade poly‐ morphology changed. All of the polymer materials
mer chains (Adorinni et al., 2021; Sivasankarapillai examined exhibited biodegradation. Composites of
et al., 2021). Enzymes can cleave specific segments of PLA and starch (50: 50) exhibited more alterations
1034 | J Zhejiang Univ-Sci A (Appl Phys & Eng) 2023 24(11):1027-1042

Fig. 9 PLA and PLA/starch samples before they were broken down (a and b), after they were broken down in compost
(c and d), and in soil for 14 d (e and f). Reprinted from (Wilfred et al., 2018), Copyright 2018, with permission from
Innovation Info

than pure PLA samples (Ma et al., 2021). While starch

was removed from the surface of the PLA mixes,
chemical hydrolysis was selected for the breakdown
of pure PLA. Things degraded more rapidly in com‐
post than in soil. Energy-dispersive X-ray spectros‐
copy (EDS) detector can ascertain whether any addi‐
tives have a detrimental effect on the deterioration
process. Different PLA/polybutylene adipate tere‐
phthalate (PBAT) blends containing the same PLA
may degrade at varying speeds due to thickness vari‐
ances and commercial additives added during produc‐
tion (Xiang et al., 2021).
The results indicate that the talc components may
Fig. 10 SEM-EDS micrograph of PLA/PBAT. Reprinted
not behave as expected when water exposure, altering from (Musioł et al., 2018), Copyright 2018, with permission
their degradation rate. from Elsevier
EDS analysis of some PLA/PBAT blend com‐
ponents revealed the presence of white inclusions 4 Biomaterials’ limitations and uses
(Mg and Si) in the polymer matrix, which was derived
from a commercial addition known as hydrated mag‐ Biomaterials look promising new treatment op‐
nesium silicate (talc), illustrated in Fig. 10. Phase sep‐ tions in the early phases of research, but their full po‐
aration occurs in low-miscibility mixes, whereas high- tential has not yet been realized. Biomaterials have
miscibility blends have a smooth surface. The molar various restrictions on interacting with the patient’s
mass and crystallinity of PLA and polyhydroxyalkano‐ bodily fluids (Crist et al., 2021; Dziadek et al., 2021;
ates (PHAs) in polyester blends such as PHB and poly Zhang et al., 2021). Despite this, there are significant
(hydroxybutyrate-valerate) (PHBV) affect their ability differences between synthetic materials and biological
to operate well together (González et al., 2021). When tissues, which suggests that biomaterials may not be
the component molar masses are large, the combina‐ as effective in healing wounded tissue as they could
tions are not correct. In this case, one of the blend otherwise be. Biomaterials used in the heart must con‐
components has a lower molar mass, reducing the tract in sync with the heartbeat to avoid cardiac prob‐
likelihood of phase separation. lems. Another biomaterial problem that influences
 J Zhejiang Univ-Sci A (Appl Phys & Eng) 2023 24(11):1027-1042 | 1035

heart health is insufficient oxygen reaching the heart.

Because biomaterials have only been able to restore a
fifth of the heart’s original size, a significant heart at‐
tack causes more damage to the organ than it can heal
with them. Researchers will develop novel biomateri‐
als for treating additional illnesses after understanding
the underlying reasons. It is necessary to create better
methods to ensure new medicines repair damaged or‐
gans and tissues while not hurting patients during de‐
velopment. More details can be found in the electronic
supplementary materials (ESM).

5 In vitro cytotoxicity concept in biomaterials

Biomaterials that work well with cells and tissues

need to be designed and used in a way that works for
them. One way to see how cells and tissues respond is
to measure how toxic a substance is to a cell in the Fig. 11 Twenty-four hours after seeding, extracts were either
added to a cell monolayer that was not yet fully grown (the
lab or how harmful it is to a cell in the real world
first mode) or added to cells that had just been thrown
(Nouri et al., 2021; Salihu et al., 2021). Cell toxicity around (2nd mode). Reprinted from (Jablonská et al., 2021),
is measured by how many cells die or cannot grow. It Copyright 2021, with permission from Nature Publishing
has been shown to meet these needs. There are two Group
ester groups on each side of the carbon-carbon double
bond in polypropylene fumarate (PPF), so there are
two on each side. The unsubstituted carbon bond on
the fumarate functional group makes PPF cross-link
(Chu et al., 2021). Fumaric acid and propylene glycol
are the products of hydrolysis, which breaks down an
ester bond. Fig. 11 shows how the two methods of ex‐
tracts were used. They were either added to a cell
monolayer still growing 24 h after seeding or to cells Fig. 12 Toxicity of bioceramic materials in vitro and vivo.
floating in water (2nd mode). Reprinted from (Thrivikraman et al., 2014), Copyright 2014,
with permission from The Royal Society of Chemistry.
5.1 Evaluation of bioceramic toxicity RBC: red blood cell

Different kinds of artificial implants made of tests to ensure that materials are safe for people. In
metals, ceramics, polymers, and composites are safe the long run, if a biomaterial that has not been ade‐
for people to have in other body parts, depending on quately tested is implanted, it may cause a long-term
where they are put. Ceramics are the most common biological reaction (Ma et al., 2022). The biomaterials
material used to repair hard tissue that has been dam‐ used in an implant must be checked for risks to last a
aged (Kumari and Chatterjee, 2021; Sadowska et al., long time in the body. Table 1 describes the classifica‐
2021). Because different tests must be done depend‐ tion of biocompatible polymer optical fiber.
ing on how long the material is in contact with the
5.1.1 Cytotoxicity
body to ensure it is biocompatible. Fig. 12 shows how
bioceramic materials are tested in vitro and how they Plant a cell or put the cell in a solution from ex‐
can be harmful. tracting the material to determine how a specific cell
Biocompatibility is very important for any mate‐ type reacts to a particular material. Choosing the right
rial used in the body, so regulatory bodies have set up cell lines, controls, biochemical assay type, and culture
1036 | J Zhejiang Univ-Sci A (Appl Phys & Eng) 2023 24(11):1027-1042

Table 1 Classification of biocompatible polymer optical fiber for people to have in their bodies for a long time.
Category Material They can get into the cytoplasm of a eukaryotic cell
Multifunctional PC, COC, CPE because they are tiny (Park KM et al., 2022). In one
Natural materials Silk, cellulose case, zirconium oxide particles that came out of bone
cement when worn down are an exception to this rule.
Elastomers PDMS, POC-POMC
It has been said that when these nanoparticles get in‐
Hydrogel PEG, PEGDA, PAAm
side the body, they can make reactive oxygen species
Synthetic PLA, PGA, PLGA, PLLA
(ROS) and make the body more oxidatively stressed,
PC: polycarbonate; COC: cyclic olefin copolymer; CPE: conductive but this is not true. It can also cause other signaling
polyethylene; PDMS: polydimethylsiloxane; POC-POMC: poly (oc‐
tamethylene citrate)-poly (octamethylene maleate citrate); PEG: poly pathways to be activated, leading to the aberration
(ethylene glycol); PEGDA: poly (ethylene glycol) diacrylate; PAAm: or double-strand breaks of chromosomes in the nu‐
polyacrylamide; PGA: poly (glycolic acid); PLGA: poly (lactic-co-
glycolic acid); PLLA: poly (L-lactic acid)
cleus, affecting cell division and growth. Different
gene regulatory proteins are turned on in other cells
time all play a significant role in whether a material when a virus damages a cell. It can happen when on‐
can be used with other things. On cell lines from mice, cogenes are turned on or tumor suppressor genes
humans (and other animals), the toxic residues from do not work (Abreu et al., 2022). A tumor can start
three polymeric biomaterials did not make any differ‐ when these things happen. If biomaterials can cause
ence in how sensitive the cells were to them. More cancer, relevant in vitro methods should be used to
evaluation methods and specific cell lines should be see if this is the case. Tiny particles of cadmium, co‐
used (Park SY et al., 2022; Suvindran et al., 2022; balt, cobalt-chromium alloy, and nickel have been
Szczuka et al., 2022). Tissue osteoblast and keratino‐ found to cause cancer in people who use orthopedic
cyte cell lines can also be used to check the cell com‐ implants. These metals are used in many types of
patibility of orthopedic implant materials. Wound dress‐ orthopedic implants. Biomaterial implants’ toxicity
ing materials can also be tested for their cytotoxicity, and long-term stability can be tested more effectively
which can be done with different types of cells. For a and in biologically relevant ways. Even though com‐
new biomaterial to move from the lab to the clinic, it paring the biocompatibility results of new mate‐
must undergo rigorous tests, as shown in Fig. 13. rial in vitro and in vivo can show its safety, its true
fate will only be known when used in people (Liu
et al., 2022). Fig. 14 shows possible ways that nano‑
particles and micron particles enter the body and cause
genotoxicity.

Fig. 13 Formation steps of biomaterials from bench side

to bedside. Reprinted from (Thrivikraman et al., 2014),
Copyright 2014, with permission from The Royal Society
of Chemistry

5.1.2 Genotoxicity
Fig. 14 Genotoxicity representation. Reprinted from (do
Implant materials and particles that come with Nascimento et al., 2017), Copyright 2017, with permission
them are a big part of figuring out how safe they are from Springer Nature
 J Zhejiang Univ-Sci A (Appl Phys & Eng) 2023 24(11):1027-1042 | 1037

6 Conclusions and future directions drugs. The chemical and biological characteristics re‐
stricting medicine delivery are still a mystery, so kineti‐
Biotechnology could improve people’s health and cally controlling the release of medicines remains a
quality of life if used correctly. This procedure could challenging problem (Xu et al., 2021). Over 50 years
provide compounds of extensive utility. Utilization pos‐ of encapsulation and release materials have been de‐
sibilities are vast due to the molecular and atomic com‐ veloped to release bioactive pharmaceuticals over a
binations. Biomaterials with this technique may be used long period and (in the best case scenario) begin inter‐
in various fields, including medicine, dentistry, veteri‐ actions with the host to control how much medication
nary care, and even mechanical engineering. Fabricat‐ is taken from the capsule. While conventional chemi‐
ing biosensors, drug delivery systems, and scaffolds cals like silver nanoparticles or silver nitrate have
are a few of this technique’s possible uses. The ability demonstrated biocidal activity against human patho‐
to accurately adjust stoichiometry and particle size gens (both gram-negative and positive) and bacteria
during production is possible. From their early days, resistant to quaternary amine, lignin-derived nanopar‐
when they were used by surgeons performing amaz‐ ticles have shown biocidal activity at significantly
ing surgeries with the aid of engineers, the areas of bi‐ lower silver concentrations, resulting in an inactive bio‐
ology and bioengineering have come a long way. Just degradable particle after release, which has less of an
as a wide range of materials can be utilized to make effect on the environment (Kalirajan et al., 2021). An
biomaterials, so can their medical applications. Bio‐ immobilized (or “spatially restricted”) catalyst is con‐
materials can be used to create replacement heart tained in lignin colloidal particles. The research will
valves and other organs for patients needing repair. Use emphasize the design, characterization, and potential
it on items that can move, like the hydroxyapatite- uses of nanostructured lignin hydrogels. No investiga‐
coated hip implant from 20 years ago. The medical tions into drug release or biocompatibility have been
device industry heavily uses biomaterials because of carried out despite the idea that carriers play a role in
their pivotal role in the healthcare system. Products medication delivery. During the precipitation step, the
for hard and soft tissues, biomedical devices, pharma‐ researchers added the hydrophobic insecticide Aver‐
ceuticals, test kits, and more can all be found in the mectine to the particles and examined the microparti‐
medical sector. However, there is still a long way to cles for drug release and ultraviolet (UV) protection,
go. Biomaterials used in modern medical therapies, among other properties (Wan et al., 2021).
such as those for preventing and treating major heredi‐
6.2 Tissue engineering scaffolds
tary diseases, may vary in response to new medical
needs. We can expect a surge in the popularity of metal, An interdisciplinary approach is taken while
ceramic, and polymer implants for medical use. Re‐ looking into the various biomaterials utilized in tissue
searchers in molecular biology, biochemistry, genet‐ engineering and regenerative medicine. Scaffolds can
ics, and physics are merging their efforts to develop be used for multiple purposes, some of which are at
more effective biomaterials for specific applications. odds with one another (Rashid et al., 2021). If harm‐
Biocompatibility, bioactivity or surface reactivity, ful degradation products are to be avoided, scaffolds
biodegradability, stabilizability, good mechanical and for bone regeneration must be disintegrated and re‐
physical features, manufacturability, low weight, af‐ placed with natural bone. Allogeneic bone transplants
fordability, and accessibility are all traits to look for in are the second most common source of replacement
a material. Molecular and genetic approaches to dis‐ bones, behind the chin, retro-molar area, iliac crest,
ease research have led to exciting new developments and trabecular bone (available from bone banks). In
in diagnosis, treatment, and prevention. A biomaterial addition to allogeneic and xenogeneic transplants, there
is any synthetic material that could be used in medi‐ are also xenogeneic and alloplastic transplants (which
cine. For instance, a biomaterial heart valve replace‐ use materials like hydroxyapatite or tricalcium phos‐
ment could be passive or active. phate). Patients can now receive treatments specifically
suited to their needs because of advancements in stem
6.1 Drug encapsulation and release gels and hydrogels
cell technology. A variety of factors influence biocom‐
Much interdisciplinary research has been con‐ patibility (Khalid et al., 2021). These include long-
ducted on biomaterials used in the administration of term stability against physiological media, mechanical
1038 | J Zhejiang Univ-Sci A (Appl Phys & Eng) 2023 24(11):1027-1042

strength depending on the application’s mechanical therapy of the future. Cells, 11(1):43.
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Ackun-Farmmer MA, Overby CT, Haws BE, et al., 2021. Bio‐
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plication. Comprehending the adhesion mechanisms Current Opinion in Biomedical Engineering, 19:100308.
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Applied Sciences, 11(6):2490.
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Author contributions vitro degradation and bioactivity of antibacterial chromium
Reeya AGRAWAL: conceptualization, methodology, data doped β-tricalcium phosphate bioceramics. Ceramics–
curation, writing-original draft; Anjan KUMAR: conceptual‐ Silikáty, 66(3):347-353.
ization, review, and editing; Sangeeta SINGH: supervision and Arif MM, Khan SM, Gull N, et al., 2021. Polymer-based bio‐
validation; Mustafa K. A. MOHAMMED: supervision. materials for chronic wound management: promises and
challenges. International Journal of Pharmaceutics, 598:
Conflict of interest 120270.
https://doi.org/10.1016/j.ijpharm.2021.120270
Reeya AGRAWAL, Anjan KUMAR, Mustafa K. A.
Arif ZU, Khalid MY, Zolfagharian A, et al., 2022. 4D bio‐
MOHAMMED, and Sangeeta SINGH declare that they have
printing of smart polymers for biomedical applications:
no conflict of interest.
recent progress, challenges, and future perspectives. Reac‐
tive and Functional Polymers, 179:105374.
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