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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5361_Библиотеки_им_академика_М_И_Перельмана.pdf
Chapter 12
Bioresorbable Composite forOrthopedics
andDrug Delivery Applications
ArbindPrasad , SudiptoDatta , SriparnaDe, PavitraSingh,
andBidyanandMahto
Abstract Metallic internal xation devices have a lot of limitations; however, it has
been considered the gold standard for xation devices. The limitations of metallic
xation are the leaching of metallic ions, stress shielding, underlying bone damage,
and heavyweight. The other problems associated are surgery after bone fracture
healing. Polymeric composites play a vital role in bone xations, scaffolds, wound
healing, and other biomedical applications. The major advantages of polymeric
composites are that they can be tailored as per the requirement, easily shaped, and
fabricated, and functional biomaterials can be mixed into certain proportions to
make them more functional and biomimetic. In this context, resorbable polymers
are widely used and also make a signicant impact or contribution to emerging
biomedical applications. A variety of resorbable polymers, such as polylactic acid,
polycaprolactone, PHB, PGA, PLA/PGA, etc., are normally used with additional
bioactive materials such as hydroxyapatite, chitosan, ceria, and other inorganic substances to have mechanical strength and also functional. In this chapter, various
domains of emerging polymeric composites will be discussed in detail, highlighting
the worthwhile applications in emerging biomedical applications.
A. Prasad (*)
Mechanical Engineering Department, Katihar Engineering College (Under Department of
Science, Technology and Technical Education, Government of Bihar), Katihar, Bihar, India
S. Datta
Department of Materials Engineering, Indian Institute of Science,
Bangalore, Karnataka, India
S. De
Department of Allied Health Sciences, Brainware University, Kolkata, West Bengal, India
P. Singh
Foundry Technology, National Institute of Advanced Manufacturing Technology (NIAMT),
Hatia, Ranchi, Jharkhand, India
B. Mahto
Government Engineering College, Vaishali (Under Department of Science, Technology and
Technical Education, Government of Bihar), Vaishali, Bihar, India
A. Kumar et al. (eds.), Applications of Biotribology in Biomedical Systems,
https://doi.org/10.1007/978-3-031-58327-8_12
327© The Author(s), under exclusive license to Springer Nature Switzerland AG 2024
328
A. Prasad et al.
Keywords Scaffolds · Implants · Resorbable polymers · Internal xations ·
Drug-eluting · Degradation
12.1 Introduction
Drugs can be delivered to the target site using efcient drug delivery systems, keeping the drug concentration within a therapeutically appropriate range. For the drug
to have the greatest benecial effect on nearby or distant healthy tissue with the
fewest adverse effects, the dose must be administered throughout the necessary
period [1–3]. Rapidly elevated blood drug concentrations occur shortly after the
dose is given in conventional systemic drug delivery, which involves intermittent
oral or intravenous administration. One issue with this kind of medication delivery
is that it can be challenging to keep the target concentration inside a constrained
therapeutic window. Patients may experience intolerable hazardous side effects if
the drug’s bloodstream concentration is too high [4, 5].
On the other hand, the medication becomes ineffective if its concentration drops
below the therapeutic range. Another problem is that medications taken orally are
metabolized rst-pass, meaning the drug concentration is signicantly decreased
before entering the bloodstream, mostly by the liver. As a result, patients may need
to get numerous doses to reach therapeutic concentrations. In the case of intravenous injections, patients may need to stay in a hospital to ensure sustained delivery
[6, 7]. When medications are administered in a regulated, localized, and sustained
way, patients may have very few adverse effects. The science of nanomedicine has
thoroughly investigated polymeric materials, of which polylactic-co-glycolic acid
(PLGA) is a leading contender in micro- and nanotechnology because of its regulated biodegradability and biocompatibility [8, 9]. For various applications, polymeric materials have grown to be quite appealing. Biomedicine is one eld in which
they are becoming more and more signicant. Polylactic-co-glycolic acid (PLGA)
is a copolymer that has been widely studied. It is biodegradable and biocompatible
and has received approval from both the European Medicines Agency and the
U.S. Food and Drug Administration [10–12]. It is offered for sale with various
copolymer ratios and molecular weights that enable the nal PLGA behavior to be
adjusted to suit a desired application. Since biomedical applications are the focus of
this review, the most attention will be paid to PLGA properties that may be helpful
in this eld. Because of its excellent water solubility, PLGA may be manufactured
in any form or size, and it offers customizable drug release. Its pharmacokinetics
and biodistribution have dose-dependent, nonlinear patterns. In general, copolymers can be produced as block or random copolymers, and in this fashion, they
exhibit various intrinsic features [13–16]. Lactic acid (LA) and glycolic acid (GA)
are often copolymerized to create PLGA, and the breakdown products of this process are harmless. Randomly distributed PLGA can typically be produced using the
previously described synthesis method in one of two ways: (i) an atactic conguration, in which the repeating units lack a regular stereochemical conguration, or (ii)
12 Bioresorbable Composite forOrthopedics andDrug Delivery Applications
a syndiotactic conguration, in which the repeating units have alternating stereochemical congurations. Sequencing is signicant because it affects how quickly
PLGA degrades; random PLGA breaks down substantially more quickly than
sequenced PLGA [17, 18].
329
12.2 Bone Fracture Statistics andtheMarket
ofBioresorbable Composite Implants
Worldwide, bone fractures are a major public health concern and a signicant nancial burden, particularly for those who have osteoporosis. Fractures are very expensive for individuals, families, societies, and healthcare systems and can result in
missed work, low productivity, disability, poor quality of life, death, and signicant
medical expenses. A meta-analysis of 113 studies yielded an estimated US$10,075
for the pooled cost of hospital treatment for a hip fracture. After a year, the total
health and social care expenditures for a single hip fracture were $43,669 globally
[19, 20]. The data on bone fractures is based on a report that THE LANCET group
published (https://www.thelancet.com/journals/lanhl/article/PIIS2666- 7568(21)00
172- 0/fulltext). Osteoporosis will cause one in two women and one in four men over
50 to shatter a bone. Bones become brittle due to this illness. People of all ethnic
origins are affected by osteoporosis. In the United States, osteoporosis-related fractures affect about two million people. Orthopedic implants are in high demand. The
need for bioabsorbable implants is growing since, as was previously said, metallic
implants have many drawbacks. According to the report (https://www.factmr.com/
report/990/orthopedic- implants- market), the global orthopedic implants market is
anticipated to reach US$ 468 million by the end of 2022. It is anticipated to grow at
a compound annual growth rate (CAGR) of 6.7% between 2022 and 2032 [21, 22].
12.3 Bioresorbable Orthopedic Implants
Because bioresorbable materials don’t react negatively to metal and metal debris, so
they provide signicant benets for the patient and the treating surgeon. The market
for orthopedic implants is expected to grow slowly in the coming years due to factors
like the high cost of the implants, the need for revision procedures every few years
based on how well the implant is holding up, and side effects related to orthopedic
implants following surgery like allergies, septic infections, and implant rejection
[23–25]. According to Health Aging.org research, osteoporosis will cause one in two
women and one in four men over 50 to shatter a bone. Bones become brittle due to
this illness. People of all ethnic origins are affected by osteoporosis—over two million individuals in the United States. The main growth drivers of the market for
orthopedic implants are the need for enhanced orthopedic implants, improvements
330
A. Prasad et al.
in surgical procedures, technological breakthroughs, and expanding patent awareness of the commercial availability of orthopedic implants. Moreover, a 4.5% cumulative annual growth rate for the orthopedic implants market worldwide is noted for
the period 2022–2027 [26, 27]. 3D printing, novel Orth biologics products, implantable smart sensor technologies, robotically assisted operations, and smart sensorenabled technologies were among the appealing potential in this area.
12.4 Bioresorbable Composites forOrthopedic Fracture
Fixation Devices
A substance that can fulll a function and then vanish from the human body is neither magic nor folklore; rather, it is supported by extensive clinical research, years
of rigorous scientic testing, and widespread commercial application. These materials, referred to as bioresorbable materials, have been used clinically for orthopedic
purposes for more than 50years. They are still used today in innovative applications
like sutures, screws, stents, scaffolds, and even synthetic skin (Figs.12.1 and 12.2).
Their ongoing progress can be ascribed to breakthroughs in creative surgical methods, processing technologies, new synthesis methods, and implant design development. As a result, there is increasing interest in the application of these materials in
patient-specic orthopedic treatments and regenerative medicine [27–30]. The need
for “biologically smart materials” is constantly growing due to factors like longer
life expectancies, more active lives, younger patient demographics, quicker healing,
sophisticated robotic surgical procedures, and lower hospitalization costs. This
requirement is satised by carefully choosing and optimizing a bioresorbable material for a particular application, which enables the implant to successfully fulll its
function invivo and to remove itself with minimal additional strain on the body’s
natural resources [31, 32] (Table12.1).
Fig. 12.1 Types of composites used in biomedical applications
12 Bioresorbable Composite forOrthopedics andDrug Delivery Applications
Fig. 12.2 Application of biodegradable polymers in xation and drug deliveries
12.4.1 Polylactides
331
Orthopedic applications are the main use for these kinds of biopolymers. In nature,
it can be reabsorbed. The advantages include the availability of numerous commercial vendors and highly processable polymers. The primary drawbacks include
restricted degradation with a very acidic breakdown. Drug delivery products and
tissue engineering are included in the application [35].
12.4.2 Poly (Ortho Esters)
It possesses pH-sensitive qualities and is controlled. Its primary purpose is in the
delivery of drugs, and its mechanical strength is weak.
12.4.3 Polyphosphoesters
These polymers exhibit exceptional biocompatibility and yield breakdown products
that are also biocompatible. The fact that synthesis is difcult is a disadvantage.
Drug delivery and tissue engineering are included in the application.
332
Table 12.1 Biodegradable polymers along with advantages and disadvantages [33, 34]
Biodegradable
polymers Polymer Advantages Disadvantages
Biobased/Natural
Polymers
Synthetic Polybutylene adipate
Polylactic acid Good processability and
thermoplastic ally
Chitin Controls weed growth Alter soil temperature and
Alginate Act as a bio-stimulant
and promotes plant
growth
Starch Abundant and cheap Brittle and low tensile
Cellulose Flexible with good
tensile strength
Polyhydroxyalkanoates
terephthalate
Polycaprolactone Flexible materials and
Poly Butylene
Succinate
Can act as a controlled
release system
Good impact resistance
and extensibility
effective in retaining
soil moisture
Good thermal stability Expensive with limited
Brittle and expensive
expensive to produce
Rips after applications
strength so it tears apart
during application
Expensive to produce on a
large scale
Expensive to produce and
lacks mechanical strength
Produces microplastics
Degrades very quickly and
has to be replenished
frequently
biodegradability
A. Prasad et al.
12.4.4 Polyphosphazenes
This kind of polymer has adjustable mechanical properties as well as synthetic exibility. The synthesis is difcult. It is typically utilized as a vaccine adjuvant and in
tissue engineering.
12.4.5 Polycaprolactone
There are numerous commercial vendors, and the polymer is highly processable.
The slow depreciation is the downside. Typically, tissue engineering and medical
devices employ it.
12.4.6 Polyurethanes
These polymers are very robust mechanically and have excellent physical stress
tolerance. Their infrequent degradation is a drawback, necessitating ester urethane
copolymerization. Tissue engineering and prosthetics are included in the application.
12 Bioresorbable Composite forOrthopedics andDrug Delivery Applications
333
12.4.7 Polycarbonates
These polymers are surface-eroding and exhibit mechanical qualities that rely on
chemistry. They require copolymerization with other polymers and exhibit low degradation. Fixators, drug delivery, and tissue engineering are all included in the application part.
12.5 Processing ofBioresorbable Composites
inOrthopedic Applications
Figure 12.3 below illustrates the general classication of biodegradable polymers.
The classication of biodegradable polymers can be done in four primary ways:
chemical synthesis, microbial synthesis, blends of biopolymers, and renewable
sources. Polyesters, poly acids, and polyvinyl alcohol (PVA) are made by chemical
synthesis. Foods like starch and chitosan come from renewable resources. Microbial
pathways are used in the synthesis of polyhydroxyalkanoates and bacterial cellulose. Starch and composite blends are also made from some biopolymer mixes
[23, 36–38].
The major polymer processing techniques followed are various technologies, as
shown in Fig.12.4.
Fig. 12.3 Classication of biodegradable polymers
334
Fig. 12.4 Polymer
processing techniques for
fabrication devices in
biomedical applications
A. Prasad et al.
12.5.1 Compression Molding
Compression molding involves heating the charge using a hot mold to polymerize
and cure (x link) the charge into the desired chapped molded plastic component.
Bringing the two pieces of the mold together compresses the spot charged. Heat is
applied via a hot mold to polymerize and cure the charge into a solidied, preshaped molded plastic component. Next, the halves are opened, and knockout pins
are pressed toward the inside to remove the molded plastic portion.
12.5.2 Transfer Molding
In the transfer molding process, the quantity of materials is calculated and added
before the molding operation. After preheating and loading the material into a pot,
the material is forced into the mold cavities via the runner system using a plunger.
When the components are placed and opened to release the part from the runner, the
mold stays closed. A higher temperature on the mold walls than where the components meet facilitates a faster ow of material through the cavities.
12.5.3 Injection Molding
Palletized ingredients are fed through a hopper into a cylinder during injection
molding, where heating coils cause the materials to melt. A nozzle is used to inject
molten thermoplastic material into the enclosed cavity. Their molding process
12 Bioresorbable Composite forOrthopedics andDrug Delivery Applications
stands out for its short cycle time (10–30 sections), translating into a very high production rate. Four steps make up the entire injection molding process: clamping,
injection, cooling, and ejection.
335
12.5.4 Extrusion
Thermoplastic plastic pellets are extruded from the hopper onto the spinning screw
in extrusion molding. The pellets melt as the screw pushes them ahead with the help
of the heaters, and the molten polymer is then driven through the shaping die under
pressure to produce the nished product. Similar to injection molding, extrusion
molding produces lengthy, homogeneous portions. To create a continuous polymer
product, the material is fed into a hopper, moved forward by a feeding screw, and
pressed through a die. The polymer is heated to melt or soften it. Thermocouples
regulate the temperature. The product that emerges from the die is referred to as
being in a water bath or blown air.
12.5.5 Blow Molding
When blow molding, hollow components of consistent thickness: During this procedure, hollow objects like bottles, spheres, etc., are created utilizing this manufacturing method. In this, air is forced into the parison, a plastic cylinder with thin
walls. Melted plastic components are forced through an extruder to create parison.
The two parts of the mold wrap around the parison, sealing it at the bottom once it
reaches a particular length. The parison is then inated with compressed air to take
the shape of the mold’s cavity.
12.5.6 Calendering Process
The plastic material is allowed to travel between the cylinder rollers during the calendering process, which creates a simple at sheet of plastic.
12.5.7 Fiber Spinning
The primary method of creating the bers is spinning, which involves extruding
polymers through a spinneret to create the bers. Tension draws the spun bers
together, creating a highly aligned chains-brillar structure.
336
A. Prasad et al.
12.5.8 Thermoforming
Thermoforming is forming thermoplastic sheets in a mold using pressure and heat.
Using a holding mechanism, the thermoplastic sheet is clamped while it is held
horizontally over the mold surface. A heating element is used to raise the sheet’s
temperature to a preset level. After being heated, the thermoplastic sheet softens and
can be stretched or pressed into the mold surface using air pressure or another
method. Additionally, there are three varieties: mechanical, pressure, and vacuum
thermoforming. This kind of method achieves incredibly adjustable sizes to the
design need. Additionally, good dimensional stability is achieved [39, 40].
12.5.9 Polymer Foaming
when foaming polymers. This process is distinguished by methods that create
microscopic bubbles inside plastic materials, which stay in place after the plastic
solidies. Another way to describe polymer foams is as closed-cell or open-cell
foams. The foam cells of closed-cell foams are separated from one another, and the
cell walls completely enclose the voids. Closed-cell foams typically exhibit superior
insulating qualities due to their reduced permeability. Cells in open-cell foams are
interconnected. Their look is softer and more pliable.
12.6 Latest Research inBioresorbable Composites
inFixation Devices
One of the most frequent injuries each year is a fractured bone, which may need a
xation device to heal properly. Metals are currently regarded as the clinical standard for bone xation devices; nevertheless, utilizing metal for xation invivo has
several unfavorable effects, such as stress shielding and metal ion leaching [41–47].
Because metals have an elastic modulus of 110–210GPa and natural bone has a
modulus of about 8–25GPa, stress shielding is caused by the use of xation materials that are stiffer than natural bone. As a result, the load is applied to the device
rather than the bone, which causes a localized decrease in bone mineral density
[37, 48–50].
In the meantime, metal ion leaching exacerbates surrounding implant inammation and discomfort. Owing to these consequences, removing the xation device
frequently necessitates a second operation, which raises medical expenses and signicantly worsens patient misery [51–56]. For these reasons, there has been a great
deal of interest in developing an entirely degradable xation device that avoids the
need for a second operation and is mechanically sound enough to assist bone healing appropriately [57–59]. Designed to be used in the creation of bone xation tools