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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5881_Библиотеки_им_академика_М_И_Перельмана.pdf
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a result of its structural, mechanical, and chemical properties and similarity to articular cartilage. Many types of hydrogels like polyacrylamide, polyvinyl-alcohol,
hyaluronic acid, scaffolds, hydroxyapatite, collagen, composites of PVA-starch,
PVA-chitosan, polyethylene glycol (PEG), and so on are used as potential replacement material. These hydrogels can be subject to modication by employing diverse
paraphrastic expressions like the concentration, monomer concentration, solvent
concentration, polymerization rate, and swelling. They are the most potential candidate due to their similar hydration, mechanical, and tribological properties to the
natural articular cartilage [57].
N. Chowdhury etal.
2.5.1 Important Properties ofArticular Cartilage
Proteoglycans play vital functions in preserving the osmotic pressure, permeability,
and interstitial uid pressure of articular cartilage, as these are interconnected,
which contributes to this tissue’s distinctive mechanical and lubricating characteristics [57]. Articular cartilage mechanical property like elastic modulus ranges from 1
to 3MPa. Articular cartilage is an avascular, lubricated tissue with elevated mechanical and water content properties, featuring a compressive strength in the spectrum
of 0.53 to 1.82MPa, and a tensile strength of 17MPa [58]. The dense collagen layer
exhibits limited permeability to uids, resulting in a signicant barrier against rapid
water loss. The outermost layer of human knee cartilage demonstrated the capability to withstand the peak average stress of approximately 1.35MPa was supported
by around 74% in the outer zone and only 53% in the interfacial deeper region [53].
The anisotropic nature of articular cartilage, characterized by varying physical
properties along its depth, contributes to its versatility and adaptability across
diverse conditions [59]. The primary factor inuencing the frictional behavior
between articular cartilage surfaces is the load applied, speed, and lubrication and
the value of friction lies between 0.01 and 0.05 [60]. The natural articular cartilage
is a wear-resistant, ber-reinforced, thin, but resilient layer that is porous in nature
that hydrates the interfacial contact surface with the synovial uid, has signicant
load-bearing joints due to its stiffness, protecting the underlying bones due to proteoglycans, collagen, and high-water content water [60].
2.5.2 Scaffolds
Scaffolds are integral to regenerative medicine and tissue engineering, as they are
constructed using various materials, including synthetic and natural polymers or a
combination thereof. The scaffold’s design is aimed at emulating the properties of
the target tissue, enabling mechanical strength, enabling the controlled release of
bioactive molecules, and facilitating cell attachment. These scaffolds are indispensable in facilitating tissue reconstruction by guiding the process through chemical
2 Characterization ofHydrogel Properties intheAdvancement ofBio-Tribology
Fig. 2.12 In the domain of cartilage tissue regenerative engineering, a multitude of scaffold varieties are utilized to implement different strategies [174]
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and mechanical cues. Additionally, they act as a substrate for transporting exogenous cells and bioactive substances, further aiding in tissue growth. The advancement of sophisticated polymeric scaffolds aims to precisely direct the regeneration
process, effectively replicating the diverse characteristics inherent in natural tissues.
Demott etal. discuss some of the polymer scaffolds in detail as shown in Fig.2.12
[57]. Various techniques exist for scaffolding injectable, implant, decellularized, 3D
printed, etc. [61]. Scaffolds must have biocompatibility, high strength, compatibility
with host cells, be porous for chemical migration and cell proliferation, and be longlasting [62]. Various design parameters incorporated in the architectures of these
scaffolds, such as pore structural geometry, effective pore size, porous distribution
within the solid matrix, tortuosity, and pore accessibility in addition to porosity,
exert notable inuences on the composition, morphology, mechanical characteristics, and the operational efcacy of the newly generated cartilage tissue [65, 81,
82, 158].
Synthetic scaffolds made from poly(caprolactone) (PCL) and poly (glycolic
acid) (PGA) with identical structures demonstrate substantial variations in their
mechanical and chemical properties. As an illustration, the collective modulus of
the PCL-based scaffold was found to be 0.787MPa, while the PGA-based scaffold
exhibited a signicantly lower value of 0.173MPa [62]. Some potential natural
scaffold materials are brin, collagen, agarose, alginate, and chitosan [63]. The
trilaminar composite scaffolds were composed of PCL solution,
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1,1,1,3,3,3-hexauoroisopropanol (HFIP) as homogenous scaffolds consisting of
collagen ECM, their capacity to imitate the zone-specic organization and properties of cartilage is restricted. Trilaminar scaffolds increased the DNA content signicantly, and tri-laminar scaffolds’ enhanced compressive and tensile properties
decreased with time (5 weeks) [64]. However, cell adhesion, compatibility, and
durability with intact mechanical properties are yet to be achieved by replacing scaffolds with articular cartilage.
N. Chowdhury etal.
2.5.3 Synthetic Polymer
Some scaffolds suffer from wear debris, poor integration, and mechanical characterization which might lead to healthy surrounding tissue degradation. Eventually,
researchers focused on high water-content polymers like hydrogels that match the
characterization of articular cartilage the most. Hydrogels can be prepared with
relative ease and effectively loaded with chondrocytes, which, upon impregnation,
exhibit sustained preservation of their specic characteristics and structural properties. Poly (vinyl alcohol) (PVA), chitosan-based, gelatin-based, polyethylene glycol, polyacrylamide, PAMPS, poly (hydroxyethyl methacrylate) and its derivatives,
or DN (double network) polymers [65, 167]. Natural polymers lack stiffness in
nature [66, 163]. Through induced phase separation of solute and solvent, cryogels
and hydrogels are synthesized through freezing a solution, resulting in a polymerized solute and an inert pore-forming solvent. Upon thawing, a highly interconnected porous structure is exposed, and it is subsequently hydrated. The
cryo-polymer’s physical structural characteristics can be inuenced by compositional, internal, and external factors, including cooling rate, the degree of polymer
crosslinking, synthesis time, and solute concentration [59]. However, articular cartilage exhibits a modulus in the approximate range of several megapascals (MPa).,
and hydrogels have a ~kPa range modulus but alterations have been implemented
to enhance the mechanical robustness by introducing several networks, nanoparticles, structured mesh, polymer entanglement, charges, and so on [53, 59, 64, 108,
152, 163].
2.5.4 Polyacrylamide
Polyacrylamide (PAAm) hydrogel is a commonly used material in biological and
biomedical applications due to its tunable properties, non-toxicity, and biocompatibility. Although acrylamide, the monomer used to synthesize PAAm, is toxic,
PAAm hydrogel itself is non-toxic and safe for use [67–69]. This is because the
polymerization process of acrylamide into PAAm results in binding with a crosslinker and forming long polymer chains that are chemically inert and do not release
acrylamide monomers as shown in Figs.2.13 and 2.14. Figures2.13 and 2.14 show
2 Characterization ofHydrogel Properties intheAdvancement ofBio-Tribology
Fig. 2.13 Chemical structure of polyacrylamide hydrogel [75]
Fig. 2.14 Monomer,
crosslinker interaction of
polyacrylamide [76]
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the interaction of monomer and crosslinker with dangling bonds by altering the
mechanical properties varied by the synthesis process of PAAm. PAAm hydrogel
has high mechanical strength and elasticity, making it suitable for tissue engineering
scaffolds that require structural support. Additionally, PAAm hydrogel has relatively low toxicity and is biocompatible, enabling its use in various biomedical
applications without causing harm to cells or tissues. These features, together with
the ease of modifying the physical and chemical properties of the PAAm hydrogel,
make it a promising option for biomedical applications [70–72]. In biomedical
applications, PAAm hydrogel can be utilized for scaffolds, biosensors, tissue engineering, and drug delivery systems due to its water-retentive capacity, it can absorb,
high mechanical strength, and controllable porosity, which makes it suitable for
interacting with biological systems [68–73]. While polyacrylamide shows promise
as a potential material for biological tissue replacement, it is often composed of
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N. Chowdhury etal.
other materials like PVA, GelMA, and collagen to make articial articular cartilage.
In PVA hydrogel pores, the polymerization of acrylamide (AAm) was observed to
effectively maintain lubricity while annealing, as it prevented pore collapse and
prevented dehydration. Elevated AAm content led to enhanced water content in
equilibrium, constructed mesh size, and porosity, while concurrently reducing the
creep resistance, tear strength, coefcient of friction, and crystallinity in annealed
PVA hydrogels [74].
2.5.5 PEG Hydrogel
PEG hydrogel demonstrates substantial promise as a potential candidate for articular cartilage replacement with hydroxyl active groups due to its unique properties.
PEG hydrogel is water-soluble and biocompatible, non-toxic, non-immunogenic,
and possesses excellent water retention capabilities, resembling the natural extracellular matrix of cartilage [77]. Its adjustable mechanical properties could be customized to be consistent with the stiffness of articular cartilage, providing suitable
load-bearing support. Its properties are tunable based on pH, temperature, compositions, and so on [77, 78]. A synthetic PEG-based hydrogel has demonstrated the
capability to promote the production of cartilage extracellular matrix (ECM) constituents and maintain cell viability in Fig.2.15 [80]. It can be composed of repeating ethylene glycol units, the opening of the cyclic ether ring of ethylene oxide,
resulting in the formation of a linear polymer chain with a hydroxyl (–OH) group at
one end, another chain capped with a hydroxyl group as well. This polyethylene
glycol (PEG)-based hydrogel exhibits biocompatibility and creates a favorable
microenvironment for cell reproduction, multiplication or propagation, and growth
while promoting the generation of the essential cartilage extra-cellular matrix
(ECM) molecules as shown in Fig.2.15 [80]. Incorporating bioactive molecules,
such as growth factors, into PEG hydrogels allows for the promotion of proliferation, chondrogenic differentiation, and cell adhesion of encapsulated cells and is
used in making different types of regenerative articial tissue scaffolds as shown in
Fig.2.16 [78, 79].
PEG is a potential injectable material for articular cartilage regeneration. A PEG
hydrogel, cross-linked with a peptide originating from an aggrecans-cleavable site
in aggrecan, has been developed. This hydrogel exhibits enzyme sensitivity and has
shown promising outcomes in facilitating the regeneration of cartilage resembling
hyaline tissue while inhibiting the formation of hypertrophic cartilage [79]. The
injectability and capacity to ne-tune both mechanical and biological characteristics make PEG hydrogels more conducive to tissue regeneration potential and establish them as viable solutions for articular cartilage replacement therapies [100]. By
varying crucial parameters including molecular weight, crosslinking, polymerization time, distance, and polymer density among ester-thiol groups, it becomes feasible to control the properties of PEG hydrogel like the mechanical and structural
properties. These modications to change the properties enable the ne-tuning of
2 Characterization ofHydrogel Properties intheAdvancement ofBio-Tribology
Fig. 2.15 (a) A schematic representation of the PEG hydrogel cross-linking reaction is shown. (b)
The four-arm PEG-VS precursor polymer solution is mixed with (c) PEG-diester dithiol crosslinker at a VS/SH molar ratio of 1:1 to form a 3D hydrogel under physiological conditions [80]
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Fig. 2.16 Figure depicting a 3D-printed scaffold for cartilage regeneration, reinforced with electrospun bers, based on CDM material [78]
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N. Chowdhury etal.
the hydrogel’s characteristics, all while ensuring that the degradation and crosslinking conditions are suitable for the encapsulation of proteins and cells [80].
2.5.6 PVA Hydrogel
PVA hydrogels possess favorable biomedical characteristics, including permeability, biocompatibility, hydrophilicity, and additionally low friction and wear [60, 83].
PVA has high tensile strength and elongation before breaking, which is why it nds
extensive use in the domain of tissue regeneration, tissue adhesion barrier, and
hydrophilic coatings [84–89]. The favorable characteristics of PVA render it a
promising biomaterial contender for mimicking natural tissues, such as articular
cartilage, membrane, and tissue structure in the human organism with vinyl alcohol
converted to polyvinyl alcohol through polymerization as shown in Fig. 2.17
[90–93]. As PVA is highly water soluble, the extent of crosslinking determines the
level of uid absorption, inuencing the chemical, physical, and diffusion characteristics, and ultimately these modications inuence the polymer’s biological characteristics as shown in 19 [94, 101]. PVA hydrogel can be composed in various
techniques like physical, chemical, physiochemical, and radiation in the process
shown in Fig.2.18 [28, 101]. PVA hydrogel is combined with different types of
alloys, composites, collagen, and many other materials to increase the hydrogel’s
mechanical strength [95–98, 162].
Through the sol-gel method, by combining 20% tetra ethoxy silane (TEOS) with
PVA/Si nanocomposite, the mechanical strength of poly(vinyl alcohol) composite
material shows a notable enhancement, achieving a maximum of 35MPa [99]
(Fig.2.19).
Fig. 2.17 Vinyl alcohol structure and PVA structure [175]
2 Characterization ofHydrogel Properties intheAdvancement ofBio-Tribology
Fig. 2.18 PVA hydrogel
preparation method [101]
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Fig. 2.19 Schematic representation of typical PVA cross-linking techniques. (a) Physically cross-
linked through freeze-drying, (b) radiation-crosslinked gels through external radiation, and (c)
chemically crosslinked gels with the initiator [28]
2.5.7 Double Network Hydrogel
Double network hydrogels comprise two interconnected crosslinked polymers that
are structured through separate polymerization reactions, resulting in distinct
mechanical properties for each polymer [53]. The adjustable characteristics of DN
hydrogels, such as hysteresis, fracture energy, fracture toughness, and elastic modulus, make them a promising candidate for articular cartilage replacement, achieved
by modifying the attributes of the distinct polymer networks [102–104]. The rst
network, typically a rigid and brittle polymer, ensures structural stability and loadbearing capacity. At the same time, the alternate network which is the second network, often a soft and exible polymer, dissipates energy and enhances the overall
toughness of the material. By incorporating two networks with complementary
properties, double-network hydrogels can achieve a delicate balance between
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Fig. 2.20 Double network
hydrogel composition for
PAAm-PAMPS [178, 179]
N. Chowdhury etal.
Fig. 2.21 Illustration of double network (DN) hydrogels with various cross-linking techniques [113]
2 Characterization ofHydrogel Properties intheAdvancement ofBio-Tribology
Fig. 2.22 A synthesis scheme of the double network hydrogels with uniform chain length in the
rst network. A well-dened network structure of tetra-PEG (TPEG) gel was initially synthesized
as the rst network. Subsequently, linear polyelectrolytes (molecular stent, represented in green)
were synthesized within the TPEG gel [111]
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Fig. 2.23 PAMPS/P(NIPAAm-co-AAm) double network hydrogels were fabricated by blending a
non-thermoresponsive anionic PAMPS rst network with a thermoresponsive second network consisting of NIPAAm copolymerized with Aam [114, 115]
strength and deformability, replicating the hierarchical organization and mechanical
characteristics of natural biological tissues. Some DN hydrogels are poly-2acrylamido- 2-methylpropanesulfonic acid (PAMPS)/PAAm, PAAm/sodium alginate, PEG/PAAm, poly(N-(carboxymethyl)-N, N-dimethyl-2-(methacryloyloxy)
ethanaminium) (PCDME)/PAAm as shown in Figs. 2.20, 2.21, 2.22 and 2.23