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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5277_Библиотеки_им_академика_М_И_Перельмана.pdf
138 Bioactive Glass Materials for Biological Applications
wound healing dressings, and much more [31–35]. Bone healing is a complex process
inuenced by various factors, such as mechanical, chemical, and electrical signals.
Recent work by Polley et al. [36] demonstrated the 3D printing of bioactive and
piezoelectric barium titanate (BT) and BG scaffolds for bone tissues [37]. Recent
works by Zhou et al. [38], on the other hand, show the development of a novel
3D-printed bi-layer brain patch that promotes repair from brain injury. The tech-
nique uses high concentrations of mesoporous BG nanoparticles in the rst layer,
followed by a second layer of methacrylate silk broin hydrogel, providing the nec-
essary mechanical support. While Kohestani and Pishbin employed hydrogel-based
nanocomposite inks, consisting of alginate/gelatin matrix with mesoporous BG and
zeolite-imidazole nanoparticles for 3D printing of bone scaffolds, Hu et al. [39]
carried out melt-extrusion 3D printing to prepare biodegradable porous composite
scaffolds containing BG , calcium sulphate hemihydrate (CSH), and polylactic acid
(PLA) for bone defect repair.
3D printing has also been used for wound healing. Fayyazbakhsh et al. [40]
developed 3D-printed dressings using gelatin, alginate, and bioactive borate glass
(BBG) for the treatment of second-degree burn wounds. The inclusion of 20 wt.%
BBG enhanced mechanical properties, lowered degradation rates, and allowed for
continuous water ow for up to 10 days, solving issues with extended healing and
pain associated with standard hydrogel dressings. A 3D-printed wound dressing
was also developed by Monavari et al. [41] using an alginate dialdehyde–gelatin
(ADA-GEL) hydrogel together with astaxanthin (ASX) and BBG microparticles
(70B). Furthermore, the studies by Sánchez-Salcedo etal. [42] showed 3D-printed
mesoporous BG scaffolds with hierarchical pore structures to have higher antimicro-
bial capacity. All of these highlight the recent advances in AM for printing biological
tissues.
7.2 BIOACTIVE GLASS MATERIALS:
PROPERTIES AND APPLICATIONS
A comprehensive overview of the properties and applications of BG materials fol-
lows. The discussion encompasses their bioactivity, biocompatibility, and osteogenic
potential, highlighting their role in promoting cellular activity and tissue regenera-
tion. Properties that make them highly suitable for tissue engineering and regen-
erative medicine applications. This section provides an in-depth exploration of the
properties and diverse applications of BG materials in general.
7.2.1 Bioactivity
Bioactive glass is characterized by its ability to form a hydroxyapatite layer on its
surface when in contact with biological uids, such as blood or interstitial uid [43].
This hydroxyapatite layer mimics the composition of natural bone minerals, facili-
tating the bonding of the material with living tissues [44]. The formation of this
layer is a dynamic process involving the exchange of ions between the BG and the
surrounding environment. This bioactivity promotes osteoconduction, the growth of
bone tissue into and around the material, fostering strong and lasting integration with
139Recent Advances in Additive Manufacturing for Printing
the host bone. The hydroxyapatite layer not only enhances the mechanical stability of
implants but also accelerates the healing process by providing a biologically favour-
able environment for cell attachment and proliferation [29].
7.2.2 BiocompatiBility
Biocompatibility refers to the ability of a material to interact with biological systems
without causing adverse reactions. BG materials demonstrate excellent biocompat-
ibility, making them well suited for use in various biomedical applications. When
implanted, BG does not elicit an immune response or toxicity, ensuring that it is well
tolerated by the body. This property is crucial for the long-term success of implants
and other medical devices [45]. Moreover, BG promotes cell adhesion and prolifera-
tion, supporting the formation of new tissue. The surface properties of BG can be
tailored to encourage specic cellular responses, making it versatile for applications
ranging from bone implants to tissue engineering scaffolds. The controlled release
of ions during the bioactive process also contributes to the activation of signalling
pathways that promote tissue regeneration and healing [46].
Compared to other materials used in biomedical applications, BG stands out for its
unique combination of bioactivity and biocompatibility [37]. Traditional inert mate-
rials may lack the ability to stimulate tissue growth, while more reactive materials
might induce excessive inammation. BG strikes a balance, fostering a harmonious
interaction with the body by actively participating in the biological processes, ulti-
mately leading to improved patient outcomes and reduced risk of complications.
The precise control over the composition and structure of BG further enhances its
suitability for tailored biomedical solutions, such as patient-specic implants and
regenerative medicine approaches. This layer facilitates osseointegration and pro-
motes bone regeneration. Furthermore, BG materials exhibit excellent biocompat-
ibility, minimizing adverse immune responses and facilitating cell adhesion and
proliferation.
7.2.3 osteoGenic potential
One of the hallmark features of BG materials is their osteogenic potential [45]. BG,
with its inherent osteogenic potential, has emerged as a promising material for pro-
moting bone regeneration and integration in biomedical applications. The unique
composition of BG, which is also tailorable, facilitates the formation of a hydroxy-
apatite layer upon contact with biological uids, mimicking the mineral structure of
natural bone. This bioactivity not only enhances the material’s osseointegration but
also stimulates osteogenic activity. The released ions, such as silicon and calcium,
play a pivotal role in activating signalling pathways that promote the differentia-
tion of osteoprogenitor cells into osteoblasts, the cells responsible for bone forma-
tion. This activation of osteogenic processes accelerates the healing of bone defects
and supports the successful incorporation of BG implants within the host tissue.
Furthermore, BG scaffolds, manufactured using advanced AM techniques, provide
3D structures conducive to cell attachment and proliferation, fostering a favourable
microenvironment for new bone tissue formation. The osteogenic potential of BG
140 Bioactive Glass Materials for Biological Applications
positions it as a versatile and effective material in regenerative medicine, particularly
in orthopaedic and dental applications where bone healing and integration are criti-
cal for long-term success.
7.2.4 controlled release of Bioactive ions
Bioactive glass materials can be engineered to release bioactive ions such as calcium,
silicon, and phosphate ions, which play crucial roles in tissue regeneration processes,
as already discussed in the above section. The controlled release of these ions from
the glass matrix promotes angiogenesis, stimulates cell proliferation, and enhances
tissue remodelling at the site of implantation [47]. Figure7.1 depicts the application
of bioglass using controlled release of bioactive ions.
7.2.5 versatility in formulation and processinG
Bioactive glass materials offer versatility in formulation and processing, allowing
for customization to meet specic application requirements [2]. They can be syn-
thesized using various techniques, including sol-gel processing, melt-quenching,
and spray-drying, enabling precise control over composition, morphology, and sur-
face properties. Customization of implants in accordance with the needs of the
patient is also possible with AM technology, where control over the scaffold pro-
cessing on the porosity can be advantageous for cell attachment, regeneration of
tissue, and molecular movement. The personalization also allows the integration of
drug delivery by controlled release of therapeutic agents, which shall be discussed
subsequently.
FIGURE7.1 Depicting the prospects of controlled release of bioactive ions [48]. Under CC
license
141Recent Advances in Additive Manufacturing for Printing
7.2.6 applications in tissue enGineerinG
The unique properties of BG materials make them well-suited for a wide range
of tissue engineering applications. They are commonly used as scaffold materials
for bone regeneration, dental implants, and cartilage repair [49]. Additionally, BG
nanoparticles are incorporated into hydrogels and composite materials to enhance
their bioactivity and mechanical properties [50].
3D-printed BG varieties have shown tremendous promise in bone tissue engineer-
ing, addressing challenges in bone defects and fractures. Customized implants and
scaffolds, created through AM, offer precise control over the architecture and porosity
of the structures. For instance, a BG scaffold designed with a composition like 13-93
provides an excellent framework for cell attachment and bone regeneration [51]. The
scaffold acts as a temporary support, gradually degrading over time and being replaced
by newly formed bone tissue. This approach has been applied in cases of critical-sized
bone defects, trauma, or orthopaedic surgeries, facilitating enhanced bone healing and
integration.
In the eld of dentistry, 3D-printed BG materials have found applications in
creating patient-specic dental implants, crowns, and bridges (Field [52]). The ability
to precisely tailor the composition and structure of BGs allows for the development
of dental implants that promote osseointegration and exhibit favourable biomechani-
cal properties. This is particularly benecial in cases of tooth loss or dental trauma
arising from accidents, where the customization of implants ensures optimal t and
functionality. BG compositions, such as those containing strontium or zinc, may also
contribute to improved dental implant outcomes by promoting bone regeneration and
preventing bacterial infections [53].
Bioactive glass varieties, especially those designed for tissue engineering applica-
tions, are being explored for cartilage regeneration. 3D printing techniques enable
the fabrication of scaffolds with specic porosity and mechanical properties con-
ducive to cartilage growth [54]. By incorporating BG with tailored compositions,
researchers aim to create implants that can support chondrogenesis and integrate
seamlessly with the surrounding cartilaginous tissue. This approach holds promise
for addressing cartilage defects, osteoarthritis, and other joint-related issues, offering
a potential solution for improving joint function and reducing pain in patients. BG
materials, when 3D printed into porous structures, have been investigated for their
application in wound healing and skin regeneration. These scaffolds can support the
attachment and proliferation of skin cells, facilitating the regeneration of dermal tis-
sue [55]. The controlled release of ions from BG may also contribute to antibacterial
properties, reducing the risk of infections in chronic wounds. This approach holds
the potential for treating burns, chronic wounds, and skin injuries, providing a sup-
portive matrix for tissue regeneration and minimizing scarring.
7.2.7 druG delivery systems
Bioactive glass materials serve as effective carriers for the controlled release of thera-
peutic agents such as growth factors, antibiotics, and anti-inammatory drugs [56]. The
porous structure of BG scaffolds facilitates drug loading and release, enabling localized
142 Bioactive Glass Materials for Biological Applications
delivery to the target tissue while minimizing systemic side effects [56]. The versatility
of preparing the formulations allows the customization of drugs based on the patient’s
specic needs, including the case of delivery of strontium or zinc ions to enhance the
regeneration, which provides an enhanced therapeutic efcacy, especially in the case
of bone-related disorders and in post-surgical recovery. The drug delivery system inte-
grated into the BG-based implants also allows targeted delivery at the site, aiding in
immediate treatment strategy, ensuring a localized release of drug for reducing inam-
mation or to prevent bacterial infection. Bacterial infections of even the minute degrees
are to be completely prevented with the possible comorbidities that can cause and even-
tually lead to the need for the consumption of antibiotics. Consumption of antibiotics is
also to be reduced, foreseeing the patient’s health condition, which would be impaired,
and the emerging antibiotic resistance exhibited by the microorganisms [57]. Thus, an
antibacterial environment within the implant aids in a complete recovery process.
7.2.8 antiBacterial properties
Certain formulations of BG materials exhibit inherent antibacterial properties, mak-
ing them promising candidates for combating implant-associated infections. The
release of bioactive ions disrupts bacterial cell membranes and inhibits microbial
growth, contributing to improved implant success rates and patient outcomes [58].
Different BG compositions incorporate various antibacterial ions, and a compara-
tive analysis sheds light on their efcacy in preventing infections. For instance,
45S5 Bioglass, enriched with sodium (Na) ions, has demonstrated antimicrobial
activity against a broad spectrum of bacteria, including Staphylococcus aureus,
Staphylococcus epidermidis, and E. coli [59]. S53P4glass ceramic, which incor-
porates silver (Ag) ions, exhibits potent antibacterial effects and is commonly uti-
lized in orthopaedic and dental applications (Field [60]). In contrast, BGs containing
zinc (Zn) ions, such as those used in the 13-93 composition, showcase antimicrobial
capabilities while also promoting tissue regeneration [61]. The choice of antibacterial
ions inuences the spectrum of pathogens targeted and the duration of antimicrobial
activity. While silver ions are broadly effective, zinc ions contribute to both antibac-
terial and tissue-regenerative properties. Understanding the nuanced differences in
antibacterial ion incorporation allows for the strategic selection of BG compositions
tailored to specic biomedical applications, where preventing infections is a critical
factor in the success of implants and regenerative therapies.
Overall, BG materials represent a versatile platform with immense potential for
advancing regenerative medicine and tissue engineering. Their unique combination
of properties makes them indispensable for a wide range of biomedical applications,
from bone regeneration to controlled drug delivery systems. Continued research and
innovation in BG materials hold promise for addressing complex clinical challenges
and improving patient care outcomes.
7.3 INTEGRATING BIOACTIVE GLASS WITH
ADDITIVE MANUFACTURING
The core of this chapter explores recent advances in integrating BG materials with
AM technologies. It discusses advancements in material formulations, printing
143Recent Advances in Additive Manufacturing for Printing
techniques, and post-processing strategies aimed at enhancing the bioactivity and
structural integrity of printed tissues. BG is a type of glass that bonds with living
tissues, encouraging bone regeneration and healing when implanted in the body [49].
The integration of AM and BG creates novel opportunities for the creation of per-
sonalized scaffolds, implants, and medical equipment with improved bioactivity and
specic characteristics. This section explores recent developments and strategies for
incorporating BG into AM processes:
7.3.1 material formulation and optimization
In the realm of AM, the formulation of BG materials plays a critical role in deter-
mining printability, mechanical properties, and bioactivity. Researchers are actively
exploring novel compositions and processing techniques to tailor BG formulations
for specic printing applications. BGs often contain silicon, calcium, and phosphorus
oxides, as well as other trace elements that promote bone repair and tissue integration
[62]. Polymers, ceramics, and other materials in the nanoscale that are compatible
with the AM process may be considered additives [45].
7.3.2 printaBility and scaffold desiGn
Additive manufacturing enables the precise fabrication of complex tissue scaffolds
with customizable architectures. BG’s printability and scaffold design with AM
entails streamlining the manufacturing process to create intricate structures with
precise mechanical strength, porosity, and bioactivity [63]. In order to optimize
printing settings for uniform deposition and layer adhesion, it evaluates elements,
including nozzle diameter, printing speed, and layer thickness. Reinforcements or
additives to improve printability, mechanical strength, and biological responsive-
ness, such as polymers, ceramics, or nanoparticles. BG materials can be 3D printed
into intricate scaffold designs that mimic the native extracellular matrix of target
tissues [64]. Techniques such as fused deposition modelling (FDM), stereolithog-
raphy (SLA), and selective laser sintering (SLS) offer precise control over scaffold
geometry and porosity. Table7.1 shows the various techniques employed for 3D
printing of biotissues.
7.3.3 surface modification and functionalization
Surface modication techniques are employed to enhance the bioactivity and
cell-interaction properties of BG scaffolds [65]. Functionalization with bioactive
molecules, growth factors, or peptides promotes cell adhesion, proliferation, and
differentiation, facilitating tissue regeneration processes. Improved surface quali-
ties of printed structures are necessary for surface modication and functionaliza-
tion of BG via AM. This improves bioactivity, biocompatibility, and interaction
with biological tissues. Modifying printing parameters or post-processing methods
is done to impart surface roughness to the surface of BG objects at the micro- or
nanoscale [28]. To encourage cell adhesion and tissue integration, thinly coating
the surface of printed BG scaffolds with bioactive chemicals or biomolecules is
also done.
144 Bioactive Glass Materials for Biological Applications
7.3.4 incorporation of Bioactive Glass nanoparticles
Bioactive glass nanoparticles combined with additive printing present a viable way
to create innovative biomedical devices, implants, and scaffolds that have improved
mechanical and bioactive capabilities. BG nanoparticles are increasingly utilized
as additives in composite materials for AM. Advanced biomaterials with custom-
ized qualities and functionalities for orthopaedics, dentistry, tissue engineering, and
regenerative medicine can be created by combining BG nanoparticles with AM. This
method has a lot of potential for producing customized implants and medical equip-
ment that encourage quicker healing and better clinical results. Their high surface
TABLE7.1
Description of the techniques
Printing
technique Description Diagram
Material jetting Entails utilizing a print head to deposit
bioactive glass material droplets onto the build
substrate. By precisely controlling the mix and
distribution of materials, this approach makes
it possible to create hybrid constructions with
desired properties.
Binder jetting It uses a binder to layer-by-layer selectively
link bioactive glass particles together. This
method works well for printing complex
geometries, and it can be mixed with different
materials to give the nished printed objects
certain characteristics.
Nozzle based
deposition
This method involves extruding bioactive glass
material through a nozzle and depositing it
onto the build surface. It allows for material
selection freedom and allows for the creation
of multi-material structures with customized
properties for a range of biomedical
applications.
145Recent Advances in Additive Manufacturing for Printing
area-to-volume ratio and bioactivity augment the mechanical properties and osteo-
genic potential of printed scaffolds [52]. Nanoparticle incorporation strategies aim to
improve BG dispersion and homogeneity within the matrix [66].
7.3.5 post‑processinG and surface finishinG
Post-processing techniques such as sintering, annealing, and surface polishing are
employed to optimize the mechanical and bioactive properties of printed constructs.
Heat treatments promote densication and crystallization of BG, enhancing its
mechanical strength and bioactivity [67]. Surface nishing methods improve scaf-
fold biocompatibility and minimize surface roughness, facilitating cell attachment
and tissue ingrowth. BG’s surface layers can be selectively removed by chemical etch-
ing using acids or alkaline solutions, resulting in textured or roughened surfaces that
encourage tissue integration and cell adhesion [68]. It is possible to adjust etching
parameters, including solution concentration, temperature, and time, to get the required
surface shape and bioactivity [69]. Ion-exchange solutions can be used to alter the sur-
face chemistry of printed BG structures in order to improve their bioactivity [30]. Ion
exchange processes have the ability to introduce ions into the glass surface, such as
strontium, calcium, or phosphate, which can stimulate osteogenic activity and promote
the production of apatite. These surface nishing and post-processing methods allow
us to improve the performance, quality, and usefulness of BG structures made with
AM, which makes them suitable for use in a range of biomedical applications like scaf-
folds, implants, and medical equipment. Recent innovations integrating BG materials
and critical ion release proles in bioprinting technologies showcase remarkable prog-
ress towards realizing complex, viable tissue constructs, and organoids for regenerative
medicine and pharmacological applications as shown in Figure7.2.
FIGURE7.2 Image depicting the advances in achieving biomedical prospects by the inte-
gration of bioactive glass also aided by essential ions
146 Bioactive Glass Materials for Biological Applications
7.3.6 multi‑material printinG and hyBrid constructs
Advances in multi-material printing enable the fabrication of hybrid constructs
comprising BG materials and other biocompatible polymers or ceramics. Various
materials can be deposited concurrently or sequentially using multi-material printing
techniques, including material jetting, binder jetting, or nozzle-based deposition [70].
With the use of these procedures, hybrid structures can be precisely controlled in
terms of material distribution and composition. Gradually switch between materials
to attain desirable gradients in stiffness, porosity, or bioactivity for tissue engineering
or regenerative medicine applications. Through the utilization of hybrid constructs
and multi-material printing, we may design novel biomedical devices, implants, and
scaffolds that exhibit improved functionality and performance [71]. These methods
make it possible to create tailored solutions for medication delivery, tissue engineer-
ing, regenerative medicine, and personalized healthcare.
7.3.7 in vitro and in vivo evaluation
The integration of BG with AM necessitates rigorous in vitro and in vivo evalua-
tion to assess scaffold biocompatibility, bioactivity, and tissue regeneration potential.
Preclinical studies involving cell culture assays, histological analysis, and animal
models provide valuable insights into scaffold performance and guide translational
research efforts. In vitro, assessment examines the cytocompatibility of BG scaf-
folds by culturing appropriate cell types on the scaffold surface, such as mesen-
chymal stem cells and osteoblasts. It uses assays like MTT, Alamar Blue, or live/
dead staining to measure the morphology, proliferation, and viability of the cells
[72]. Using microscopy methods like scanning electron microscopy (SEM) or uo-
rescence microscopy, it assesses cell adherence and dissemination on BG surfaces
[73]. In vitro evaluation also analyses cellular interactions with the scaffold mate-
rial and analyses cell shape, focal adhesions, and cytoskeletal architecture. In vivo
assessment examines implantation studies in animal models (e.g., rats, rabbits, sheep)
to evaluate the biocompatibility and tissue response to BG scaffolds. It assesses host
tissue integration, inammation, and immune response following implantation using
histological analysis and immunohistochemistry [74]. Monitoring bone regenera-
tion and remodelling around implanted BG scaffolds using imaging techniques such
as X-ray, micro-computed tomography, or magnetic resonance imaging. Quantify
bone formation, defect healing, and scaffold degradation rates to evaluate the effec-
tiveness of the scaffold in promoting tissue regeneration. Evaluating the long-term
biocompatibility and safety of BG scaffolds by monitoring host responses and tissue
interactions over extended periods. Assess potential adverse effects, such as chronic
inammation, brosis, or foreign body reactions, to ensure the stability and compat-
ibility of the scaffold in vivo [75].
Overall, the integration of BG materials with AM holds immense promise for
the development of advanced tissue engineering scaffolds with enhanced bioactivity
and functionality. Continued research efforts are aiming to optimize printing param-
eters, rene scaffold design strategies, and elucidate the mechanistic basis of tissue-
material interactions for future clinical translation.
147Recent Advances in Additive Manufacturing for Printing
7.4 CHALLENGES AND FUTURE DIRECTIONS
Bioglass can be used as substrates for cells to support themselves since they can
attach to living bone and soft tissues. Adopting bioglass materials for bioprinting
successfully, however, presents a number of difculties. Cell survival and function
may be jeopardized by the severe processing temperatures required to melt and shape
bioglasses into print-ready inks. More delicate techniques for preparing bio-ink are
needed. Second, under some conditions, tissue maturation processes may be ham-
pered by poor bioglass dissolving rates brought on by subpar paste chemistries.
Optimizing ion release and degradation proles to bolster cellular proliferation is
still an unresolved research concern. Furthermore, the intentional building of com-
plicated developmental paradigms required to mimic genuine tissue microstructures
is hampered by our inadequate understanding of how bioglass surface reactions
guide cell destiny processes. Enhancing architectural control may be elucidated by
developments in high-resolution cell imaging and analysis during bioglass-supported
cultures.
Up the future, bioglass AM presents intriguing opportunities for customized tis-
sue implants with geometries that are therapeutically relevant for lling up bone
deciencies or supporting soft tissues that require restoration. We anticipate that
advancements in multi-paste bioprinting will provide advanced compositional and
microstructural control, enabling the creation of bioglasses that direct in vitro vascu-
larization and innervation processes to maintain viability before implantation.
Furthermore, combining bioprinting with cutting-edge nanofabrication tech-
niques may allow for precise topographical and biochemical patterning to guide stem
cell development along certain lineages within printed tissues. Adoptive transfers
of cells conditioned in this manner in vitro may help address host rejection prob-
lems, provided that immunological consequences are carefully taken into account.
Bioglass provides special capabilities for quickening the translation of bioprinted
tissues; nonetheless, to fully realize their potential, more fundamental research,
along with supporting engineering advancements in print head technologies, bio-ink
compositions, and multi-material control, is required.
7.5 CONCLUSION
Using cutting-edge multi-material 3D bioprinters, additive biomanufacturing pro-
vides ground-breaking potential for producing functioning, live tissue structures
for medical applications and disease simulation. However, overcoming signicant
obstacles that current technologies are unable to address completely is necessary to
realize the transformative medical potential of bioprinting. The current state of the
art is not yet able to produce sustainable, higher-order tissues that replicate natural
organ complexity due to difculties with vascularization, innervation, biocompati-
bility, and controlled resorption rates. Moreover, regulatory advancement is hindered
by vagueness in standards and benchmarks.
Nonetheless, the topic shows great potential as it quickly accumulates syner-
gies across crossing elds like materials science, stem cell biology, microuidics,
imaging, biomechanics, and machine learning. Combined progress in enhancing