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Biomaterials
Biomaterials are noviable materials designed to interact with living systems
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Biomaterials are typically made of metals, polymers or
ceramics
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Biomaterials may
also incorporate biological materials such as proteins, cells, and matrix materials
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Interactions at the biosurface between the material and tissue
over time predicts the success of the biomaterial
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To be viable a biomaterial must demonstrate biocompatibility, the ability of a material to
perform with an appropriate host response in a specific application/ the ability of materials to
locally trigger and guide normal wound healing, regeneration and tissue integration
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Device compatibility is governed by international standards (ISO)
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The tests to be performed varies
depending on type of device, contact type, and time in body
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ESRD is expensive to treat and has a high mortality rate
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Haemodialysis is used to treat ESRD whilst patients are awaiting a
transplant
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Whilst
haemodialysis improves symptom control, it fails to improve survival rates
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These molecules can only be removed by adsorption
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, et al
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Recent advances in carbon technology have allowed the development of a
novel phenolic resin derived activated carbon, which can be used uncoated (increases
adsorptive capacity) for direct contact with blood and has a tailored nonporous structure
allowing adsorption of larger biological toxins above 50kDa
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Such monoliths may be used in haemodialysis,
inserted into the dialyser cartilage allowing removal of uraemic toxins from the patients blood
by adsorption
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In vitro monolith recirculation studies revealed a significant reduction in IL-6
concentration after filtration through nanoporous monoliths
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High concentrations of IS and PCS were
detected in haemodialysis patient blood samples prior to dialysis
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However, perfusion of
the post high flux haemodialysis patient blood samples through nanoporous carbon
monoliths significantly decreased the concentration of IS and PCS in comparison to a
control
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No significant changes in blood chemistry occurred
following monolith filtration, with the exception of creatinine
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The other exception was total protein, tota; protein levels
dropped below normal range when compared to the control group
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No significant difference in fibrinogen concentration was detected
in the carbon monolith filtration samples when compared to the controls, showing the
monolith is not impacting the clotting cascade
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Further work is necessary to develop and assess a scaled
up drive that can be used in conjunction with a dialysis circuit
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although there may be some removal of beneficial
molecules in equivalent molecular weight range, replacement is possible through normal
homeostatic mechanisms
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Meng, F
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, 2018
The wearable artificial kidney can deliver continuous ambulatory dialysis for more than three
million patients with ESRD
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Two-dimensional titanium carbide (MXene) with the composition of Ti3C2Tx, where Tx
represents surface termination groups, can absorb urea, due to its layered structure,
reaching 99% removal efficiency from aqueous solution and 94% from dialyte
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The biocompatibility of Ti3C2Tx and its selectivity for urea absorption from dialyte
open a new opportunity in designing a miniaturised dialyte regeneration system for a
wearable artificial kidney
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, et al
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Such graphene nanoparticles can then be used as
hemoperfusion adsorbents for the treatment of sepsis or CKD
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The primary causative agents of liver diseases include;
alcoholic liver disease, non-alcoholic fatty liver disease caused by obesity, viral infection by
hepatitis B and C viruses, inborn errors of metabolism, and autoimmune disease
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The liver has
great regenerative capacity, 70% loss of function is survivalable for regeneration of function
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Gut derived nutrients are delivered to the liver via portal circulation
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The lover has the capacity to recruit and activate immune cells in response to
gut-derived metabolites or pathogen derived signals
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Bile acids produced by the
liver can also modulate the microbiome as some bacteria utilize bile acids
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Increased alcohol consumption can disrupt the intestinal epithelial barrier and result
in increased gut permeability which is a major factor in alcoholic liver disease
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Alcohol
consumption is associated with alterations in gut microbiome and the disbalance of
pathogenic and commensal organisms in the intestinal microbiome may contribute to
abnormal gut-liver axis in alcoholic liver disease
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The most common underlying
mechanisms of bacterial infections in patients with cirrhosis is abnormal bacterial
translocation
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These alterations may
lead to migration of bacteria/ bacterial products to either the systemic circulation of the
mesenteric lymph node, causing a wide range of clinical manifestations including
hemodynamic instability, high proinflammatory cytokine levels, development of severe or
recurrent infections, acute-on-chronic liver failure, hepatic encephalopathy, hepatorenal
syndrome and poor prognosis
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The portal vein
is an additional source of blood, bringing nutrient- and antigen-rich blood from the

gastrointestinal system to the liver
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Kupffer cells, which are phagocytic cells, are found within or below the
fenestrated sinusoidal endothelium and extend their processes into the sinusoids
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In the space of Disse (the space just below the
endothelium), there are other stromal cells, including satellite cells and antigen-presenting
dendritic cells
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Biliary canaliculi are located
between two cords of cells on the contralateral side of the sinusoids
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The portal triad
consists of the portal vein, hepatic artery and bile duct
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Satellite cells
are involved in vitamin A storage and fibrotic response to damage leading to the formation of
scar tissue
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Functional liver replacement is required following liver decompensation as a result of; acute
liver failure (ALF) due to paracetamol overdose, alcohol poisoning or viral infection, or
acute-on-chronic liver failure (ACLF) due to alcohol, sepsis, or viral hepatitis
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There are several limitations regarding
liver transplant, including; donor shortage, both living and deceased donors are eligible
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Due to these limitations alternative treatment options are needed to bridge patients
with ALF or ACLF to either recovery or transplant
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Standard dialysis, used in
the treatment of renal failure, only removes small water soluble molecules failing to remove
albumin bound and high molecular weight toxins, and, as most liver toxins are albumin
bound, dialysis is not an effective treatment for liver failure
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Non-biological liver support devices utilise albumin dialysis for detoxification, extracorporeal
devices clean blood of endogenous toxins following liver failure
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Biological liver support is a tissue engineering approach to return
detoxification, synthetic, and metabolic function
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Non-biological liver support devices
- Evenepol, et al
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Due to the relatively small pore size of the
high flux membranes used, passage of large albumin molecules is hindered, while
smaller compounds diffuse freely through the membrane
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The albumin-rich dialysate is then regenerated in a separate circuit by using low-flux
dialysis and a different adsorber to wash away or to bind to toxins unloaded from
albumin
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The dialysate is then passed through a column of uncoated activated charcoal to
remove hydrophobic molecules, and is then passes through a second column with an
anion exchanger resin adsorber
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To overcome the issues of the MARS system and to increase detoxification efficacy
the prometheus (PROM) system was developed
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First, albumin is separated
from blood by a novel capillary albumin filter (AlbuFlow), which is permeable to
albumin and hence albumin bound substances
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Finally , after
passage through the AlbuFlow, the patient's blood is dialysed through a high flux
dialyzer whereby water-soluble toxins are eliminated
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A significant decline in the serum level of water soluble and protein bound toxins was
achieved by both the MARS and PROM systems in this study
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The superiority of the PROM system
is most likely due to direct contact of the toxin loaded albumin with the high affinity
adsorbing material within the secondary circuit of the PROM device
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Some symptomatic
improvement has been demonstrated in sub-group cohorts
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Bioartificial liver devices
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Jalan
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, 2003

In a bioartificial device, isolated cultured hepatocytes are then incorporated into
bioreactors
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Approximately 150-450g of cells (or 10^10
hepatocytes), providing the function of 10-30% of normal liver function mass, are
required to support a failing liver
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Primary porcine hepatocytes are the most used
in the liver support systems that have been evaluated in clinical trials, such as the
HepatAssist BAL (bioartificial liver) device
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Concerns remain
regarding immune reactions to forgein antigens, as well as xenozoonosis in the form
of cross species infection with porcine endogenous retrovirus
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Plasma can be separated, warmed, oxygenated in the secondary circuit before being
perfused through the bioreactor capillaries
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While most toxins and transport proteins
can pass through, larger substances like immunoglobulins, complements, viruses,
and cells, cannot
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The HepatAssist BAL also
incorporates two caracol columns in the circuit prior to the bioreactor for removal of
toxins, which could damage or impair the function of the pig hepatocytes
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Hepatocytes remain in the extracapillary space
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The AMC-BAL incorporates a siraly wound polyester matrix sheet
that induces an integral hollow fibre compartment for xogenation
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In ALF patients treated with porcine
hepatocytes based on BAL, neurological improvements and minimal reduction of
serum bilirubin and arterial ammonia have been observed
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The ELAD uses the C3A hepatocyte line, a subclone of the HepG2 hepatoblastoma
cell line
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In a recent randomised controlled phase I trial in
patients with fulminant hepatic failure, there was a significant advantage for patients
receiving liver transplantations in the ELAD group[
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The only adverse effect noted
was transient hypotension
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Primary challenges fr BALs include the maintenance off enough oxygenated,
metabolically active, functional hepatocytes over time to bridge transplant or
restoration of liver function, and the maintenance of hepatic phenotypic
characteristics, such as; ammonia detoxification, elimination of bile/bilirubin, protein
synthesis, and immunological removal of bacterial products
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Hepatocyte transplantation
-

Lee
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, 2016
Hepatocyte transplantation (HT) is emerging as a promising alternative to orthotopic
liver transplantation (OLT) in patients with inborn errors of metabolism eg
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HT may be cheaper and less invasive than OTL with
short term restoration of function
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Hepatocytes are generally infused into the portal venous system,
from which they migrate into the liver cell plates of the native organ
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Transplanted hepatocytes produce and release tissue factor, which
activates the coagulation pathway, leading to the formation of thrombin and fibrin
clots
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Inflammatory cells
including granulocytes, monocytes, kupffer cells, and natural killer cells cluster
around transplanted hepatocytes leading to their rapid clearance shortly after
transplantation
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Effective inhibition of instant blood-mediated
inflammatory reaction would improve hepatocyte engraftment, proliferation, and
function
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, et al
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local environment factors induce hepatocyte homing, differentiation,
and proliferation
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Thus, a three
dimensional native live ECM would support the viability, phenotype, function, and
tissue assembly of hepatocytes
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This study decellularized porcine livers to generate liver constructs
as a scale that can be clinically relevant
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Furthermore, isolated hepatocytes
are engrafted and reorganised in the porcine decellularized liver using a human sized
organ culture system
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Ophthalmic biomaterials
The eye
The eye is the primary sense organ providing visual information about the surrounding
environment
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Photochemical receptors convert photonic stimuli into neural
impulses
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Globally the number of people of all ages visually imparied is estimated to be 285 million, of
whom 39 million are blind
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Cataracts are the primary cause of blindness, cataracts are surgically treatable,
however, in developing countries such surgical skills aren't available
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The outermost coat of the eyeball, the fibrous layer, is composed of dense avascular
connective tissue, it consists of the sclera and the cornea
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The sclera protects and shapes the eyeball and
provides an anchoring site for the extrinsic eye muscles
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The cornea allows light to enter the eye and is
responsible for light refraction
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The external
sheet, a stratified squamous epithelium protects the cornea from abrasion
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The vascular layer forms the middle coat of the eyeball and consists of the
choroid, ciliary body and the iris
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Its dark brown pigment, produced by melanocytes,
absorbs light, preventing it from scattering and refracting within the eye
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The round central opening of the iris,
the pupil, allows light to enter the eye
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The innermost layer of the
eyeball is the retina
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The posterior

segment of the eye is filled with a clear gel called vitreous humor
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The iris divides the anterior segment into the
anterior chamber (between the cornea and the iris) and the posterior chamber (between the
iris and the lens)
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Aqueous humor
supplies nutrients and oxygen to the lens and cornea, and it carries away metabolic waste
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Aqueous humor
drains via a trabecular meshwork into the canal of schlemm
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The cornea accounts for the majority of the refractive power of the eye
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In contrast, the lens is highly elastic, and its
curvature and light bending power can actively change to allow fine focusing- lens
accommodation
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Lens accommodation diminishes with age
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Ciliary muscle contraction loosen the
ciliary zonular fibres and relaxation tightens them
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Consequently
the lens is thin and at a low refractive power
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For close vision, the ciliary
muscles contract, pulling the ciliary body anteriorly toward the pupil and inward, releasing
tension in the ciliary zonule
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Parasympathetic fibres of the oculomotor nerves control contraction of ciliary muscles
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The tear film forms a continuous film across the
eye
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The tear film; provides lubrication, provides
cereal nutrition, removes debris, and provides lysozymes to kill bacteria
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The tear film is an issue for ophthalmic drug release, as
the drug is drained via the tear film, thus the drugs function is not maintained within the
ocular environment
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The neural layer of the
retina is composed of three main types of neurons; photoreceptors, bipolar cells, and
ganglion cells
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The retina
also contains horizontal cells and amacrine cells which play a role in visual processing
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The macula lutea has a minute pit at its centre called
the fovea centralis
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The fovea contains cones only
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Ophthalmic biomaterial devices incorporate metal, ceramic, and polymeric materials
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Advances in microelectronics and
optoelectronic nanomaterials provide new treatment opportunities
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Alternatively, sugar levels in the tear film increase in diabetic patients, by measuring sugar
level in the tear film, smart contact lenses may aid in the management of diabetes
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Greater understanding of stem cell biology has led to new ophthalmic
treatment options
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The key issues with stem cell use include; stem cells may
become a cell type not appropriate for that environment, stem cells may become a cell type
that does not have required function, stem cells may lose physiological function over time, or
stem cells may migrate to an unwanted location
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Refractive errors occur when light rays fail to focus appropriately onto the retina via corneal
and lens refraction causing the formation of blurred images
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Hyperopia- farsightedness, cornea is too flat or
the eye is too short
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Presbyopia - age related loss of elastic lens causing loss of near
vision
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Key issues with contact
lenses include; spoliation with protein, lipid, mucin and bacterial infections, this issue can be
solved with the use of biomimetic coatings (biomimicry- mimics the body's own structures);
patients compliance, this issue is solved with the use of hydrogels which improve ocular
comfort, reduce friction, and improve wettability; another issue is maintaining corneal oxygen
permeability, this issue can be solved by the use of silicone hydrogels which allow high
oxygen permeability
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Gas permeable hard contact lenses are made with a mix of silicone
and fluoropolymers to improve oxygen permeability
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Soft contact lenses have good ocular comfort, good surface wettability,
and good oxygen permeability
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Willis
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, 2001
Willis
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, developed a novel phosphorylcholine-coated silicone-based hydrogel extended
wear contact lenses
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Contact angle analysis confirmed that the coating has a desirable effect on wettability
characteristics
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The
phosphorylcholine coating enhanced the protein resistant effect of the silicone hydrogels,
producing a very low protein-fouling surface compared to other commercial lenses
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However, it is unclear if the results from
such in vitro tests will translate to clinical practice
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Glaucoma is due to raised
intraocular fluid pressure
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The principal surgical treatment is
glaucoma filtration surgery
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An
alternative treatment is the insertion of a glaucoma filtration device
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The tube inside the anterior chamber drains fluid to a
plate fixed to the sclera, aqueous humor is then absorbed into lymph and blood vessels
surrounding the eye
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Artificial corneal implants consist of a clear optic and a peripheral skirt to anchor
the implant
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Boston kPro), P(HEMA) hydrogels (eg
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Desirable characteristics of keratoprosthesis include; a clear central optic with a
porous skirt, biocompatible for a limited inflammatory response, enabling the provision of
adequate nutrients to overlying tissue, and a comparable refractive index
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Sandeman, S
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, 2009
This study considered the use of a hydroxyapatite (HA) coated porous carbon matrix as a
synthetic dental laminate substitute in OOKP design
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The materials were characterized by
scanning electron microscopy (SEM) and HA deposition was characterized by elemental
analysis and X-ray diffractometry (XRD)
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Cellular cytokine production was used
to assess inflammatory potential
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01)
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In addition, the matrices themselves adsorbed significant levels of
the cytokine IL-8 (P<0
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The results indicate that HA coated carbon matrices provide a
suitable environment to enhance in-growth of corneal cells without inducing further

inflammation
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HA coating did not stimulate an inflammatory
response, indicating biocompatibility of the HA coating
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, et al
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However, continuing challenges exist
around tissue availability, inflammation, and transplant rejection
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Peptide cytotoxicity, patterns of cell cytokine expression in response to LPS or IL-1beta
stimulation, and peptide suppression of this response were investigated using
immunocytochemistry
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005)
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The peptide supported LESC
growth when adhered to a silicone hydrogel contact lens indicating potential use in improved
LESC grafting through suppression of inflammation
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Cataracts result from the opacification
of the natural crystalline lens; mainly age related
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The intraocular lens replaces the opaque lens
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Complications of IOLs include;
inflammation, bacterial endophthalmitis, posterior capsule opacification (PCO), corneal
endothelial cell loss, and loss of lens accommodation
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During posterior chamber IOL
insertion, phacoemulsification removes the opaque lens, viscoelastic gel is used to protect
ocular structure and corneal endothelial integrity, the folded IOL is inserted into a capsular
bag where the lens unfolds
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, et al
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To prevent PCO over a long time
span, this study modified IOLs with an antiproliferative drug-loaded hydrophilic coating
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The assembly process was
characterised by quartz crystal microbalance with dissipation (QCM-D)
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In vitro cell experiments

were carried out to monitor the effects of multifunctional coatings in cellular adhesion,
proliferation and migration
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the positively
charged CT DNP were successfully prepared by ionic gelation
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Drug release profiles showed
that surface-functionalized IOL had drug sustained release properties
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The in vivo results showed that the IOLs with multifunctional surface
can effectively reduce the posterior hyperplasia and soemmering’s ring formation
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Retinal implants
Disease such as age related macular degeneration and retinitis pigmentosa, result in the
gradual and permanent destruction of retinal cells
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Alsaeedi
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, 2020
Stem cell based therapy in photorece[tpr and retinal pigment epithelium transplantation is
well received, however, the drawbacks of retinal transplantation is the limited clinical
protocols development, insufficient number of transplanted cells for recovery, the selection of
potential stem cell sources that can be differentiated into the target cells
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Dental pulp stem cells (DPSCs) belong to a subset of
mesenchymal stem cells, and are recently being studied due to its high capability of
differentiating into cells of the neuronal lineage
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