Hypothetical Design and In Vitro Testing of a Directly Implantable Biodegradable Scaffold for Cartilage and Osteochondral Defects

This document discusses the hypothetical design and in vitro testing of a directly implantable biodegradable scaffold for cartilage and osteochondral defects. It explores the clinical need for such a scaffold, the properties of the scaffold, surface treatment regimes, and preliminary in vitro tests.

Hypothetical design and in vitro testing of a directly implantable biodegradable scaffold
for cartilage and osteochondral defects
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Hypothetical design and in vitro testing of the directly implantable biodegradable scaffold for
cartilage and defects of osteochondral.
Section 1: Describe the clinical need
The term orthopaedic surgery refers to the various changes in the defects associated to the
articular cartilage. However, the poor capacity of healing is related to a vascular that is the
key aspect of motivation of research. The technique, which is used, does not imitate the
properties of biochemical and biological cartilage articulate. The approaches of medical have
emphasized the engineering of rigid scaffolds that do not allow for the seeding and
penetration in the process. The use of rigid scaffold, cell therapies and hydrogels are used on
extensive basis to overcome issues in consideration to cartilage repair and healing (Khatab et
al., 2018).
Native articular cartilage repair and healing management provides a compartmental structure,
which requires adequate development in imitating the structure. Articular cartilage entails the
resolution of the joint loads to various levels of the sub-chondral bone, which leads to an
impact, making the smooth flow of the friction. It further helps in the process of glidal
movement. The cartilage degeneration occurs after the trauma when the recovery process
gets slow, and non-existent and the cartilage of the articular often lacks the required healing
power to facilitate the process.
The articular cartilage connective influence on the tissue of extracellular matrices, the
collagens, proteoglycans, and water. The matrix contains the dry weight and reduced quantity
of collagen types V, CI, IX, X, XI, that is interconnected to the proteoglycans and
hyaluronate that considers the estimate of 10% weight of the total (Jiao et al.,2016).
Degradation and lesion are the major defects occurring in the articular cartilage, and various
surgical methods have been used for managing this. It consists of the micro fracturing and
mesenchymal stem cell implants, and using this many of the issues have been identified in
this case. The issues include the survival rate, and the cartilage regeneration acts as major
challenge because of the chondrocytes and maturity of human lymphatic system. In addition,

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the presence of the vasculature posing reduced proliferation and the ability of migration
(McAlindon et al., 2017).
Lesion development often generate osteochondral development, therefore it states the need to
reconstruct the cartilage and management of the sub-chondral bone that have different
physiological functions. It poses some issues for the aspect of developing a single scaffold
that addresses both i.e. cartilage’s double restructuring and the sub-chondral bone, without
any defects (Piaia, Salmoria and Hotza, 2018).
The earlier kind of the antilogous osteochondral-mosaicplasty often creates issues and is
derived from the non-weighty parts of the articular cartilage. Moreover, the effects are often
utilised in the management of the damage to the cartilage and subchondral effects. It is not
linked to the significant high cost of management, and the risk of immunologic rejection and
pathogen transmission issues (Ruiz-Heiland et al., 2012).
The tissue of subchondral plays a major function of the osteoarthritis, which relates to the
initiation and termination process. The presence of the bioactive ceramics contributes to the
promotion of the subchondral and cartilage regeneration. Different implants have been
developed, wherever the poor mechanical properties and declined properties of biological
mechanism have hampered the application of scaffolds. However, due to the complex
interface that occurs between the cartilage and subchondral bone, the imitation of the natural
structure and the physiological functions of the issues becomes an issue. Due to this, there
arise needs for developing the intelligence of scaffold, which have bilenage property, which
is able to fit or adjust to the cartilage and subchondral microstructure. The aspects of benefits
to the patients in context to development are geared towards the beneficial effects to the
patients in this development are facilitated. This plays a vital role for maintaining human
tissue function in the bone (Liu et al., 2013).
In the management, the process of Strontium oxide (SrO) and silicon dioxide (SiO2) are
significant and it contributes a major role towards maintaining the human tissue functions in
the bones. It has been analysed through the studies that Sr increases the osteoconductivity
action of the calcium phosphates and other functions of the bone tissue property. In addition,
Sr also fosters the aspect of differentiation of osteoblast and the vital function in the
degeneration of cartilage and reducing the level of apoptosis chondrocyte, as it is required for
the process of osteoarthritis therapy (Yu et al., 2013).

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On the other hand, Si is the main component that is essential in the development of
connective tissue, as in the articulate cartilage and bone development process. It is found in
the process of mineralization process of been formation and promotes the growth of the
skeletal tissues and initiates development. Furthermore, Si stimulates the process of
extracellular matrix promoting the proliferation process and management of the osteoarthritis
(Madry et al., 2017).
The inclusion of both Sr and Si are important to the improvement of the state of
chondrocytes in the cartilage areas. Bio-cyte scaffolds entailing Sr and Di are efficient in the
management of the osteochondral defect and restoration of the cartilage and sub chondrial
bone and, degeneration occurs at osteoarthritis stage
The development of the SPS scaffolds becomes vital in the investigation of the regeneration
of osteochondral. The function of Sr and Si ions have the bioactive ceramic compound on
the role, as it plays the protection of the cartilage from osteoarthritis state and it further
raises the reconstruction successfully (Gong et al., 2019).
Section 2: The scaffold
Development for the Sr and Si are based on the scaffold bioceramics that is synthesized
from the solid state reaction method. The scaffold SPSS will be developed from the 3D
printing devices using the computer-aided designs. The SPS scaffold will be derived from
mixing SPS powders and sodium alginate utilising the specific ratio than the addition of 20
wt% of Poloxamer and mixed till homogeneity. The formed paste will be loaded into the
printing tube, excluded to fabricate the primary scaffold. Later drying will be initiated over
cool temperature for over 3 hours at 1400 degree Celsius, leading to the development of the
SPS scaffold (Hu et al., 2017).
The used silicon dioxide (SiO2) and strontium oxide (SrO) will be derived from Sinophram
Group Limited. The use of Ammonium dihydrogen phosphate and sodium alginate are
obtained from the pharmaceutical company (Yu et al., 2013).
The underlying properties for Si and Sr to preserve the chondrocytes from the osteoarthritis
supported towards the expression of the pathway of hedgehog signalling. The Si and Sr have
the effect of downgrading the controlled mechanism of action on the hedgehog pathway.

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They coordinate positively cooperate positively towards the gene pathway. Si and Sr can
additionally inhibit the related genes in the concentration range of Sr ions and Si ions (Filardo
et al., 2016).
The effect of Si and Sr in the scaffolds is aimed towards the expression of enhancing the
autophagy markers concentration. Further, the consequential expression of the gene
expression with the set concentration levels of Si and Sr. SPS scaffolds ability responds to the
chondrocytes, as it will determine undertaking the in vitro studies. Further, the stimulatory
effects of the SPS scaffolds are also essential on the effects of osteochondral regeneration are
essential (Korovessis et al., 2018 ).
Section 3: Surface treatment regimes
The treatment symptomatic chondral lesions are important points as it entails the use and
utilisation of the non-operative treatments. These treatments entail excision, the exclusion
bone marrow stimulation, and bone grafting, retrograde drilling, transplants and limited
replacement of the prosthetic. The goal of the treatments is facilitated towards reducing the
symptoms and preventions of the development of osteoarthritis for the long period. Despite
this, it has been found that none of the studies has demonstrated the defects of the long term
deterioration of ankle joint (Meckes et al., 2017).
Main key options of the surface treatment for osteochondral are essential for the management
of the pain. Various factors are important as they play a vital role that consist of intra-
articular pressure, elevated levels of intra osteo-pressure, and synovial pain or bone pain.
The other treatment approach that has been used entails the injection of the intra articular, and
this is invasive method essential for the delivery of the compounds into the joint regions. This
is used in the outpatient settings and often used for treating and assessing the efficacy that is
used for the osteoarthritis state of the patient. The corticoid injection has been utilised as the
management of the anti-inflammatory management agent for reducing the pain (Rodrigues et
al., 2018). The beneficial effects involve application for low dosage and associated gross
cartilage damage and the toxicity of chondrocyte, accelerating the growth of the osteoarthritis
(Thompson et al., 2015). Further injection with the platelet-rich plasma has high protease,

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cytokines and other signaling pathways products have been used. The injections of Intra-
articular are also used for reducing the levels of the pain (Gong et al., 2019).
Surgical treatments are also offered for the management of articular cartilage and the
management of osteo chondria. Microfracture techniques used entail the use of abrasion and
drilling methods that often disturbs the subchondral bone and cream channel of defect
cartilage at the end in the bone marrow. This method is beneficial for the small levels of
defects, and also provides relative formation of the fibro cartilage articular cartilage (Yousefi
et al., 2015).
Section 4: Preliminary In vitro test
The SrO and the silica of mesoporous will be also used to obtain the Si and Sr ions, as the
concentration of the Sr and Si will be determined. Total genes of the RNA will be collected
after the task of culturing of the chondrocytes has been done in the ionic solutions. The
expression of the genes of chondrocytes and the genes in HIF pathway was checked. Them
analysing the stimulation effect of SR AND Si ions solutions, treatment of the chondrocytes
was carried out. The stimulatory effect will be performed using the confocal laser-scanning
microscope CSLM, and the acquired images from the laser line 405nm and 568 nm. The
collected and the analyzed images will be measured in terms of quantity within COL II
protein images (Okita et al., 2015).
In assessing the mechanisms for Sr and Si preserved within chondrocytes of the osteoarthritis,
for assessment the investigation of gene metabolic pathway is used. Usage of Indian
hedgehog will be utilised for assessing the pathway, exploring the mechanisms of Sr and Si in
the protected chondrocytes (). To include the Indian Hedgehog Pathway, smoothening of the
antagonist is utilised in the Pathway and fabricate positive control group.
Later on, the DNA will be therefore obtained and RNA genes thus investigated. The
software Oligo 7.0 will be also used for designing the primer sequences for review.

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