Tissue Engineering in Otolaryngology: Resident Essentials

What is tissue engineering?

Tissue engineering is the development of biological substitutes for the repair and regeneration of damaged tissues.

• Artificial tissues are prepared in the lab to repair biological tissues that have been damaged or lost as a result of surgery or trauma.
• By replacing that biological tissue with a tissue that has been engineered in a lab, that entire process and procedure, or the entire batch, is called tissue engineering.

The regenerated tissues, especially in the head and neck, are most concerned with bone. However, there could also be a need for the replacement of biological tissues with cartilage and adipose tissue. If there is a need for cartilage, it can be taken from the conchae, septum, and eye crest. There are a lot of areas in our body from which cartilage can be taken, which comes with donor site morbidity. The cartilage may not exactly fit on the same counter. Especially if there is a need to do a nasal reconstruction, patients want a perfect fit of cartilage. It might not be possible to shave and get the cartilage into the right fit because we are not getting the cartilage from the site or near the deficient site. With tissue engineering, we can make or create cartilage that perfectly fits or suits the defective area. So, areas where there is a definite demand are bones and sometimes cartilage. For example, for laryngotracheal reconstruction, we need draft materials.

Tissue engineering for otological surgeries like myringoplasty and tympanoplasty for repair of tympanic membrane perforations that the graft can take up well.

Nowadays, surgeries are manageable even without tissue engineering for all these problems, like otological surgeries or rhinoplasty surgeries. But when a bone is defective, it is always a challenge for the head and neck surgeon.

What is Bone Tissue Engineering?                              

Bone is a complex tissue with a highly porous central spongy bone surrounded by an outer cortical bone. The central bone is spongy, whereas the peripheral bone is a hard cortical bone. If there is a need to mimic a tissue-engineered bone, it should have a similar characteristic that includes a central spongy area and a peripheral, hard cortical area.

Therefore, bone tissue engineering requires the design of a three-dimensional scaffold that closely mimics this anatomical organization of bone. Whenever we do tissue engineering on a bone, we must be able to replicate exactly how the anatomy is present in the normal tissue. Changes in the scaffold geometry can impact the flow media across the scaffold and thus affect the supply of gases, nutrients, and the removal of metabolites.

If this scaffold geometry is not perfect, then the impact of the flow of media that are responsible for growing over the scaffold will be impacted because there will be deficient oxygenation, there will be difficult removal of metabolites, and there will be difficulty in sending the nutrients across the entire tissue evenly. An increase in the pore number and size in various scaffolds is associated with increased vascularization and osseointegration, meaning there will be quite a bit of osseointegration that will be seen even before the time it has to get integrated.

An increase in pore volume will affect the mechanical stability of the scaffold. A good blood supply is required to achieve successful tissue regeneration in the scaffold and the material that will eventually form the bone. If it does not have a good blood supply, eventually, its success will be much less. The best-known angiogenic factor is vascular endothelial growth factor (VEGF), which creates an environment that promotes endothelial cell migration and proliferation. This vascular endothelial growth factor will promote and also create an environment that promotes angiogenesis.

Clinical Trials              

There are critical trials for tissue engineering, and some of them have been successful. Fibroblast growth factor (FGF) has been successfully applied for the repair of tympanic membrane perforations as well as the treatment of aging vocal folds. There is a recombinant human bone morphogenetic protein 7 (rhBMP-7) in a type 1 collagen carrier used for the reconstruction of unilateral and bilateral alveolar cleft defects. There is an angular cleft defect, modulating or getting that bone into an appropriate anatomical plane or anatomical immune structure becomes quite difficult. The recombinant human bone morphogenetic protein 7 (rhBMP-7) in a type 1 collagen carrier is used for angular cleft defects. Tissue engineering can be used for nasal replacement.

Tissue-engineered cartilaginous constructs can provide a good design to fit the specific geometric and functional requirements of a given defect while also avoiding donor site morbidity. Functional breathing and shape will not be compromised. When doing a tissue-engineered product, that cartilaginous product will be able to fit the specific geometrical area that it has to have that is deficient, and you want to reconstruct it so that it does not compromise functional aspects as well.

This will also reduce donor site morbidity through the autogenous removal of cartilage and reconstruction. It can be done with a cartilaginous graph that has been tissue-engineered, or you can take an autogenous graft from the patient. However, autogenous grafts come from donor site morbidity. You cannot contain an extensive amount of graft; there is a limit to it, and replicating the size, shape, and area that you want to reconstruct may not always be possible.

However, this tissue-engineered product cannot come with all the advantages, and it is quite difficult to replicate the size, shape, and mechanical properties of the nasal cartilage. Trials are performed to improvise over time.

Future Research        

Molecular therapy in bone bioengineering

In bone bioengineering, modification of the properties of cells at the molecular level can have a significant impact on the remodeling or production of bioengineered bone. Liposome-mediated and adenovirus-mediated BMP-2 (bone morphogenic protein) gene transfer into mesenchymal cells (MSCs) in preclinical studies. It has resulted in cells that can repair critical-size bone defects.

• A liposome mediator and adenovirus mediator or vehicles are used to transfer the bone, which is called coding for the BMP-2 gene, into the mesenchymal cells.
• Once the BMP gene gets into the mesenchymal cells and the bone morphogenic protein gets coded from there onwards, you will have good bone formation, which will eventually repair the defective gene.

Gene-modified cells could potentially be given all the properties required for tissue regeneration, and they could then be implanted into the surgical defect.

• To close the surgical defect, these gene-modified cells have all the properties that are required for regeneration, and they would expect regeneration. Once the tissue has regenerated, it can be implanted into the surgical site.

Alternatively, these cells could be placed in a bioreactor to create the required tissue "bone,” and then they would be implanted into the surgical recipient site. You can put it at the site of the defect directly, or you can put it in a bioreactor and wait for the tissue to grow. Once it has grown in the external environment, you can put it at the surgical site.

Biomimetic Scaffolds                                                        

With the help of computer-based solid-free-form fabrication (SFF) using 3D printers, it is possible to make a custom-made scaffold designed specifically to fit the defect that is being treated. You can do a three-dimensional analysis printed in 3D of the exact defect that will be treated, and the computer-based solid freeform fabrication will help us to develop the correct scaffold. Over the scaffold, you can have the tissue grow. Also, nano-topography and nano-chemistry on scaffolds can be structured in detail to try and reproduce natural tissue that is designed to be replaced, even at the cellular level. Nanotopography can identify topologically the area defects, which include

• What is it made of?
• What is the genetic constitution?
• Then, develop natural tissue.

Improved Vascularity

Improvement of vascularity is important because any tissue when it is being developed, thrives on its vascularity. Newer methods to increase vascularity at the donor site will significantly enhance the regenerative abilities. The bioreactors mentioned earlier can help in this respect, but specific methods of inducing controlled vascular proliferation within the surgical site still need to be developed using synthetic polymers. With the help of synthetic polymers, we should try to incorporate controlled vascular proliferation within the surgical site.

Hope you found this blog helpful for your Basic Sciences Preparation. For more informative and interesting posts like these, keep reading PrepLadder’s blogs. 

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