The Future of Tissue Engineering: Peptide-based Biomaterials
The medical and research fields have experienced significant technological growth. Most biological processes are becoming simpler each day due to advanced technology. Additionally, more inventions and discoveries are being made. Scientists can now efficiently study organs, cells, and tissues, as well as their roles in the body.
For example, the improved recombinant antibody production process has facilitated large-scale production, which is used in manufacturing medicines and vaccines.
Major biotech fields, such as protein production, have also experienced a paradigm shift. Scientists can now obtain specific proteins through protein production and protein expression services for research and medicinal purposes.
Moreover, tissue engineering has made tremendous and promising strides over the last few years. The field is still evolving rapidly, and the future seems bright. With current developments, it’s possible to control cells and their surroundings more easily. Additionally, tissue engineering allows for the synthesis of living organs and tissues for clinical use.
Some technologies and trends that led to these significant impacts in tissue engineering include new stem-cell sources, smart biomaterials, vascular engineering, advanced 3D bioprinting, microfluidic-based physiological platforms, and bioreactors.
However, the field also faces significant challenges, such as reducing the immunogenicity of engineered tissues and navigating regulatory hurdles, among others. The following article will focus on tissue engineering, looking at the future of this promising field.
What is Tissue Engineering?
Let's start by defining what tissue engineering is. This biomedical engineering field applies the combination of cells, ideal biochemical and physicochemical factors, material techniques, and engineering to restore, improve, replace, or maintain various types of biological tissues.
Tissue engineering primarily involves the application of cells onto tissue scaffolds to form new, viable tissues, which are used in medicine and for other purposes. For some time, tissue engineering was classified as a sub-field of biomaterials. However, due to significant improvements and growth in its scope and applications, it is now considered a field on its own.
But how does tissue engineering work? Defining and knowing the scope and application of tissue engineering is insufficient to provide a clear picture of the entire field. The most important thing is to understand how it works.
According to the definition, tissue engineering has various applications, including repairing or replacing tissues like bone, blood vessels, the bladder, cartilage, and muscles. To ensure proper functioning, these tissues require specific structural and mechanical properties. Tissue engineering also works with the immune system to fight against bacteria, viruses, and other disease-causing organisms.
This is why antibody production, a significant component of the immune system, is essential in tissue engineering. Scientists who want to study the properties, functions, and roles of antibodies in tissue engineering use custom antibodies.
Tissue Engineering Versus Conventional Grafting
Tissue engineering is an ideal alternative technique to conventional grafting. By definition, grafts are surgical procedures tailored to move tissues from one location to another or from one patient/donor to another. The process is meant to replace damaged bone, skin, nerves, cartilage, or cells with functional and healthy ones.
On the other hand, biomaterials used in tissue engineering include cells, scaffolds, and bioactive molecules. Combining these synergistically proves to be a safer and more ideal tissue regeneration and repair method.
Interest in tissue engineering has significantly increased due to the prevalence of many chronic diseases, the unavailability of donors for conventional grafting, and the challenges or limitations of medical transplants. The primary aim of tissue engineering biomaterials is to enhance tissue regeneration in patients through cell-free supports modified with bioactive molecules or a combination of these modified scaffolds.
Cells and Scaffolds Used in Biomaterials for Tissue Engineering
Scaffolds are developed to mimic the natural extracellular matrix (ECM). They are biodegradable, biocompatible, stable, and porous structures that help to support cellular growth. Natural polymers used in these structures include elastin, collagen, hyaluronic acid, and chitosan.
Additionally, several synthetic polymers are used in scaffolds for tissue engineering, such as polylactic acid (PLA), polyglycolic acid (PGA), and poly-ε-caprolactone (PCL).
Both synthetic and natural polymers have their advantages and disadvantages. For example, natural polymers have higher biocompatibility but are known to have poor mechanical properties, which can lead to premature breakdown.
On the other hand, synthetic polymers are more stable compared to natural polymers but often have low biocompatibility, potentially leading to increased inflammation and the possible rejection of the biomaterial. Boosting these polymers' biocompatibility helps reduce the risk of adverse reactions. This is achieved through the modification of the scaffold surface with bioactive molecules.
Cells are also essential components of biomaterials in tissue engineering. Adult mesenchymal stem cells (MSCs), isolated from bone marrow or adipose tissue, are used as the gold standard for tissue engineering and regenerative medicine. They can self-renew and differentiate into various cell types, making them vital to the development of new and healthy tissues.
What are the bioactive molecules used in biomaterials for tissue engineering?
Peptides play a significant role as catalysts for polymeric scaffolds among all the biomolecules applied in biomaterials for tissue engineering. Peptide-modified scaffolds portray similar features to protein-modified biomaterials. However, unlike proteins, using peptide-based biomaterials in tissue engineering offers tremendous advantages.
For example, peptide synthesis is more affordable and uses a more straightforward process than protein expression; additionally, peptide modification is simple, has lower immunogenicity than large protein particles, and consists of small molecules that are resistant to environmental changes such as pH and temperature.
Due to such advantages, peptides are the ideal bioactive component of biomaterials used in tissue engineering applications. Peptides have different classes that are used as biomaterials for tissue engineering.
These classes are meant to enhance the biocompatibility of biomaterials. For instance, cell adhesion peptides improve cell adhesion, differentiation, and proliferation. On the other hand, BMP-like and VEGF-like peptides help to mimic proteins by managing bone repair and controlling blood vessel growth.
Moreover, self-assembled peptides (SAPs) possess a specific structural section. They form a complex 3D structure that helps them to assemble spontaneously through non-covalent bonds, such as hydrophobic interactions, hydrogen bonds, and electrostatic interactions. This process can be induced by external factors such as chemical molecules, temperature, or pH.
Similarly, other classes of peptides, such as SAPs, can be synthesized through solid-phase custom peptide synthesis. Furthermore, complex nanostructures can be developed under physiological conditions, making the process efficient and affordable. Peptide hydrogel structures can also mimic the extracellular matrix and play the role of scaffolds for tissue-regenerating biomaterials.
What are the applications of tissue engineering?
1. Regeneration of Damaged Tissues
Tissue engineering has been used to overcome the problems associated with damaged tissues. The regeneration of damaged tissues is applied in the following ways:
- Bone Tissue Engineering
Bones comprise collagen and minerals, which can regenerate and repair in response to injuries. Bone grafting is required when there are large bone defects due to infection, trauma, resection, or skeletal abnormalities. Therefore, bone tissue engineering proves effective in the regeneration of damaged tissues.
However, it's challenging to reproduce the features of bones in vitro. This makes obtaining a perfect scaffold for bone tissue regeneration difficult. Nevertheless, scientists have developed 3D porous scaffolds with similar characteristics to natural bone, utilizing bioceramic scaffolds for excellent compatibility.
Additionally, osteoinductive scaffolds apply biomolecular signaling and progenitor cells to form new bone tissue.
- Cartilage Tissue Engineering
Cartilage is a connective tissue found in joints such as knees, elbows, and ankles. Like bone engineering, cartilage tissue engineering also faces many challenges. Though many scaffolds have been applied in cartilage repair, synthetic options such as polyethylene glycol (PEG), polyurethane, and elastin-based polymers are the most commonly used.
Cartilage is primarily made up of chondrocytes. Therefore, autologous chondrocytes are ideal cell sources for cartilage regeneration and repair. However, these autologous chondrocytes are hard to obtain and may require advanced harvesting techniques.
Therefore, Mesenchymal Stem Cells (MSCs) generated from various sources, such as bone marrow or adipose tissue, are ideal alternatives. They can differentiate and proliferate into adipogenic, osteogenic, myogenic, and chondrogenic lineages and can be integrated in vitro.
Besides cartilage and bone tissue engineering, other forms of tissue engineering for damaged tissue regeneration exist, for example, cardiac, vascular, and pancreatic tissue engineering.
2. In-Vitro Human Models for Tissue Engineering
Developing in vitro human models for tissue engineering is a significant application used to examine the roles played by various mechanical, physical, and chemical factors in biological systems. Some of these applications include:
- Cancer
Precise modeling of the tumor microenvironment is needed to better understand the tumor progression process. This is achieved through 3D cultures, which offer microenvironmental conditions that help replicate tumorigenesis. A 3D culture is based on integrating biomolecules, cells, and scaffolds. Both synthetic and natural biomaterials are used in modeling cancer.
- Drug Discovery
3D cultures have been introduced to drug screening to help analyze the impact of drug actions. Moreover, these 3D cultures help hepatocytes regain their key liver protein expression and morphology.
3. Regenerative Medicines Repair of Damaged Tissues and Organs
Regenerative medicine involves helping the body induce its own repair mechanisms to treat damaged organs or tissues. When the body cannot naturally develop this mechanism, the organs or tissues can be engineered in the laboratory and implanted. Additionally, regenerative medicine uses stem cells and tissue engineering through a process known as directed differentiation.
The directed differentiation process begins with developing scaffolds and then introducing cells. The tissue then develops within an ideal environment. In other cases, self-assembly may involve mixing scaffolds, growth factors, and cells.
Another technique applied in regenerative medicine is the stripping of cells from a donor organ and using the remaining collagen scaffold to develop new and functional tissues. This method has been effective for liver, heart, kidney, and lung tissue.
What is the future of tissue engineering and regenerative medicine?
With advanced technology, the future of tissue engineering is promising. Just as previous innovations have established tissue engineering as a field in its own right, new technologies will continue to drive its progress and expansion.
One of these new technologies involves expanding and isolating stem cells while detecting the signals needed for their differentiation. Other emerging technologies include the genetic modification of cells in vivo and in vitro, and neural tissue engineering. These technologies will help solve the challenges experienced when harvesting adequate autologous cells to create viable tissues.
Moreover, new matrix materials with specific chemical structures and compositions will be developed to ensure they serve effectively as insoluble regulators. Additionally, introducing new methods to help control the mechanical environment in vitro will help regulate biosynthetic behavior.
All these techniques will facilitate the synthesis of tissues in vitro that closely mimic native materials. They are also significant in the preparation of implants that allow tissue regeneration in vivo.
Further, cell proliferation in monolayer cultures and growth in 3D scaffolds for tissue engineering will likely improve, providing many opportunities to assess specific cell behavior. This means the knowledge of cell phenotypes will be enhanced, leading to tremendous advancement in regenerative medicine and tissue engineering.
Another research area is the development of human liver models in mice. The main aim is to observe the interaction of drugs in animal models compared to the human system. Such studies are facilitated by tissue engineering. Moreover, the regeneration of new organs, such as the kidney, is still under investigation.
This will provide a significant boost to the tissue engineering field. The ability to regenerate new functional kidneys would be a breakthrough, as it would help overcome organ transplant challenges, such as donor shortages.
Wrapping Up
Tissue engineering significantly impacts tissue and organ repair and other lifesaving processes. It helps to overcome the many shortcomings associated with transplants and allografts. However, tissue engineering is often expensive and requires high-level skills, experience, and thorough research.
Nevertheless, technology has simplified these processes and positioned tissue engineering as an outstanding field. Further advancements and research are ongoing to improve the discipline and make it even more effective.
Progress in areas such as cartilage, bone, vasculature, heart, and pancreas engineering has shifted tissue engineering to higher levels. This has led to the transformation of the biotechnology field by bringing forth new processes and therapies. For example, the generation of custom antibodies, protein production, custom peptide synthesis, and gene synthesis have all been significantly enhanced and streamlined.