In the realm of modern medicine, novel therapies based on regenerative medicine and tissue engineering have been evolving as a revolutionary area with the promise to transform healthcare. Tissue engineering, a pioneering field that combines biology, medicine, and engineering, aims to solve some of humanity’s most critical medical issues by designing functional artificial organs, tissues, and organoids. From replacing damaged organs and advancing drug testing to enabling personalized medicine, this multidisciplinary science is redefining the future of medicine. Let’s embark on the amazing journey where creativity meets technology, unraveling the mysteries of human biology and turning formally impossible dreams into reality!

What is Tissue Engineering?

Tissue engineering is the application of technical, medical, and physiological methods and concepts to develop new tissues with similar properties and functions as a biological replacement for implantation into the body to replace, repair, or enhance organ functions.

Tissue engineering utilizes scaffold matrices to fill the tissue spaces, provide structural support, and release growth factors that can form tissues in the body. Regenerative medicine and tissue engineering methods involve integrating and interacting with cells and tissues by incorporating suitable physical, mechanical, and biochemical cues. Therefore, the inclusion of modifying components such as DNA and physiologically active proteins is essential to the success of the process.

Applications of Tissue Engineering?

Tissue engineering has enormous and revolutionary applications from artificial organs to brain-in-a-dish models!

• Artificial Organs: Stem or differentiated cells are seeded into the biomaterial scaffolds developed in a bioreactor and transplanted to substitute defective organs, as proven by the successful development of hollow organs such as bladders, urethra, and blood vessels.
• Tissue Repair: Advanced therapies using bioengineered skin substitutes and mesenchymal stem cells offer solutions for chronic wounds and burn injuries, overcoming the limitations of traditional grafts like autografts, and allografts which often face rejection risks.
• Organoids: They are self-organizing 3D masses of cells, stem cell derived, replicate tissue morphology, and are precious for the study of development, disease, and drug response.
• Drug Testing and Disease Modeling: Tissue-engineered structures and organoids enable human relevant platforms to test new drugs.

This minimizes dependency on animal models and increases accuracy of preclinical studies

Stem Cells – The Heart of Tissue Engineering

Stem cells form the basis of tissue engineering and play a critical role in the formation of working tissues and organs due to their remarkable ability to self-renew and differentiate into various cell types. They can be induced to become tissue- or organ-specific cells with special functions under some physiologic or experimental conditions. For instance, stem cells in certain organs, e.g., the gut and bone marrow, divide regularly to renew and replace exhausted or damaged tissues. In other organs, including the pancreas and heart, stem cells divide only under special conditions.

There are three major categories of stem cells employed in tissue engineering:

• Embryonic Stem Cells (ESCs): Derived from pre-implantation, these are pluripotent and can differentiate into any cell type.
• Adult Stem Cells: Derived from adult organs, these are multipotent stem cells that can differentiate only to a restricted array of cells.
• iPSC’s: These are reprogrammed adult stem cells that retain their pluripotency

By supplying the specialized cells needed to rebuild damaged tissue, e.g., cardiomyocytes for repair of the heart, chondrocytes for regenerating cartilage, or neurons for repairing the nervous system, these cells play a critical role in tissue engineering.

Breakthroughs and Success Stories

In 2006, the first bladders made in a lab were successfully put into human patients. The cells of the patient were seeded onto biodegradable scaffolds to create such bladders, allowing the tissue to develop and mature in the laboratory prior to transplantation. Treating heart failure by transferring a 3D bio-printed cardiac patch that is customized to the individual patient into the infarcted region of the myocardium has been explored as a future treatment. Brain organoids have been successfully developed to investigate neurological diseases such as Alzheimer's, Parkinson's disease, etc. Bone and cartilage repair have come a long way due to tissue engineering. For example, the FDA-cleared procedure called MACI (Matrix-Induced Autologous Chondrocyte Implantation) fixes injured knee tissue through the patient's cartilage cells. Likewise, in place of traditional bone transplants, engineered bone grafts are being used to fix fractures and bone defects. Mesenchymal stem cells (MSCs) have been employed to regenerate injured heart tissue and fix spinal cord damage. In fact, human umbilical cord mesenchymal stem cells (hUC-MSCs) were employed in the treatment of a critical COVID-19 Patient with severe pneumonia and acute respiratory distress syndrome (ARDS). The therapeutic potential of hUC-MSCs as an efficient and safe treatment option for critical COVID-19 was established through the rapid improvement of lung function, reduced inflammation, and smooth recovery after hUC-MSC transplantation

Challenges in Tissue Engineering:

In spite of its vast potential, tissue engineering is fraught with several challenges including vascularization. Development of a viable network of blood vessels is essential for the delivery of oxygen and nutrients for cellular growth. The whole process of tissue engineering at a large scale is time-consuming and expensive. Ordinary individuals are unable to afford stem cell therapies/tissue therapies as they are highly expensive.

The application of stem cells, and animal testing is ethically problematic because of which regulatory approvals are time-consuming and difficult. The success of implants is not a guarantee for long-term stability given the degradation of scaffolds, or loss of cell function. While tissue engineering circumvents immune rejection, making the engineered tissues/organs biocompatible is still a significant challenge.

Future Prospects in Tissue Engineering

Tissue engineering is growing at a never-before-seen rate because of new technologies and innovative thinking. In the future, completely functional, lab-cultured organs will solve the world's organ shortage and end the demand for donor transplants. New technologies such as 3D bioprinting, CRISPR gene editing, and intelligent biomaterials will enable the precise generation of intricate, patient-matched tissues, and the integration of artificial intelligence (AI) and machine learning will streamline tissue design and predict outcomes, accelerating development. Tissue engineering may revolutionize space exploration (e.g., cultivating tissues to address challenges or tissue/muscle loss in astronauts) and sustainable food production (e.g. Lab-grown meat). As research continues, tissue engineering may lengthen lifespans, enhance well-being, and reshape industries globally.

References:

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Authors:

Ms. Sadhana Ravindran (M. Tech. Int. Biotechnology, Second-Year Student) and Dr. Ashwini Puntambekar (Assistant Professor)

Protein Biochemistry Research Center,

Dr. D. Y. Patil Biotechnology and Bioinformatics Institute,

Dr. D. Y. Patil Vidyapeeth, Pune - 411033, Maharashtra, India.

Email: ashwini.puntambekar@dpu.edu.in