Past, Present And Future Of Regenerative Tissue Engineering

This is a small presentation on the history and possible future of regenerative medicine

1. Past, Present And Future Of Regenerative Tissue Engineering By Subhranil Bhattacharjee

2. What is Tissue engineering ? Tissue engineering can be defined as the design and construction in the laboratory of living of functional components that can be used for replacing or regenerating malfunctioning tissues.

3. In 1955, the kidney became the first entire organ to be replaced in a human between identical twins . Several years later it was performed with allogeneic kidney from a non-genetically identical patient into another. This transplant, which overcame the immunologic barrier, marked a new era in medicine and opened the door for use of transplantation as a means of therapy for different organ systems Every year millions suffer from tissue loss or end stage organ failure. Physicians treat organ and tissue loss by transplanting organs from one individual to another performing surgical reconstruction or using mechanical devices such as kidney dialyzers. Although these therapies have saved and improved lives, they remain imperfect solutions. Transplantation is very limited by a critical donor shortage. In the 1960s, researchers began to combine new devices and materials sciences with cell biology, and a new field that is now termed tissue engineering was born.

4. The terms “ tissue engineering ” and “ regenerative medicine ” have become largely interchangeable, as the field hopes to focus on cures instead of treatments for complex, often chronic, diseases . Langer and Vacanti defined tissue engineering as an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function or a whole organ. On the other hand, regenerative medicine has been defined as the process of replacing or regenerating human cells, tissues or organs to restore or establish normal function. Since they have similar objectives, these two fields merged, originating the broad field of tissue engineering and regenerative medicine also known as TERM.

5. The Past Of Tissue Engineering A pediatric orthopedic surgeon at the Children’s Hospital, W. T. Green, M.D., undertook a number of experiments in the early 1970s a number of experiments were conducted by to generate new cartilage using chondrocytes seeded onto spicules of bone and implanted in nude mice . Although unsuccessful it was correctly concluded that with the advent of innovative biocompatible materials it would be possible to generate new tissue by seeding viable cells onto appropriately configured scaffolds. The following years saw testing on humans to generate a tissue-engineered skin substitute using a collagen matrix to support the growth of dermal fibroblasts.

6. The basic components of tissue engineering are cells, scaffolds, and signals. Tissue engineering strategies generally fall into two categories: the use of acellular scaffolds , which depend on the body's natural ability to regenerate for proper orientation and direction of new tissue growth, and the use of scaffolds seeded with cells. Acellular scaffolds are usually prepared by manufacturing artificial scaffolds or by removing cellular components from tissues via mechanical and chemical manipulation to produce acellular, collagen-rich matrices . These matrices tend to slowly degrade on implantation and are generally replaced by the extracellular matrix (ECM) proteins that are secreted by the in-growing cells.

7. Earlier seeding cells onto available naturally occurring scaffolds was done but they having physical and chemical properties that could not be manipulated, resulted in unpredictable outcomes. So, in the 1980s functional tissue equivalents biomaterials utilizing a branching network of synthetic biocompatible/ biodegradable polymers configured as scaffolds seeded with viable cells. This gave scientists control over the cells. In the 1990s due to sufficient data availability it was necessary to organize a society and to establish a journal dedicated to scientific interactions and the communication of high quality scientific presentations and publications so The Tissue Engineering Society (TES), conceived of and founded by Drs. Charles A. and Joseph P. Vacanti in Boston in 1994. TES would evolve and reorganize to become TESi and then TERMIS, the Tissue Engineering and Regenerative Medicine International Society, by 2005 The journal “Tissue Engineering” was founded later that year

8. Tissue engineering came under public awareness with the airing of a BBC broadcast exploring the potential of tissue-engineered cartilage when it broadcast images of the now infamous “ mouse with the human ear ” fondly referred to as auriculosaurus .

9. Present Of Tissue Engineering The BBC report made Tissue Engineering popularity and the advent research on Stem cell also opened new doors . Stem Cell based Engineering- Stem cells can be defined as undifferentiated cells that can proliferate and have the capacity both to self-renew and to differentiate to one or more types of specialized cells . However, there has been some reconsideration of this definition recently in view of the observation of de-differentiation and trans differentiation of certain mature cells. Stem cells can be isolated from embryos blastocytes or from adult tissue, but the range of cell types to which they can differentiate varies . For tissue engineering, stem cells can provide a virtually inexhaustible cell source. But as there are many ethical and religious concerns associated with ES cells because embryos are destroyed in order to obtain them. so research and use of ESCs were not possible.

10. Other Viable Stem Cell Sources A researcher Yamanaka found a different way of getting stem cells. It is done by transformation of adult somatic cells into pluripotent stem cells through genetic reprogramming in a technique that involves de-differentiation of adult somatic cells (such as fibroblasts) to produce patient-specific pluripotent stem cells. The cells were called iPSC or Induced Pluripotent Stem Cells An alternate source of stem cells was also discovered in amniotic fluid and placenta . Amniotic fluid and the placenta are known to contain multiple partially differentiated cell types derived from the developing fetus. Another alternative was to collect adult stem cells from patient . Adult stem cells, especially hematopoietic stem cells, are the best understood cell type in stem cell biology. Their potential for therapy may be applicable to a myriad of degenerative disorders.

11. Other Techniques Cellular Therapies is another example of tissue engineering. The simplest regenerative medicine strategies are those that are based on the actions of cells, which can be implanted either alone or within a type of carrier material, such as a hydrogel. These cell therapies are designed to inject or implant healthy cells to replace populations of cells that are no longer functioning properly owing to disease or injury . The cells used in these therapies can be autologous cells derived from a tissue biopsy and expanded in culture. Tissue Therapies- Tissue engineering strategies are often referred to as “ growing organs in the laboratory. ” In these strategies, differentiated cells or stem cells are seeded onto a biomaterial scaffold and this construct is allowed to mature in vitro.

12. Future Of Tissue Engineering The major medical challenges of the 21st century are likely to be of a very different variety from those of today. Whereas fighting infectious disease has long been a preoccupation of medicine, in the future, dealing with the consequences of a predominantly aging population is likely to take priority. In spite of significant scientific progress in tissue engineering, there are few examples of human application . Two potential explanations for this may be 1) problems associated with “scale up” or making therapies more common 2) cell death associated with implantation.

13. ECM, in addition to contributing to mechanical integrity, has important signaling and regulatory functions in the development, maintenance, and regeneration of tissues . New innovation in this will help in better cell reprogramming . An important future area of tissue engineering will be to develop improved scaffolds that more nearly recapitulate the biological properties of authentic ECM. Electrospinning has enabled the production of a new generation of highly biocompatible micro- and nano-fibrous scaffolds from materials such as poly(epsilon-caprolactone), from diverse matrix proteins such as collagen, elastin, fibrinogen, and silk fibroin, from polysaccharides, and from carbon nanofibers

14. Bioprinting- Modification of printers to add a z-axis allows the generation of three-dimensional structures. Thus, ’bioprinting’ of cells together with matrix biomaterials and bioactive factors should enable the production of constructs that mimic the architectural complexity, signaling capacity, and cellular distribution of complex tissues. Bioprinting technology for tissue engineering has developed rapidly, and will continue to do so. In closing, finding the most effective ways of using stem cells, from adult, fetal, and embryonic sources, and triggering their differentiation in a controlled manner will provide cell banks for the in vitro growth of tissue and for cell replacement therapy. Developing these concepts from bench to bedside will be crucial in meeting healthcare needs in the new century. The future of tissue engineering is filled with promise and potential. This constantly evolving market is estimated to grow to $17 billion by 2023, a huge increase from $7 billion in 2016.

15. Conclusion Recent advances in different areas such as materials engineering, scaffold processing, gene therapy, and stem cell and applied biology have allowed TERM to be placed on the forefront of new therapies for tissue/organ repair and regeneration. The future is very bright for Tissue engineering and the main hurdles it has to cross are 1). Ethical issues surrounding stem cells and 2). Making the procedure low cost so that more people can afford.

16. Thank You