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What is the development status and application prospects of regenerative medicine based on tissue engineering?

Thank you

@元林

for the invitation! To fully answer this question would require writing a review, which is obviously not what you want to see. Therefore, the respondent made some general explanations and discussions based on his own understanding.

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First of all, let’s talk about two important concepts: Tissue Engineering and Regenerative Medicine

Tissue Engineering is a multi-disciplinary It fully applies the principles of engineering science, biological science, and basic medicine to develop and manufacture biologically active tissue or organ substitutes to maintain, replace, repair, and even enhance the functions of diseased tissues and organs. This concept was proposed by Robert Langer (MIT) and Joseph Vacanti (Massachusetts General Hospital) in the late 1980s and early 1990s, and published research papers in Science to explain the concept and basic principles.

Regenerative Medicine is a broader definition that includes tissue engineering, but also includes self-healing of the body tissue system. Tissue Engineering ) and regenerative medicine are currently widely used interchangeably, mainly because the ultimate goal of tissue engineering is to replace or enhance the self-repair of tissues to cure complex chronic diseases.

（Tissue engineered human ear, credit: Harvard University）

After more than 20 years of development, tissue engineering has made great achievements in basic research, clinical application, and market transformation. A very significant development, and its research results have changed clinical treatment ideas to a great extent and benefited a large number of patients. Although it is a relatively new subject, it has attracted a lot of attention since its birth. Countries (the United States, Japan, Singapore, China, etc.) are investing high amounts of research funds to promote the development of this subject. At the same time, a large number of related researchers (clinicians, engineers, biologists, chemists, Material scientists, etc.) are attracted to this potential field and use their more professional knowledge and skills in their respective fields to continuously promote the development of the tissue engineering discipline.

It is worth pointing out that China has invested unprecedented human and financial resources in the field of tissue engineering in recent years. In the ten years from 1999 to 2009, the Chinese government invested more than 500 million RMB in the research and development of tissue engineering. clinical application. Science magazine published a review "China's Push in Tissue Engineering" in 2012, reporting on China's development in this area, and also reported on China's pioneers in this field: Gu Xiaosong from Nantong University (Nervous System), Cao Yilin from Shanghai Jiao Tong University ( Skeletal system), Cui Fuzhai (Brain tissue) of Tsinghua University.

For regenerative medicine, tissue engineering is currently making continuous developments and breakthroughs in the following directions:

1. Cell source

Regeneration of target tissue or Organs usually require the use of corresponding cells, such as cardiomyocytes (heart), epithelial cells (skin), skeletal muscle cells (muscles), etc. However, many cells are separated from their own native environment and cannot maintain their function and activity for a long time in vitro. For example, the in vitro culture of liver cells has always been a problem. Therefore, the acquisition of new cell sources is extremely important. The use of pluripotent stem cells can solve this problem to a great extent. Embryonic Stem Cells and Induced Pluripotent Stem Cells (iPS cells) are currently the focus of research. Especially iPS cells, because of their unique functions and the fact that they do not cause ethical issues, have become the darling of researchers around the world. Develop its new applications for directed differentiation of specific tissues and organs.

At the same time, tissue stem cells are more specific than pluripotent stem cells, such as bone marrow stromal cells, adipose-derived stem cells, umbilical cord blood stem cells, etc. etc., have also been used by researchers for the regeneration of different tissues. More specific cells such as chondrogenic progenitor cells and cardiac progenitor cells have also been successfully isolated and used for the regeneration of corresponding tissues.

(iPS cells forming a colony, credit: Flickr)

2. New biomaterials

Successful tissue engineering must be inseparable from the discipline of biomaterials develop. To regenerate biological tissues with different properties, material selection is crucial. In the early days of tissue engineering, materials were often used as scaffolds to support cell attachment and growth. At present, the development of new materials mainly focuses on the biological properties of materials. New materials must not only serve as scaffolds, but also interact with cells to induce cell migration, expansion, and directional differentiation. At the same time, new materials are also endowed with the function of regulating the microenvironment of cell growth, such as releasing growth factors, transmitting signaling factors, inhibiting inflammation, etc. New biomaterials that are more capable of self-assembly can self-assemble into the form of target tissues or organs at a specific time and in a specific microenvironment under external stimulation. Although these studies are still in the early stages of exploration, exciting breakthroughs can be expected in the future.

(Biomimetic liver tissue engineered from novel biomaterials, credit: NIH)

3. Signaling factors

For in vitro cell culture, there is a lack of native factors in the body Environmental and related signaling factors make it difficult to successfully and efficiently differentiate into target tissues and organs. After years of research, the growth factors required for directional differentiation of some tissues have been gradually identified. Traditional tissue engineering methods usually directly apply a defined combination of growth factors to cultured cells or cell-loaded scaffold materials. However, the isolation and purification of growth factors is time-consuming, labor-intensive and expensive, so it is not the best choice for long-term use. Current developments in this field mainly focus on chemical small molecules, genes, physical stimulation, etc. Through the action of small chemical molecules, biological signaling pathways equivalent to those of growth factors can be activated, thus inducing cell differentiation. Gene transduction enables the cells themselves to differentiate and acquire functions without the need for external stimulation. Physical stimulation during the differentiation process of different target tissues, such as weightlessness, pressure, surface structure of scaffold materials, etc., can also promote cell differentiation. Combining new biomaterials and merging different signaling factors and materials is also a research hotspot, the so-called "Smart Material". For example, scaffolds with sustained drug release function, hydrosols loaded with plasmid DNA, etc.

(Recellularization of decellularized rat kidney, credit: Harvard Medical School)

4. Biofabrication method

Biofabrication is a relatively new As the name suggests, it is to use the basic elements that constitute organisms (cells, growth factors, biological materials, etc.) to create functional biological tissues or organs, or biological systems for research. Here we will mainly talk about the former. The most traditional tissue engineering manufacturing method is to load cells into 3D scaffolds and culture them in an environment with growth factors. After years of development, a large number of manufacturing methods for different tissues have been developed. For example, recellularization of decellularized organs (Decellularization) has been used in experiments for tissue engineering of liver, kidney, heart, etc.; 3D assembly of cell sheet (Cell sheet) has also been successfully applied to cartilage. , blood vessels, skin and other tissues, and clinical products have been used on patients; micro-tissue (micro-tissue), as the basic structural unit, has also been successfully used for the regeneration of blood vessels, liver tissue, muscle tissue, etc. The emergence of the currently very popular 3D bioprinting technology has brought another new revolution to tissue engineering and regenerative medicine. Due to its precise control capabilities and personalized features, it is possible to customize human tissues and organs. Although 3D bioprinting is in the early stages of research and there are many difficulties to overcome (please see:

What are the main difficulties of 3D bioprinting

), as the technology matures and organizations With the development of engineering, it is not a fantasy to successfully 3D bioprint human organs.

(3D bioprinting for tissue engineering, credit: Wake Forest University)

Tissue Engineering (Tissue Engineering) has been continuously developing and progressing, although a large number of research results are still limited to the laboratory stage, but many technologies have already entered clinical transformation and even marketization. Not only its application in the medical field, the use of regenerated tissue for drug testing and poison testing is also considered to be a research hotspot in the next 5-10 years, which will also bring revolutionary breakthroughs to the biomedical industry.

(Human-on-a-chip drug testing model, Credit: Wyss Institute, Harvard University)

Reference:

1.

2.

The Laboratory for Tissue Engineering and Organ Fabrication

3.

Langer Lab: Professor Robert Langer

4.

/tags/tissue-engineering

(recommended reading)

6.

(recommended reading)

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