What is tissue regeneration and repair?

Tissue regeneration involves the restoration of tissue components by regrowth of damaged tissues. In contrast, tissue repair involves patching of injured tissue rather than restoring it. It is the proliferative capacity of the cells that decides the amount of regeneration against the repair that would occur in the tissue. Both regeneration and repair depending on the duration of the injury and response to the inflammation.

Process of regeneration

• The proliferation of differentiated parenchymal cells. Parenchymal cells are capable of cell division and thus divide to increase their number, which eventually results in regeneration and wound healing. For example, hepatocytes which are the epithelial cells of the liver.

• The stem cells also play an important role in tissue regeneration. Stem cells are the cells that have the ability to differentiate into specialized cells performing specific functions. For example, surface epithelia and intestinal tract.

Types of cells

Depending on the cell's ability to divide, the body cells are classified into three types.

Labile cells

These cells are continuously dividing cells with a short lifespan. They undergo continuous division by producing stem cells that further differentiate and proliferate to replace the dead cells. For example, hematopoietic cells in bone marrow, majority of surface epithelia, cells of lymph nodes, the stratified squamous epithelium (which is lining the oral cavity, cervix, vagina skin), the columnar epithelium (lining the gastrointestinal tract, uterus, fallopian tube), the cuboidal epithelium (lining the ducts driving the exocrine gland like the salivary gland) and the transitional epithelium (lining the urinary tract).

Stable cells

These cells are quiescent. They are in the G0 phase of the cell cycle. They have minimal proliferative activity in a normal state. But if there is injury or loss of tissue mass, they enter into the cell cycle according to the cell's requirement and they start to proliferate. For example, the majority of parenchymal cells in organs like kidney, liver, pancreas, fibroblast endothelial cells, and smooth muscles (they play an important role in wound healing).

Permanent cells

These cells are terminally differentiated and nonproliferative in postnatal life. They have lost their ability to divide or proliferate from the beginning of their life. Examples include neurons, heart myocytes, skeletal muscles.

Mechanism of tissue regeneration

In labile cells, the damaged cells are replaced by the normal cells by the proliferation of the cells or stem cells. During cell division, the parent cell divides into two daughter cells, of which one cell becomes the stem cell. When cells or tissue is damaged, the stem cells start differentiating to produce new cells. After that, they start to migrate and cover the gap. Then the migrated cells proliferate following differentiation and maturation.

Steps of tissue repair

Replacing damaged tissue with fibrous tissue. It involves three processes.

1. Granular tissue formation
2. Contraction of wounds
3. Wound healing

1. Granular tissue formation

Granular tissue formation involves the formation of new connective tissues and blood vessels on the damaged surface. It involves three phases: phase of inflammation, phase of clearance, phase of ingrowth of granular tissue.

Phase of inflammation

In this phase after trauma or blood clot at the site of the origin, there is an acute inflammatory response following the release of plasma, neutrophils, and some monocytes.

Phase of clearance

In this phase combination of different types of proteolytic enzymes liberated from neutrophils and along with the liberation of autolytic enzymes from the dead tissues and the phagocytes nature of the macrophage, helps to clear off the necrotic tissue, debris, and red blood cells.

The phase of ingrowth of granular tissue

There are two major processes involved in this phase.

• Angiogenesis
• Fibrogenesis

Angiogenesis

This process of formation of new blood cells. It plays an important role in providing nutrients and oxygen, which is necessary for the repair process.

Several factors play an important role in this process like the vascular endothelial factor (VEGF), which is present only in endothelial cells, platelet-derived growth factor (PDGF), transforming growth factor-B (TGF-B), basic fibroblast growth factor (bFGF), and the surface integrins which helps in cellular proliferation.

Fibrogenesis

In this process, the fibroblast originates from the fibrocytes and as well as from the mitotic division of the fibroblasts in the newly formed blood vessels. Collagen fibrils start to appear by about the sixth day. As the maturation proceeds, the number of collagen increases, whereas the number of active fibroblasts and the new blood vessels also decreases. This leads to the formation of an inactive form of scar known as cicatrization.

2. Contraction of wound

This phase starts after 2-3 days and takes the time of 14 days to complete. During this phase, the size of the wound decreases day by day just because of the contraction of myofibroblasts which leads to rapid healing.

3. Wound healing

The classic example of the combination of regeneration and repair is the healing of skin wounds.

The healing process can occur in one of the following two ways depebding on the type of wound.

1. Healing by primary intention
2. Healing by secondary intension

Healing by primary intention (primary union)

It is also referred to as primary closure. It involves the healing of injuries or wounds whose edges are close or defined, such as in the case of surgical incision. In this type of healing, the restoration occurs in continuity which requires the development of few connective tissues and blood vessels on the damaged surface and reduced scar formation.

The sequence of events in the primary union or intention includes initial hemorrhage, acute inflammatory response, proliferative phase and remodeling.

Initial hemorrhage

Immediately just after the injury, there is a gap or space between the wound that is filled with blood which then clots and helps to seal the wound.

Acute inflammatory response

This occurs in a short period of 24 hours which involves the movement of leukocytes to the site of injury from the blood. It helps in the removal of cellular debris and pathogenic agents.

Proliferative phase

During the proliferative phase, the wound is filled with an extracellular matrix and the new blood vessels develop. Fibroblasts are the connective tissue cells that synthesize and secrete collagen, growth factors that induce the growth of blood vessels through a process known as angiogenesis while promoting endothelial cell proliferation and migration. The fibroblasts and the endothelial cells help in the formation of granulation tissue which acts as the foundation for scar tissue development.

Remodeling

In this stage, the final tissue is formed by the simultaneous synthesis of collagen. Collagen fibers begin to settle in the wound and provide strength in the area, followed by apoptosis of fibroblasts.

Thus, the ultimate outcome of primary intent healing is primarily a complete return to function, with minimal scarring and loss of skin appendages. In this stage, final tissue is being formed by the simultaneous synthesis of collagen

Healing by secondary intention (secondary union)

Secondary intent healing occurs when the sides of the wounds are not opposed, having a severe cell loss.

The basic events in the secondary union are quite similar to the primary union, but as in the case of the secondary union, there is considerable tissue damage that has to be bridged.

The sequence of events in the second union includes initial hemorrhage, acute inflammatory response, proliferative phase and remodeling.

Initial hemorrhage

Immediately just after the injury, there is a gap or space between the approximated surfaces of the incised wound that is filled with the blood, which then clots and helps to seal the wound.

Acute inflammatory response

An inflammatory response acts to remove the cell debris and pathogens. As in the secondary union, there is a huge amount of debris, so the inflammatory reaction tends to be more intense and highly active than the primary intention.

Proliferative phase

This is the most important step, granulation tissue forms at the bottom of the wound. The epithelia can only take part in the proliferation and regeneration once the granulation tissue fills the wound to the level that matches the original epithelium. As soon as the granulation tissue reaches this level, the epithelia completely cover the wound. So, the epithelial and granulation tissue play an important role in covering or healing the wound.

Remodeling

In this phase, the inflammatory responses begin to resolve, which leads to the contraction of the wound.

Factors influencing wound healing

Local factors

• Infection
• Very poor blood supply
• Foreign bodies and contamination
• Type, size, and the site of origin of an injury

Systematic factors

• Age
• Nutritional deficiency, mainly Vitamin C
• Obesity
• Haematologic abnormalities

Roles of myofibroblasts in secondary intention

Myofibroblasts play an important role during wound healing by secondary intention. As they are the modified form of the smooth muscle cells that contain actin and myosin protein, they help in the contraction of the wound by decreasing the space between the dermal edges. They also help in the deposition of collagen, which helps in scar healing.

Differences between primary intention and secondary intention

• In primary intention, the inflammatory reaction is less, whereas, in the secondary intention, there is an intense inflammation
• No wound contraction occurs in the primary intention, whereas, in the secondary intention, granulation tissue formation is more compared to the primary intention.
• In the case of primary intention, there is minimal tissue damage, but in the case of the secondary intention there is remarkable damage in the tissue.
• The primary intention is the process of rapid healing, whereas, secondary intention is slow healing.
• The complication rate in the case of primary intention is minimal, but in the case of secondary intention, the complication rate is so high.
• There is a small scar in case of primary intention, whereas, there is a large scar in the case of the secondary intention.

Difference between regeneration and repair

• Regeneration is the type of healing, whereas repair is the restoration of tissue structure and its function after an injury
• The result of the regeneration is the complete restoration of the original tissues, but in the case of repair, it results in fibrosis and scarring.

Context and applications

This topic is very helpful and significant in the professional exams for both undergraduate and graduate courses, especially for

• Bachelors of Science in Zoology
• Bachelors of Science in Anatomy and physiology
• Masters of Science in Zoology
• Masters of Science in Anatomy and physiology

Practice Problems

Q 1. Which of the following is included in the primary intention of wound healing?

1. rapid healing
2. slow healing
3. wound contraction
4. maximum tissue damage

Answer-a

Explanation- Primary intention is the process of rapid healing, whereas the secondary intention is slow healing. So, the correct answer is rapid healing.

Q 2. Which of the following is included in the secondary intention of wound healing?

1. the complication rate is minimal
2. the complication rate is high
3. rapid healing
4. small scar

Answer-b

Explanation- The complication rate in the case of primary intention is minimal, but in the case of secondary intention, the complication rate is high. So, the correct answer is that the complication rate is high.

Q 3. Regeneration is a process of which of the following?

1. healing
2. restoration
3. inflammation
4. destructive

Answer-a 

Explanation- Tissue regeneration means the regeneration of the injured cells. So, healing is the correct answer.

Q 4. Which of the following is the function of fibroblasts?

1. promote the growth of blood vessels
2. promote cell division
3. breakdown scar tissue
4. inflammation in tissue

Answer- a

Explanation- Fibroblasts are the connective tissue cells that synthesize and secrete collagens. They also secrete growth factors that induce the growth of blood vessels. So, the correct answer is to promote the growth of blood vessels.

Q 5. Angiogenesis is the process of which of the following?

1. formation of new blood cells
2. formation of fibrous tissue
3. myofibroblasts
4. macrophages

Answer-a

Explanation- Angiogenesis plays an important role in providing nutrients and oxygen, which is necessary for the repair process and the formation of new blood cells. So, the correct answer is the formation of new blood cells.

Related Concepts

• Medicine biology

• Microbiology

• Developmental biology