[0:04]Wound healing is the process where the body repairs damaged tissue after any traumatic injuries, anything from a paper cut to a stab wound. Acute wounds heal quickly over days to weeks, whereas chronic wounds like bed sores, foot ulcers, or infections can persist for months. Now, some tissues regenerate more easily than others, and the regenerative capacity of tissue is classified as labile, stable, and permanent. Labile tissues like skin, connective tissue, and small and large intestine heal extremely well, because they contain stem cells, which are undifferentiated cells that can divide and renew the cells that have died. Stable tissue, like the liver, recover from injury by having mature differentiated cells divide or regenerate via hyperplasia. Permanent tissues like skeletal muscle, cartilage, neurons, and cardiac tissue have a weak regenerative capacity because they lack these stem cells and cannot replicate via hyperplasia. Typically, injured permanent tissues are replaced by scar tissue or fibrosis, ultimately resulting in loss of function of the tissue.
[1:21]Now, when it comes to the skin, which is often the most visible tissue that's damaged, wound healing occurs by primary, secondary, and tertiary intention. Healing by primary intention is when the wound edges come together, like what happens when two wound margins are stitched or sutured together. When this happens, stem cells in the epidermis or uppermost layer of skin are brought close together and can regenerate the damaged tissue near the surface of skin, leaving a minimal scar. Healing by secondary intention occurs when the wound edges are too far from one another, and this can be a consequence of significant tissue loss or if there's an object embedded in the wound that prevents the edges from coming together. Examples of healing by secondary intention include tooth extraction sockets or severe burn injuries. Since the stem cells in these wounds do not approximate, the wound is replaced primarily by connective tissue that grows from the base of the wound upwards. Healing by tertiary intention or delayed closure is when a wound is cleaned and purposefully left open due to a high likelihood of being contaminated by bacteria, like during a dog bite injury. If these wounds are closed too early by primary intention, they can trap bacteria inside the wound, leading to an abscess or walled-off infection. Instead, these wounds are left open, cleaned, and observed for several days before they're closed by primary intention, or left open to heal by secondary intention.
[2:56]Now, to explain the steps of wound healing, let's imagine that you're cutting a banana cream pie and you accidentally slip and cut your finger. Ouch. During a penetrating injury like this, the skin is punctured through the top two layers of skin, the epidermis and the dermis. When this happens, damage occurs to both the cells found in these layers and the area between the cells, called the interstitial space. The interstitial space contains proteins outside of the cell that act like scaffolding between cells. So, when this is damaged, the cells separate, forming the open wound. Now, the first step of wound healing is hemostasis. And that's where a blood clot forms at the site of trauma to prevent further blood loss. Hemostasis starts when blood vessels affected by trauma constrict. Platelets, which are tiny blood components involved in coagulation, immediately aggregate around the affected tissue and stick together to form a platelet plug. The platelet plug is further reinforced by a protein mesh called fibrin, which ultimately forms the blood clot.
[4:05]Once an adequate blood clot has formed, the second step of wound healing begins, and that's inflammation. Damaged cells release tiny proteins called chemokines and cytokines, which recruit immune cells like macrophages and neutrophils to the area, and make nearby blood vessels dilate and become more leaky and permeable. Immune cells start to seep into the affected area and they begin to clear foreign debris like dirt and digest dead or damaged cells caused by the injury as well as destroying any microbe that may have gotten in. At the end, there's a blood clot and dead macrophages that have consumed damaged cells and other debris, and this forms a scab, our body's own bandage. Now, the third step of wound healing is epithelization or migration, which is where basal cells or the stem cells in the epidermis start to proliferate in order to replace the lost or damaged cells. This process takes about 48 hours and ends when the epidermal layer is rejuvenated. But this newly formed epidermal layer is still kind of weak because the strong dermal layer below hasn't yet regenerated. The fourth step of wound healing is called fibroplasia, and that's where the wound becomes stronger and damage resistant. During this step, fibroblasts in the dermis proliferate and secrete a long fibrous protein called collagen in a process called fibroplasia. Collagen proteins assemble to form fibrils, and collagen fibrils assemble to form collagen bundles, which have high tensile strength, and it acts as the extracellular scaffolding that holds together the newly formed epidermal cells. Collagen also stimulates new blood vessels to grow in the area, a process called angiogenesis. Fibroblasts also produce proteins called glycoproteins and sugars that make up the ground substance or cement between the cells in the wound. So, fibroplasia results in the creation of granulation tissue, which is the red tissue that lies below the scab in the newly regenerating dermal layer. The final phase of wound healing is termed maturation, which is where the wound gets a job. I'm kidding, it's where the wound gets even more physical support, and there are a few steps in maturation. First off, there's collagen cross-linking, which is where covalent bonds form between collagen bundles. This helps to enhance the tensile strength of the wound. Next, there's collagen remodeling, which is where fibroblasts degrade old or misshapen collagen from the injury, like when old rotten wooden beams are replaced before putting up new ones in a house. After that, there's contraction, which is when special fibroblasts called myofibroblasts produce contractile proteins within the cell. These contractile proteins are attached to transmembrane proteins, which are attached to proteins in the interstitial space. So, when contractile proteins in the cell tighten, they pull on those proteins in the interstitial space, ultimately pulling the edges of the wound together. This step is particularly important in large wounds that must heal by secondary intention. Finally, there's the step of repigmentation, which is when melanocytes begin to proliferate and that helps restore the normal color to damaged skin. Now, there are some factors that prevent proper healing and can lead to chronic wounds. For example, when the smallest blood vessels, called capillaries, become narrowed by some disease process, blood flow decreases. When this occurs, the wound cannot heal properly because fewer immune cells are getting to the damaged tissue, and the damaged tissue has a hard time getting nourished by oxygen and nutrients needed for repair. Since the tissue cannot repair itself, it undergoes necrosis where cells die prematurely. Some common causes of decreased blood flow include diabetes, atherosclerosis, and prolonged compression. Infections can also interfere with healing, and that's because pathogens compete for oxygen and cause ongoing damage and inflammation in the tissue. Finally, uncontrolled swelling or edema around the wound can disrupt fibroblast activity and collagen deposition and cross-linking of collagen. All right, as a quick recap. When damage occurs to tissue, healing proceeds through a predictable set of stages that include hemostasis, inflammation, epithelialization, fibroplasia, and maturation. Wounds can heal by primary intention, where the wound edges are brought together, or secondary intention, where the edges are far apart. Wound healing can also occur by tertiary intention where the wound is left open to prevent infection. Some things that can impair wound healing include diminished blood flow, infections, and swelling.
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