Healing is the desired outcome of inflammation. A successful inflammatory response resolves injury or infection by rapid elimination of bacteria or foreign bodies, by repairing damaged tissue with connective tissue, and by saving the tissue's ability to function. Healing differs from simple repair in that healing involves regeneration of parenchymal tissue while repair by connective tissue does not. The best healing occurs when the inflammatory response has been quick and effective, resulting in minimal tissue damage.
The process of healing begins very soon after inflammation starts. It is not uncommon for inflammation to occur at the same time as healing, with neutrophils and macrophages engaged in their struggles right next to fibroblasts that are laying down collagen. Because inflammation and healing can occur simultaneously, it can be difficult to figure out exactly how well an injury is resolving. Oftentimes the injury will not resolve well, especially if the inflammatory stimulus is strong and ongoing. Chronic inflammation typically results in dense connective tissue throughout the wound area and can lead to encapsulated abscesses or heavy scarring.
In order to describe clearly the process of healing, we will consider the idealized example of healing by first intention. Healing by first intention describes healing that occurs in surgical wounds that have been closed with sterile suture. They are clean wounds and are (or, at least, had better be) aseptic, so the inflammation does not involve infection.
Within 24 hours of the incision, neutrophils will infiltrate the affected area and begin their jobs of phagocytosis and elaboration of cytokines. Phagocytosis, obviously, clears out any bacteria and foreign bodies, and the cytokines summon more neutrophils and macrophages. The cytokines also stimulate the creation of new blood vessels and, in certain cases, increased mitotic activity in parenchymal cells. The new blood vessels provide nutrients for the migrating fibroblasts as well as scaffolding for tissue repair. This stage of healing lays the groundwork for repair and lasts for approximately 48 to 72 hours.
After about three days, fibroblasts appear on the scene and begin to elaborate collagen. Prior to this stage, the wound is held together only by the sutures and by a thin layer of fibrin that exudes from the wounded vasculature. The fibroblasts provide the connective tissue that is necessary truly to repair the wound. Collagen is first laid down at the margins of the wound and is organized over several days into strands that bridge the gap and close the wound.
At this stage of the process, the wound is filled in by new blood vessels and collagen, a combination called granulation tissue. Granulation tissue appears bright pink and glossy since it is mostly thin blood vessels and thin sheets of connective tissue. Over time the granulation tissue will keratinize and become tougher. It will also lose its bright pink color and come to look like the normal tissue around it. Unless the wound has been apposed most perfectly, there will be some amount of obvious connective tissue showing, a condition we call a scar.
After about two weeks, inflammation should all but disappear. Collagen remodeling will occur for some time afterward, up to several months,depending on how extensive the damage was. Regions of scarring become stronger over time, but they will never achieve the same strength as the original tissue. Tensile strength of 70 percent of normal is about the greatest one could expect.
HEALING BY SECOND INTENTION
Healing by second intention describes the process of healing a wound without the benefit of surgical closure. In this case, the wound is allowed to "granulate in", that is, the wound closes by contraction and filling with connective tissue.
The basic process of healing by second intention is approximately the same as healing by first intention. The major differences are that wounds healing by second intention are more open and are more prone to infection, and that much more granulation tissue is necessary to close the wound. Furthermore, while the timing of the appearance of the various cell types is the same in both cases, healing by second intention will take longer simply because there is a larger wound to fill.
The greatest problem faced by the by the body when healing by second intention is how to close the gap in the wound with connective tissue. Fibroblasts arrive on the scene but they cannot bungee-jump across the wound to close it, so how does the wound heal? In this case, some of the fibroblasts will become myofibroblasts and acquire the ability to contract in synchrony with one another. The myofibroblasts act together to contract the edges of the wound, thereby bringing the margins closer together and facilitating healing.