From Chapter 4. The Matrix and Wound Healing: Template for Healing Matrix Injury Understanding the processes and components involved in the self-healing of wounds and traumas not only facilitates our comprehension of how the matrix builds and repairs itself, but helps us learn how to treat the ECM in a knowledgeable fashion. A review article by Olczyk et al. (2014) gives an excellent overview of the subject. The authors traced out the role of ECM constituents in the progress of wound healing. These constituents play significant roles in hemostasis (stopping bleeding) and each of the three stages of healing: inflammation , granulation , and remodeling . The whole process includes the building of new "scaffolding," or a "provisional new matrix," various repair processes, with signaling and regulation during "this dynamic, interactive sequence." These same processes apply when toxins, microbes, internal wounds, etc.

, attack the matrix--though the bleeding stage will not generally occur. The Three Stages of Healing Three fundamental stages of healing have long been recognized. They overlap but also follow one another in sequence. The processes associated in a stage can be overactive or underactive, so that the organism gets stuck and that blocks the later stages from occurring. For instance, no granulation (cell proliferation and regrowth) will occur as long as the area is inflamed. Excessive granulation (commonly called "proud-flesh") will block the next stage, including the formation of a healthy scar signaling the end of the process. The Inflammatory Stage Inflammation develops during the first 24 hours after an injury has occurred and lasts on average for up to 48 hours in a modest wound. The characteristic symptoms of inflammation--established since the doctors of ancient Rome--are redness ( robur ), heat ( calor ), swelling ( tumor ), and pain ( dolor ).

(Sounds better in Latin.) The inflammatory stage is initiated by neutrophils--the first pro-inflammatory cells to appear at the wound site--and continued by macrophages, the consumers of bacteria and debris. Neutrophils and macrophages are the first line of defense against infections, consuming invading bacteria and the proteases they release, and the debris from injured tissue. They intensify the inflammatory reaction by releasing pro-inflammatory cytokines. They also generate reactive compounds containing oxygen and nitrogen that encourage and control oxidative processes. Thrombin and products of fibrin decomposition, bacteria, cytokines, and leukotrienes control neutrophil and macrophage behaviors. All of these are attracted to the place of damage by various means. Neutrophils and macrophages not only initiate the inflammatory stage but release cytokines and growth factors (GFs) that activate fibroblasts and epithelial cells that create conditions for the initiation of the next phase of the healing process: granulation (Olczyk, et al.

, 2014). Bacteria arrive early at the scene as scavengers living off debris. They produce various kinds of proteases (enzymes that break down proteins) in the course of their work. These act on both the matrix itself and the cells. They increase the virulence of infection, degradation of tissue, and encourage the evasion and destruction of physical barriers to bacterial invasion. Some of them secrete the enzyme hyaluronidase that breaks down HA, retarding repair and facilitating the spread of bacteria. They also secrete the enzymes collagenase and elastase to break down connective tissue fibers and perpetuate the invasion. These activities spread the bacteria through the matrix, furthering the inflammatory response.

Other bacterial enzymes generate free radicals that cause additional inflammation and tissue degradation through uncontrolled oxidation. Neutrophils and macrophages need to contain and remove the bacteria, their proteases and enzymes, not only to bring the inflammatory stage to an end but to prevent mutation in the DNA of cells and damage to the matrix, both of which can encourage the eventual appearance of cancer (Alfano, et al, 2016). After two- or three-day presence in the wound area, the neutrophils are depleted by apoptosis (built-in self-destruction) and replaced by monocytes that migrate from the capillaries into the matrix, where they are transformed into macrophages under the influence of inflammatory mediators--byproducts of fibrin and fibronectin degradation and other factors coming from the temporary wound matrix. Remedies that act on the four symptoms of inflammation are well known in herbal medicine. A full range would include those for an overactive immune response as well as those for an underactive response. An incomplete list are given under the remedies for Mast Cell Instability, while a few of the latter ( Calendula, Echinacea ) are listed here. Native Americans use saps and resins to seal off, sanitize, and heal wounds. Dr.

Marguerite Maury (see final chapter), considered such resins and dense essential oils to be especially active on the matrix. As a class, the herbs used here possess or combine these sedative or stimulating properties with mucilage. Calendula officinalis This plant medicine comes to us from central European folk medicine via homeopathy. It is used in homeopathy in herbal doses, externally, for wound-healing. The flowers are used, including the petals (which are slightly sweet and mucilaginous) and the corollas or flower base (which are bitter and salty). It is said in many herbal websites and books (I used to say this) that Calendula contains iodine. However, modern assays do not bear this out. What does seem to be true is that Calendula picks up iodine.

This is indicated by the fact that it was used, a hundred years ago, to detect the presence of iodine. Calendula tincture turns red in the presence of iodine - research by Phyllis Light. This means that there is a chemical reaction between Calendula and iodine. Since there is already iodine in the body, this means that the plant picks up available iodine. This naturally produces the powerful topical or local healing formula discovered by Dr. Cutting--iodine and hyaluronic acid (or mucilage) and now available as a product called Hyiodine. Calendula is used for all kinds of surface injuries, cuts, and wounds. It does not have the reputation of Yarrow as a hemostatic.

It is best suited to swollen, red, inflamed, painful tissues that are not open where pus is building up inside (think of a cat scratch). From experience we can deduce that Calendula helps with the drainage from the wound through the lymphatics. It is an excellent remedy for swollen lymphatics independent of a wound, especially old, stagnant cases needing mild stimulation. But it manifests its herbal genius when there is a surface wound. Calendula is considered a "bacteriostatic," meaning that it does not kill bacteria but stabilizes the population of microbes as the wound heals. This means it does not interfere with the natural healing processes associated with natural immunity - which, as we saw above - are very finely tuned by changing sequences of immune cells. The havoc wrecked upon the system by antibiotics (more so when taken internally) is impossible to estimate. We know that they destroy the gut flora, leading to almost untreatable conditions like small intestine bacterial overgrowth (SIBO).

We do not know exactly what Calendula does, but clearly it assists in the removal of pus and the lay-down of the new "scaffolding" consisting of matrix polymers analogous to those found in the Calendula petals, also probably having an encouraging or regulatory effect on immune cell activity. At any rate, it is the single most important wound-healing medicine in herbalism. The Proliferation or Granulation Phase This is the phase in which proliferation of cells occurs so that new connective tissue, epithelium, and endothelial vessel tissue can be laid down. It is also frequently called "granulation" because the newly laid down capillary bed tufts look like granules. This combination of proliferating cells makes a tissue that is unformed and pink. The work of regrowth and replacement is synergistic as fibroblasts synthesize new ECM components in the presence of newly formed blood vessels manufactured by endothelial cells migrating and proliferating to close up the wound. Aloe barbadensis (Aloe vera) This succulent has been used in medicine since ancient times. The layer under the external rind contains a yellow substance rich in anthroquinones that is cathartic, while the inner gel contains 99% water mixed with glucomannans (akin to matrix polysaccharides), amino acids, lipids, sterols, and vitamins.

The gel has been used in folk medicine as a wound-medicine and burn remedy. It is excellent for burns, used in a spray freshly prepared from the gel and water, notes herbalist Steven Horne.