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The Basis for Avoiding the Inflammatory Response in Wound Healing

posted in Inflammation by


For decades conventional wisdom in skin rejuvenation has postulated that an inflammatory response to accomplish collagen induction is essential. It was believed that inflammation was needed to attract cells to the site of injury, such as neutrophils and macrophages, which, in turn, release growth factors and cytokines responsible for repair. Clearly, the wound healing cascade does cause repair that may appear to be positive from a cosmetic perspective. However, given the overwhelming evidence in all other systems in the body that inflammation is to be avoided at all costs, why would this not hold true for skin as well? Inflammation is linked to arthritis, heart disease, strokes and cancer, and forms the very basis for aging.

The scientific evidence to support a paradigm shift includes the following:

Inflammation is absent in the embryo wound healing model for skin. Therefore, we can reasonably conclude that inflammation is not a necessary process or requirement for repair or “rejuvenation”.

Scarring is absent in embryo wound healing. All evidence in research points to scarring and destruction of normal tissue being the result of the inflammatory response.

Classic examples of a prolonged inflammatory response include severe burns and chronic leg ulcers. Scarring in these individuals is exaggerated, which begs the question of why we would want to provoke and prolong the inflammatory response in skin rejuvenation? Mimicking this model of wound healing does not make sense given the outcome. Yes, these are extreme cases demonstrating obvious outward signs of the process. Just because we cannot see outward evidence of a negative outcome does not mean that it is not present. In addition, negative outcomes may take decades to evolve, e.g. skin cancer after UVR. The long-term effects of light-based heat therapies are still unknown.

Fibroblasts can produce scar tissue or normal collagen, depending on the signals they receive that dictate their response or function. Inflammatory growth factors and cytokines induce scar tissue. Yes, one will get a result that can be viewed as cosmetic improvement. Given the fact that one can also get a result where normal collagen is produced by stimulating non-fibrotic or non-inflammatory growth factors and cytokines with less aggressive microneedling, why would we settle for anything less?

In our quest to produce collagen, it makes sense that we would avoid anything that breaks it down. The role of collagenase is well documented in this process. It is produced after any injury with two main peaks, the first within 1-7 days depending on degree of injury (to remove any non-viable tissue after injury), and the second at around day 14 (to re-organize the wound collagen). With this knowledge, inducing this enzyme repeatedly by provoking the inflammatory response any more frequently than the natural 28-day healing cycle will result in a permanent state of peaked collagenase which will be counter-productive to our goal.

In summary, provoking and prolonging the inflammatory response, while achieving a short-term cosmetic result, ignores the long-term consequences, and may well be deemed below best standard of care, or even “negligence”, in the near future.

25 May, 15

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There are 2 comments. on "The Basis for Avoiding the Inflammatory Response in Wound Healing"


  • ***Suzanne Pear*** says: posted on 23 Jun, 2015

    Dr. Setterfield,
    Would you mind elaborating on how one should avoid the inflammatory response in wound healing? Are you referring to avoiding medical needling (depth >0.5mm) or frequency <28 days, or ?? Microneedling, to me, is very similar to Proliferative Therapy which is increasingly being used to repair joint and vertebral injuries or degeneration. An irritating solution or PRP is injected into the area of concern and the area is then needled, all in the hopes of initiating an inflammatory response, which in turn will rebuild the lost collagen in the area. It is recommended that anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen and naproxen not be used for at least a week after the treatment so as not to mute the body's response to this injury. Repeat treatments are performed no sooner than every 4 weeks. The improvements many people notice from this therapy are remarkable. Thanks for the clarification.

    • ***Dr. Lance Setterfield*** says: posted on 26 Jun, 2015

      As you point out, inflammation is influenced by both timing of treatments and depth of microneedling.

      Treatments performed any more frequently than 28 days will provoke and prolong the inflammatory state.

      Cosmetic microneedling (depth less than 0.5mm) triggers a different regenerative pathway with very limited inflammation. Injury to keratinocytes upregulates genes for the production of Collagen Types III and VII at the dermal-epidermal junction.

      Medical microneedling (depth more than 0.5mm) involves platelets. The growth factors in alpha granules found in platelets (VEGF, PDGF, TGF-B1 and TGF-B2) are all inflammatory. One of the roles of TGF-B1 and TGF-B2 is to promote rapid re-epitheliazation. Thus, it is true that PRP results in “faster” wound healing. But what long-term effect do we desire? Normal collagen or scar collagen? As mentioned in my original article, inflammation is the basis for virtually all diseases known to afflict us. Inflammation causes premature aging. Inflammation recruits myofibroblasts into a wound to mass-produce collagen during a state of emergency. The quality of collagen is not the same as that which is produced under normal day-to-day regeneration to maintain our largest organ.

      The use of PRP in sport medicine and dentistry relies on the very fact that chronic inflammation results in scar tissue that provides added strength where loss of structural integrity has occurred. Scar tissue in a torn ligament is a good thing in order to provide joint stability. PRP also encourages bone growth and cartilage repair. A fibroblast in a knee joint is quite different to one that exists in the face. It is the growth factor/cytokine signaling system that instructs the fibroblast how to behave….keratinocyte cross-talk signals them to make collagen in the face and platelets trigger inflammation in the joint to recruit fibroblasts and dictate cartilage production in the knee. Same name (fibroblast), different functions, depending on location in the body….all determined by growth factor/cytokine profile. Some similarities in aspects of healing pathways, but not comparable end-points.

      Yes, PRP/PRF may offer results faster. The question is whether or not the results are superior to microneedling combined with the correct topical products and other treatments like LED to limit the inevitable inflammatory process as much as possible. Further studies are needed to finalize this debate.


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