Most people think of sun damage as brown spots, wrinkles, rough skin, and uneven skin tone.
But sun damage goes much deeper than what we can see in the mirror.
Years of ultraviolet, or UV, radiation can change the way skin cells behave. It can damage collagen, alter the extracellular matrix that supports the skin, increase abnormal inflammation, cause some fibroblasts to become old or “senescent,” disturb communication between cells, and damage DNA.
This is why CO2 laser resurfacing is more interesting than simply “removing the top layer of skin.”
A CO2 laser creates a carefully controlled injury that starts a complex biological repair process. During this process, the skin removes damaged material, activates repair proteins, makes new collagen, reorganizes its extracellular matrix, recruits immune cells, and may restore healthier communication between the dermis and epidermis.
In other words, the treatment does not simply polish the skin.
It causes the skin to remodel itself.
Modern research helps us understand how this happens.
First, What Does Sun Damage Actually Do to the Skin?
Sunlight contains ultraviolet radiation. UVA and UVB radiation can both contribute to skin aging, although they affect the skin in somewhat different ways.
Repeated UV exposure produces oxidative stress and damages cellular DNA.
Over many years, this can lead to:
Brown spots and uneven pigmentation
Rough skin
Fine lines and deeper wrinkles
Loss of elasticity
Broken collagen fibres
Abnormal elastic fibres
Reduced collagen production
Chronic low-grade inflammation
Changes in fibroblast function
Accumulation of senescent cells
DNA mutations
Actinic keratoses and, eventually in some people, skin cancers
One of the biggest changes happens in the extracellular matrix, or ECM.
What Is the Extracellular Matrix?
The extracellular matrix is the support system surrounding the cells in our skin.
Imagine building a house.
The cells are like the people living inside the house, while the extracellular matrix is the framework, floor, walls, beams, and support structure around them.
The skin’s extracellular matrix contains substances such as:
Collagen
Elastin
Fibronectin
Proteoglycans
Glycosaminoglycans such as hyaluronic acid
Collagen gives skin strength.
Elastin allows it to stretch and return to its original shape.
These structures also help skin cells communicate with their surroundings.
In young, healthy skin, fibroblasts are surrounded by an organised network of collagen. They attach to this matrix, stretch across it, and continue producing proteins needed to maintain the dermis.
In heavily sun-damaged skin, this structure becomes fragmented and disorganised.
The fibroblasts therefore receive different mechanical and chemical signals.
Over time, the entire system becomes less efficient at maintaining healthy skin.
How Does a CO2 Laser Start the Repair Process?
A CO2 laser produces light at a wavelength of approximately 10,600 nanometres.
Water absorbs this wavelength extremely well.
Because the skin contains a large amount of water, the laser’s energy is absorbed by water within the tissue. This rapidly heats very small areas of skin.
With a fractional CO2 laser, the laser creates thousands of microscopic columns of controlled injury while leaving untreated skin between them.
These are sometimes called microscopic treatment zones or microscopic ablation zones.
The untreated skin surrounding these tiny columns helps the area heal.
But the important part is what happens next.
The laser injury activates a wound-healing response involving inflammatory cells, fibroblasts, keratinocytes, growth factors, heat-shock proteins, enzymes and extracellular-matrix proteins.
A 2026 review of studies investigating ablative laser treatment found that both fractional and fully ablative lasers produce a coordinated response involving inflammation, breakdown of damaged matrix, collagen production, elastin remodelling and longer-term dermal reconstruction.
The First Stage: Cleaning Up the Old Extracellular Matrix
One of the most interesting parts of CO2 laser treatment is that the skin does not immediately begin by simply making more collagen.
First, it has to clean up some of the damaged collagen already there.
This involves enzymes called matrix metalloproteinases, usually shortened to MMPs.
What Are Matrix Metalloproteinases?
MMPs are enzymes that can cut apart proteins within the extracellular matrix.
You can think of them as a biological demolition and recycling crew.
Some important ones include:
MMP-1: breaks down major fibrillar collagens.
MMP-3: helps break down several components of the extracellular matrix.
MMP-9: helps remove damaged matrix and basement-membrane material.
MMP-13: also participates in collagen turnover and remodelling.
A human study specifically examining photodamaged skin after fractional CO2 resurfacing found significant increases in several MMP genes, including MMP-1, MMP-3, MMP-9 and MMP-13. Researchers also found increases in MMP-10 and MMP-11.
This makes biological sense.
Before the skin can build a healthier framework, some of the old, fragmented matrix must first be removed.
Aren’t MMPs Bad for the Skin?
This is where the biology becomes interesting.
Chronic UV exposure can keep MMP activity abnormally high. Over many years, this contributes to collagen destruction and skin aging.
So chronically elevated MMP activity can be harmful.
But the short, controlled increase in MMP activity that occurs during wound healing serves a different purpose.
It helps remove damaged matrix so that new matrix can be built.
Think about renovating an old house.
You would not want a demolition crew tearing down walls every day for 20 years.
But you may need the demolition crew for a few days at the beginning of a renovation.
That is similar to what happens with MMPs after laser resurfacing.
The skin temporarily increases matrix breakdown, followed by a longer rebuilding phase.
Studies of fractional laser resurfacing show this organised sequence: inflammation and MMP activation occur first, followed later by collagen production and dermal remodelling.
The Second Stage: Building New Collagen
After damaged material is cleared away, fibroblasts begin rebuilding the extracellular matrix.
Several signalling molecules help control this process, including transforming growth factor beta, or TGF-β.
TGF-β helps activate fibroblasts and encourages collagen production.
Following ablative and fractional laser treatment, researchers have observed increases in collagen-related signalling and production.
A recent review found that collagen types I, III and VII can remain elevated for months after ablative laser treatment. New elastic-fibre formation has also been observed.
This helps explain something patients often notice:
Their skin may continue improving months after the redness and peeling have finished.
The visible wound heals relatively quickly.
The biological remodelling underneath continues for much longer.
Heat-Shock Proteins: The Skin’s Emergency Repair Proteins
Another important part of this response involves heat-shock proteins, or HSPs.
Despite their name, heat-shock proteins are not only produced because something becomes hot.
They are part of the body’s general cellular stress-response system.
When cells experience controlled thermal stress from a laser, certain heat-shock proteins increase.
Two groups are particularly interesting in laser resurfacing:
HSP70/HSP72
HSP47
HSP70 and HSP72
HSP70 proteins help protect stressed cells and assist other proteins in maintaining or recovering their correct structure.
You can think of them as part of the cell’s emergency repair team.
Human research has found increased HSP70 or its inducible form HSP72 following fractional laser treatment.
One human CO2 laser study found HSP72 as early as two days after treatment.
Another study found increased HSP70 only hours after fractional CO2 treatment, while HSP47 increased later.
This timing is important.
It suggests that different repair systems are activated at different stages.
HSP47: Helping Build Collagen Correctly
HSP47 has a more specialised relationship with collagen.
It acts as a collagen-specific molecular chaperone.
A molecular chaperone helps proteins fold and assemble properly.
Collagen is not simply produced and thrown into the skin. Its molecules must be correctly created, organised and assembled.
HSP47 helps with this process.
Human research with fractional CO2 laser has found that HSP47 increases after treatment and can remain elevated for months. One study found increased HSP47 beginning seven days after treatment and persisting three months later.
Another human study found that HSP47 peaked approximately one month after fractional CO2 treatment and remained elevated at three and six months. Researchers also observed new collagen and elastic-fibre formation during this period.
This is strong biological evidence that the effects of CO2 resurfacing extend far beyond the first few days of peeling.
CO2 Laser May Also Affect Cellular Aging
Another fascinating area of research involves senescent fibroblasts.
Fibroblasts are cells in the dermis responsible for producing much of the extracellular matrix, including collagen.
As fibroblasts age or accumulate damage, some become senescent.
A senescent cell is still alive, but it no longer behaves like a healthy younger cell.
Senescent fibroblasts can produce abnormal inflammatory signals and may stop producing normal amounts of important growth factors.
One particularly important growth factor is called IGF-1.
IGF-1: Communication Between the Dermis and Epidermis
IGF-1 stands for insulin-like growth factor 1.
In human skin, dermal fibroblasts are an important local source of IGF-1.
The IGF-1 produced in the dermis communicates with receptors called IGF-1 receptors, or IGF-1R, on epidermal keratinocytes.
Keratinocytes make up most of the epidermis.
This communication appears to be very important in helping keratinocytes respond correctly when ultraviolet radiation damages their DNA.
Research suggests that older skin contains more senescent fibroblasts and less locally produced IGF-1.
This means keratinocytes may receive less IGF-1 signalling.
And that may affect how they respond to UV damage.
Why Does IGF-1 Matter After UV Exposure?
When UV radiation damages DNA, a normal cell should not simply continue dividing as if nothing happened.
Ideally, it should stop and repair the damage.
If the damage cannot be repaired, protective mechanisms can prevent that damaged cell from continuing to multiply.
IGF-1 receptor signalling appears to be involved in this protective response.
Research has linked appropriate IGF-1R signalling with DNA-repair mechanisms, temporary slowing of DNA replication after UV damage, and protective cellular responses to seriously damaged cells.
This has led researchers to investigate whether resurfacing aged skin can restore more youthful fibroblast behaviour.
Can Fractional Laser Restore IGF-1?
There is interesting human evidence that it can.
An earlier human study found that fractional laser resurfacing reduced senescent fibroblasts, increased dermal IGF-1 expression and corrected an abnormal response to UVB seen in older skin.
More recently, a study specifically examining fractional CO2 resurfacing in 30 men with multiple actinic keratoses on the scalp reported approximately a 60% increase in IGF-1 expression in treated areas.
The treated areas also experienced a greater than 75% reduction in actinic keratoses during follow-up.
This is particularly interesting because it suggests that fractional CO2 treatment may change not only how skin looks, but also the biological environment in which epidermal cells live.
However, this area of research needs to be described carefully.
It does not mean that cosmetic CO2 laser treatment has been proven to prevent skin cancer in every patient.
The evidence is promising, but it is still developing.
An Important Study on Actinic Keratoses and Skin Cancer Risk
One of the strongest clinical studies in this area followed 48 adults over age 60 with extensive sun damage and multiple actinic keratoses.
Researchers treated only one arm with fractional ablative resurfacing, allowing the other arm to act as a comparison.
Over follow-up extending to 36 months, the treated arms developed substantially fewer actinic keratoses and fewer keratinocyte cancers.
There were 2 non-melanoma skin cancers recorded on treated arms compared with 24 on untreated arms. Researchers also found that the more appropriate response to UV exposure appeared to persist for at least two years.
There is an important detail, however.
This particular randomized trial used a 2790-nm ablative fractional laser, not a CO2 laser.
Therefore, it provides strong evidence for the biological concept of fractional ablative resurfacing and dermal renewal, but it should not be incorrectly presented as a CO2-specific randomized trial.
The smaller CO2-specific IGF-1 study provides supportive evidence, but larger CO2 trials would strengthen the conclusion.
CO2 Laser and Skin Homeostasis
Another useful way to understand laser resurfacing is through the idea of skin homeostasis.
Homeostasis means keeping a biological system in balance.
Healthy skin constantly has to balance:
Cell production
Cell removal
Barrier repair
Collagen production
Collagen breakdown
Hydration
Pigmentation
Inflammation
Immune defence
DNA repair
Communication between the epidermis and dermis
Sun damage gradually pushes this system away from its healthy balance.
For example, chronic UV exposure can:
Fragment collagen
Increase destructive MMP activity
Produce oxidative stress
Increase cellular senescence
Alter fibroblast signalling
Reduce normal collagen production
Create chronic inflammation
Damage keratinocyte DNA
Fractional CO2 laser causes a short, controlled disruption.
That may sound strange. Why damage the skin to repair damaged skin?
Because controlled wound healing can activate biological pathways that old, chronically sun-damaged skin is no longer using efficiently.
The treatment removes portions of damaged tissue, activates matrix turnover, recruits new fibroblast activity, stimulates growth-factor signalling and begins reconstruction of the extracellular matrix.
It is therefore reasonable to describe fractional resurfacing as creating a controlled regenerative response.
It does not literally return old skin to young skin.
But it can shift several biological processes toward a more organised pattern of repair.
What Happens to the Skin’s Immune System?
Skin is not simply a covering.
It is an immune organ.
It contains immune cells and produces signalling molecules and antimicrobial substances that help defend us from bacteria, viruses, environmental injury and abnormal cells.
Laser resurfacing affects this immune environment.
But saying that CO2 laser simply “boosts the immune system” would be scientifically inaccurate.
The response is more complicated.
First Comes Controlled Inflammation
Immediately after treatment, damaged cells release signals telling the body that repair is needed.
This attracts immune cells.
Studies have observed:
Neutrophils
Macrophages
T lymphocytes
B lymphocytes
Other inflammatory and repair cells
around fractional laser treatment zones.
Neutrophils arrive early.
They help clean up debris and damaged tissue.
Macrophages then play important roles in removing damaged material and coordinating later stages of wound healing.
Human CO2 laser research has shown increasing numbers of macrophages and giant cells around microscopic ablation zones during the days following treatment.
Natural Antimicrobial Defence Is Also Activated
Research has also shown changes in molecules that belong to the skin’s innate immune system.
For example, after ablative laser treatment researchers have observed increases in:
CXCL8, which helps recruit immune cells
CAMP, which produces the antimicrobial peptide cathelicidin
Human beta-defensin 2, or HBD2
These molecules participate in early immune defence and wound healing.
Cathelicidins and defensins are part of the skin’s natural antimicrobial system.
They help the body respond to microorganisms while a wound is healing.
However, these changes are temporary.
The inflammatory response usually decreases as healing progresses.
That is important because healthy skin does not want permanent inflammation.
The goal is:
activate → repair → resolve.
Not:
activate → remain inflamed forever.
Does CO2 Laser “Boost Skin Immunity”?
A more accurate statement would be:
Fractional CO2 laser temporarily activates local innate and adaptive immune responses as part of wound healing and may improve some aspects of the aged skin microenvironment.
That is different from claiming that it generally strengthens a person’s immune system.
In fact, during the first part of healing, the protective epidermal barrier has been disrupted.
That means patients temporarily have a greater risk of problems such as bacterial infection or herpes simplex reactivation.
Proper aftercare therefore remains extremely important.
The Possible Connection With Immune Surveillance and Sun-Damaged Cells
The most interesting long-term effect may not be a simple increase in immune cells.
Instead, resurfacing may improve the biological environment in which those cells and keratinocytes operate.
By removing some damaged tissue, reducing senescent fibroblasts, increasing IGF-1 signalling and reconstructing the extracellular matrix, fractional resurfacing may help create conditions in which epidermal cells respond more normally to future UV injury.
The IGF-1 research is particularly important here.
Older skin with low fibroblast-derived IGF-1 may allow keratinocytes containing UV-damaged DNA to respond less appropriately.
Fractional resurfacing appears capable, at least in studied populations, of restoring some of this signalling.
This may help explain why some studies have found reductions in actinic keratoses following resurfacing.
But CO2 laser should not currently be described as a replacement for established skin-cancer prevention or surveillance.
Patients still need:
Regular sunscreen
Protective clothing
Appropriate skin examinations
Biopsy of suspicious lesions
Treatment of precancerous lesions when indicated
A Useful Way to Think About the Whole Process
The biology of CO2 laser resurfacing can be simplified into five stages.
1. Controlled Injury
The CO2 laser creates microscopic zones of ablation and heat.
2. Cleanup
Inflammatory cells and matrix metalloproteinases help remove damaged cells and fragmented extracellular matrix.
3. Cellular Stress Response
Heat-shock proteins such as HSP70/HSP72 help cells manage thermal stress, while HSP47 participates in collagen production and organisation.
4. Reconstruction
Fibroblasts become active. TGF-β and other growth signals contribute to new collagen formation, extracellular-matrix remodelling and elastin changes.
5. Longer-Term Reorganisation
New collagen continues developing for months. Fibroblast behaviour and dermal-epidermal signalling may change, including restoration of IGF-1 in aged skin.
This is why CO2 resurfacing can affect much more than pigmentation.
Why Does the Skin Continue Improving for Months?
The peeling that patients see after laser treatment is only the most obvious part of healing.
Underneath the surface, collagen and extracellular-matrix remodelling continue.
Human fractional CO2 studies have demonstrated heat-shock responses and collagen/elastin changes lasting for several months.
The latest evidence synthesis also reports prolonged increases in important collagen proteins following fractional and fully ablative laser resurfacing.
That is why judging the final result only a few weeks after treatment can be misleading.
Skin biology continues changing long after the surface has healed.
So Does CO2 Laser Really “Remove” Sun Damage?
It is better to say that CO2 laser removes some damaged tissue and remodels many of the biological changes caused by photoaging.
It cannot erase every DNA mutation created during decades of sun exposure.
It cannot guarantee that future actinic keratoses or skin cancers will not develop.
And it cannot stop natural aging.
What it can do is trigger a surprisingly sophisticated repair process.
That process includes:
Removal of portions of damaged epidermis
Degradation of fragmented extracellular matrix
Temporary activation of MMPs
Activation of heat-shock proteins
Fibroblast stimulation
TGF-β signalling
Production of new collagen
Remodelling of elastin
Changes in inflammatory signalling
Recruitment of immune cells
Activation of antimicrobial peptides
Reduction of some senescent fibroblasts
Restoration of IGF-1 signalling in some studies
Improved communication between the dermis and epidermis
That is a much better explanation for the results of CO2 laser resurfacing than simply saying the laser “burns off the damaged skin.”
The Bottom Line
Fractional CO2 laser resurfacing works because it uses a controlled injury to activate controlled regeneration.
The laser first creates microscopic areas of damage.
The skin then begins cleaning up old tissue. Matrix metalloproteinases help break down fragmented extracellular matrix. Immune cells clear damaged material. Heat-shock proteins help cells respond to stress.
Fibroblasts then begin rebuilding.
New collagen is produced and reorganised. HSP47 helps with collagen processing. Growth factors such as TGF-β participate in the rebuilding process.
At the same time, there is growing evidence that fractional resurfacing can affect deeper aspects of skin aging, including fibroblast senescence and IGF-1 signalling between the dermis and epidermis.
Research also suggests that ablative resurfacing may improve the biological behaviour of severely sun-damaged skin and reduce actinic keratoses in some older patients.
However, this does not mean CO2 laser should be considered a proven replacement for established skin-cancer prevention or treatment.
The strongest conclusion supported by current evidence is this:
CO2 laser resurfacing does much more than remove the visible surface of sun-damaged skin. It activates a coordinated biological repair response involving extracellular-matrix turnover, heat-shock proteins, fibroblasts, growth factors, collagen formation and local immune signalling.
That combination of removing damaged tissue and stimulating new tissue is what makes fractional CO2 resurfacing such a powerful treatment for photoaged skin.
Key Evidence Behind These Biological Mechanisms
The scientific evidence includes human biopsy studies showing increased MMP-1, MMP-3, MMP-9 and other matrix-remodelling enzymes following fractional CO2 resurfacing of photodamaged skin.
Human histological studies have demonstrated HSP70/HSP72 and HSP47 activation after fractional CO2 treatment, with collagen and elastin remodelling continuing for several months.
Human studies of aged skin have demonstrated that fractional resurfacing can decrease senescent fibroblasts, restore dermal IGF-1 expression and improve the epidermal response to UVB exposure.
A CO2-specific study involving 30 men with scalp actinic keratoses reported increased IGF-1 expression after treatment together with a substantial reduction in actinic keratoses.
A randomized study of 48 older adults found sustained reductions in actinic keratoses and keratinocyte cancers after ablative fractional resurfacing, although that important study used a 2790-nm YSGG fractional laser rather than CO2.
Finally, a 2026 scoping review examining 20 studies concluded that ablative laser treatment produces a coordinated biological response involving inflammation, metalloproteinase activity, extracellular-matrix remodelling, collagen formation, elastogenesis and immune-related signalling.