Peptide Therapy for Post-Surgical Adhesions

Adhesions form after roughly 93% of abdominal and pelvic surgeries. They are bands of scar tissue that bind organs and tissues together where they should not be connected. Most are clinically silent. But when they are not silent, the consequences can be severe: chronic abdominal pain, bowel obstruction, infertility, and repeat surgeries that often create more adhesions.

Despite billions spent on research and dozens of commercial anti-adhesion products, no currently available method provides fully satisfactory prevention. Barrier films reduce adhesions by single-digit percentages. Surgical technique helps but does not solve the problem. And once adhesions form, the only treatment is surgery — which, ironically, predisposes patients to more adhesions.

This is the situation into which peptide therapy is entering. A small but growing body of research suggests that peptides targeting inflammation, fibrosis, and tissue remodeling could address adhesion formation at its biological roots rather than simply placing a physical barrier between tissues. The evidence is early. But for a problem this common and this poorly solved, the research is worth following.

What Are Post-Surgical Adhesions?
How Adhesions Form: The Biology
Current Prevention and Treatment Options
Peptides Under Investigation
Comparing the Evidence
Limitations of Current Research
Clinical Outlook
Frequently Asked Questions
The Bottom Line
References

What Are Post-Surgical Adhesions?

Adhesions are pathological bands of fibrous tissue that form between surfaces inside body cavities. They range from thin films of connective tissue to thick, vascularized bridges containing blood vessels and nerve tissue. They can form between loops of intestine, between organs and the abdominal wall, around the fallopian tubes, or in any space where surgical trauma has occurred.

The numbers are striking:

Adhesions develop after up to 95% of all operations, regardless of procedure or body location (PMC, 2021).
They are the primary cause of small bowel obstruction, accounting for approximately 70% of bowel obstruction admissions.
In gynecological surgery, adhesions are a leading cause of secondary infertility and chronic pelvic pain.
In the United States, adhesion-related complications drive an estimated 300,000+ hospitalizations annually, with healthcare costs exceeding $1.3 billion per year.
About 35% of patients who undergo open abdominal or pelvic surgery are readmitted within 10 years for conditions related to or potentially caused by adhesions.

The majority of adhesions are clinically silent — patients never know they have them. But when symptoms do occur, the consequences can be lifelong: recurrent intestinal obstruction requiring multiple hospitalizations, chronic pain that does not respond to standard analgesics, and infertility requiring assisted reproduction.

How Adhesions Form: The Biology

Understanding why adhesions form is essential to understanding why peptides might help prevent them. The process starts with surgical trauma and unfolds through a cascade of inflammatory, coagulation, and fibrotic events.

Step 1: Tissue injury and inflammation. Surgical incision, cautery, tissue handling, and drying of peritoneal surfaces all trigger an immediate inflammatory response. Damaged cells release pro-inflammatory cytokines — particularly TNF-alpha, IL-6, and IL-1 — which recruit neutrophils, macrophages, and mast cells to the injury site. Mast cells, found in high concentrations at adhesion sites, release histamine, serotonin, and chymase. Chymase activates TGF-beta, a master regulator of fibrosis (PMC, 2021).

Step 2: Fibrin deposition. Within hours, the coagulation cascade produces a fibrin matrix over injured surfaces. This fibrin acts as a temporary scaffold — the body's way of sealing the wound. In normal healing, fibrinolytic enzymes (particularly tissue plasminogen activator, or tPA) break down this fibrin within 72 hours, and the surfaces heal separately.

Step 3: Failed fibrinolysis. This is where adhesions diverge from normal healing. Surgical trauma suppresses tPA activity while increasing plasminogen activator inhibitor (PAI-1). The result: fibrin persists. Instead of dissolving, the temporary fibrin scaffold becomes colonized by fibroblasts.

Step 4: Fibrosis and permanent adhesion. Fibroblasts invade the persistent fibrin matrix and begin depositing collagen, creating a permanent fibrous bridge. Blood vessels grow into this bridge (angiogenesis), nerve fibers follow, and the adhesion becomes a living, sometimes pain-generating tissue. TGF-beta drives myofibroblast differentiation — the cells primarily responsible for wound contraction and fibrotic scar formation.

Step 5: Tissue hypoxia compounds the problem. Surgical trauma creates local oxygen deprivation, which increases expression of vascular endothelial growth factor (VEGF) and further promotes the disorganized tissue growth that characterizes adhesions.

A 2025 study published in Frontiers in Immunology highlighted the central role of peritoneal macrophages in this process. These macrophages recognize sterile injury, initiate repair, form aggregates, and regulate coagulation, inflammation, fibrosis, and fibrinolysis. Targeting macrophage behavior is now considered one of the most promising strategies for adhesion prevention (Frontiers, 2025).

Current Prevention and Treatment Options

The existing toolkit for adhesion prevention is limited:

Physical barrier agents. The most established approach places a physical barrier between injured surfaces during surgery. FDA-approved products include Seprafilm (hyaluronate carboxymethylcellulose), Interceed (oxidized regenerated cellulose), and various hydrogel-based barriers. However, clinical trial data shows these barriers reduce adhesions by only 2–8% in practice. They are difficult to apply in laparoscopic surgery, do not address the underlying biology, and can only be placed where the surgeon predicts adhesions will form.

Minimally invasive surgery. Laparoscopic techniques create less tissue trauma and peritoneal drying than open surgery, and are the only approach consistently shown to reduce adhesion formation. But they do not eliminate adhesions — they just reduce them.

Anti-inflammatory agents. Steroids, NSAIDs, and other anti-inflammatory drugs have been tested with inconsistent results. IL-6 receptor antibodies have shown promise in preclinical models.

Fibrinolytic agents. Direct application of tPA to surgical sites has been studied but raises concerns about bleeding complications.

Surgical adhesiolysis. Once formed, the only treatment for symptomatic adhesions is surgery to cut them apart. This unfortunately creates new tissue trauma and new adhesions. Roughly 20% of patients require repeat adhesiolysis within five years.

This is why researchers are looking for approaches that address the biological cascade — inflammation, failed fibrinolysis, and fibrosis — rather than simply placing a physical barrier. Peptides that modulate these pathways are among the most active areas of investigation.

Peptides Under Investigation

BPC-157: Anti-Inflammatory and Anti-Fibrotic Mechanisms

What it is: BPC-157 (Body Protection Compound-157) is a 15-amino-acid peptide derived from a protective protein in human gastric juice. It is the most extensively studied peptide for tissue repair, with over 100 published preclinical studies spanning three decades.

Why it matters for adhesions: BPC-157 targets several key steps in the adhesion formation cascade:

Anti-inflammatory action. BPC-157 significantly reduces pro-inflammatory cytokines TNF-alpha, IL-6, and IFN-gamma — the same cytokines that drive the early inflammatory phase of adhesion formation. It promotes macrophage polarization from the pro-inflammatory M1 phenotype toward the reparative M2 phenotype, which reduces fibrosis and supports organized tissue regeneration rather than disorganized scar formation (PMC, 2025).

Anti-fibrotic effects. By modulating inflammatory pathways and reducing excessive fibrosis, BPC-157 could theoretically limit the collagen overgrowth that transforms temporary fibrin scaffolds into permanent adhesions.

Angiogenesis regulation. BPC-157 upregulates VEGF and stimulates organized blood vessel formation. This is a double-edged sword in adhesion biology — angiogenesis is part of how adhesions become permanent, but controlled angiogenesis is also essential for normal wound healing. The key may be that BPC-157 promotes organized tissue repair rather than the disorganized fibrotic response that creates adhesions.

Post-surgical healing evidence. A rat study on quadriceps muscle-to-bone detachment showed that oral BPC-157 therapy (10 mcg/kg/day) provided consistent healing across macro/microscopic, ultrasonic, MRI, biomechanical, and functional assessments over 90 days, while control animals showed healing failure (PMC, 2025).

Tissue repair pathways. BPC-157 activates the FAK-paxillin pathway (important for cell migration to wound sites), upregulates growth hormone receptor expression in tissue fibroblasts, and stimulates the EGR-1 gene that controls growth factor production.

Evidence quality for adhesions: No direct published research on BPC-157 for adhesion prevention exists. The rationale is built on its demonstrated anti-inflammatory, anti-fibrotic, and tissue-remodeling properties in other surgical contexts. The theoretical fit is strong, but direct evidence is missing.

Regulatory status: Not FDA-approved. Classified as a Category 2 bulk drug substance by the FDA in 2023, restricting commercial compounding. For a comprehensive review of its legal status, see our BPC-157 legal status guide.

PXL01: The Clinical Frontrunner

What it is: PXL01 is a synthetic peptide derived from human lactoferrin, the antimicrobial protein found in breast milk. It was developed specifically for adhesion prevention — making it unique among the peptides on this list.

Why it matters for adhesions: PXL01 has the most direct clinical evidence of any peptide for adhesion prevention. In vitro studies show it reduces secretion of inflammatory cytokines, promotes fibrinolysis (the process that breaks down the fibrin matrix before adhesions form), and reduces infection — hitting three of the key mechanisms in adhesion biology.

The clinical data:

PXL01 is formulated with sodium hyaluronate (HA) as a carrier that provides controlled release of the peptide at the surgical site. Clinical testing has focused on flexor tendon repair in the hand, where adhesions are a major problem that restricts finger mobility after surgery.

Preclinical results: In a rabbit flexor tendon model, a single application of PXL01 in HA significantly improved joint mobility compared to HA alone, without negative effects on tendon healing strength. PXL01 at 20 mg/mL was the lowest effective concentration (Wiig et al., 2011).
Phase II RCT: A multi-centre, randomized, parallel-group study evaluated PXL01 versus placebo in patients admitted for flexor tendon repair surgery in zones I or II of the hand. Six- and twelve-month follow-up data showed statistically significant improvement in functional hand recovery compared to placebo. Treatment with PXL01 in HA increased digit mobility without increasing tendon rupture rates or causing tissue damage (PMC, 2014).
Mechanism insight: A subsequent study showed PXL01 in sodium hyaluronate increases PRG4 expression — a potential mechanism for its anti-adhesion effects. PRG4 (lubricin) is a glycoprotein that reduces tissue surface friction, which may help prevent the physical contact between healing surfaces that initiates adhesion formation (PMC, 2017).
New applications (2025): Recent research has expanded PXL01's scope to nerve regeneration. A 2025 study in Frontiers in Cell and Developmental Biology showed the lactoferrin-derived peptide improved axonal outgrowth in injured peripheral nerves, suggesting broader applications in post-surgical recovery (Frontiers, 2025).

Evidence quality: This is the strongest clinical evidence for any peptide in adhesion prevention — a Phase II randomized controlled trial with positive results. The limitation is that the data is from hand surgery specifically, and generalization to abdominal or pelvic adhesions has not been clinically tested.

Status: PXL01 is not yet commercially available. Clinical development has been limited by the resources of its parent company, Pergamum (now part of Pharmanest).

TB-500 (Thymosin Beta-4): Reducing Fibrosis at the Source

What it is: Thymosin beta-4 (Tb4) is a 43-amino-acid peptide found in nearly all human cells. TB-500 is a synthetic version of an active region of Tb4. It is produced by the TMSB4X gene and is abundant in platelets, macrophages, and epithelial tissues.

Why it matters for adhesions: TB-500's anti-fibrotic properties directly target the mechanism that converts temporary fibrin scaffolds into permanent adhesions.

Anti-fibrotic mechanisms:

TB-500 decreases the number of myofibroblasts in healing wounds — the cells primarily responsible for wound contraction and fibrotic scar formation. This reduction correlates with decreased scar formation and reduced tissue fibrosis.
It modulates TGF-beta signaling, the master pathway driving fibrosis. In liver fibrosis models, TB-500 downregulated TGF-beta receptor II, blunting the fibrogenic signaling cascade in both hepatic stellate cells and hepatocytes.
It reduces collagen and fibronectin discharge while decreasing macrophage migration to damaged sites.
TB-500 inhibits NF-kB signaling, specifically blocking nuclear translocation of RelA/p65, which prevents transcriptional activation of pro-inflammatory genes. This creates a less inflammatory environment that favors organized healing over fibrotic scarring.

Broader tissue repair evidence: The peptide's anti-fibrotic effects have been documented across multiple organ systems. In renal fibrosis models, it alleviated fibrosis and tubular cell death through TGF-beta pathway inhibition. In pulmonary fibrosis, it showed protective effects with notable inflammation reduction. In cardiac tissue, it promoted organized remodeling with reduced fibrosis, helping maintain ventricular function. Compare its healing profile with BPC-157 in our TB-500 vs. BPC-157 comparison.

Evidence quality for adhesions: No published clinical trials for adhesion prevention. The anti-fibrotic mechanism is well established in preclinical models across multiple tissues. Phase I safety trials showed no toxicities or serious adverse events at doses from 42 to 1,260 mg over 14 days. The gap between preclinical promise and clinical proof remains wide.

Regulatory status: Not FDA-approved for human therapeutic use. Banned by WADA for competitive sports.

GHK-Cu: Remodeling Collagen, Reducing Scars

What it is: GHK-Cu (glycyl-L-histidyl-L-lysine copper complex) is a naturally occurring tripeptide present in human plasma. First isolated in 1973, it has a strong affinity for copper and a broad range of effects on tissue repair, inflammation, and gene expression.

Why it matters for adhesions: GHK-Cu's unique value for adhesion prevention lies in its ability to promote balanced collagen remodeling rather than excessive fibrosis:

It stimulates both collagen synthesis and breakdown, along with glycosaminoglycans, and modulates the activity of metalloproteinases and their inhibitors. This balanced remodeling is exactly what distinguishes normal healing from adhesion formation.
GHK-Cu reduces fibrosis in liver, lung, and skin models by downregulating TGF-beta-1 and other pro-fibrotic genes.
It reduces TNF-alpha-induced secretion of IL-6 in fibroblasts, dampening the inflammatory cascade that triggers fibrosis.
Large-scale gene studies show GHK-Cu influences hundreds of genes, tending to upregulate those involved in regeneration and downregulate those associated with inflammation or fibrosis (PMC, 2018).

Wound healing track record: Research shows GHK-Cu accelerates wound closure by 40–50% compared to controls. Clinical studies have demonstrated efficacy in diabetic ulcers and post-Mohs surgery healing. In animal models, collagen dressings incorporating GHK-Cu accelerated healing with increased collagen synthesis and fibroblast activation. GHK-Cu also improved healing of ischemic wounds, reducing metalloproteinases 2 and 9 and TNF-beta concentrations (PMC, 2015).

Limitations: GHK-Cu is sensitive to breakdown by carboxypeptidase enzymes, particularly in wound fluid. This enzymatic instability limits how long the peptide remains active at surgical sites. Researchers are addressing this with novel delivery systems including hydrogels and electrospun dressings that provide sustained release. Explore more about copper peptide wound healing research in our GHK-Cu wound healing evidence review.

Evidence quality for adhesions: No direct evidence for adhesion prevention. Strong preclinical base for balanced collagen remodeling and anti-fibrotic activity. Clinical wound healing data exists but is limited. Injectable forms were prohibited for commercial compounding by the FDA in 2023.

Comparing the Evidence

Peptide	Direct Adhesion Data	Human Clinical Trials	Anti-Fibrotic Evidence	Anti-Inflammatory Evidence	Clinical Availability
BPC-157	None	Phase I/II (IBD)	Moderate (preclinical)	Strong (preclinical)	Limited (FDA Category 2)
PXL01	Phase II RCT (hand surgery)	Yes — positive results	Moderate	Moderate	Not commercially available
TB-500	None	Phase I safety only	Strong (multi-organ)	Strong	Limited (not FDA-approved)
GHK-Cu	None	Limited (wound healing)	Moderate-Strong	Moderate	Limited (FDA restricted)

PXL01 leads the field with the only human clinical trial data specific to adhesion prevention. The other peptides have strong mechanistic rationale but lack the direct clinical evidence needed to establish them as adhesion treatments.

Limitations of Current Research

Being clear about what we do not know is as important as summarizing what we do know:

No large-scale human trials for most peptides. Apart from PXL01's Phase II trial, the evidence base for peptide-based adhesion prevention is entirely preclinical. Animal models of adhesion formation do not perfectly replicate human surgical conditions.

Adhesion biology is complex. Three core processes — failed fibrinolysis, inflammation, and hypoxia — interact in ways that are not fully understood. A 2025 review from the American College of Surgeons noted that the multifactorial nature of adhesion formation has resulted in therapeutic options that consistently fail to demonstrate safety and efficacy at scale (ACS, 2025).

Timing matters. Adhesion formation is a dynamic process that unfolds over days to weeks. A peptide that reduces inflammation during the first 48 hours may have very different effects if administered later. Optimal dosing windows have not been established.

Delivery challenges. Most peptides have short half-lives. BPC-157's half-life is under 30 minutes; GHK-Cu is rapidly degraded by wound fluid enzymes. Getting adequate peptide concentrations to the right tissues at the right time remains a practical challenge.

Regulatory barriers. Several of the most promising peptides (BPC-157, GHK-Cu) face FDA restrictions on compounding, limiting access even for clinical research.

Clinical Outlook

The adhesion prevention field is at an inflection point. After decades of modest results from physical barriers, the research community is shifting toward biological approaches — targeting the inflammatory, fibrotic, and fibrinolytic pathways that actually create adhesions.

Several developments are converging:

Macrophage-targeted therapies are gaining traction. The 2025 research identifying peritoneal macrophages as central regulators of adhesion formation opens new therapeutic targets that peptides are well suited to address.

Self-assembling peptide hydrogels like RADA16 are already FDA-cleared for surgical hemostasis and, notably, adhesion prevention after nasal surgery. These represent the first peptide-based materials to gain regulatory approval in this space.

Nanoparticle delivery systems — including PLGA nanoparticles that can deliver TGF-beta-targeting gene therapy to surgical sites — are being combined with peptide approaches to overcome the half-life and delivery challenges.

Gene therapy integration. Polylactic-co-glycolic acid nanoparticles have been used to deliver TGF-beta-1 miRNA plasmids, potentially downregulating the master fibrosis pathway. Combining this approach with anti-fibrotic peptides could produce additive effects.

The most realistic near-term scenario is not a single peptide cure for adhesions, but rather multimodal approaches that combine physical barriers, anti-fibrotic peptides, anti-inflammatory agents, and novel delivery systems — applied at the time of surgery to shift the healing response away from fibrosis and toward organized tissue repair.

For patients currently dealing with post-surgical adhesions or facing surgery with adhesion risk, the best present-day strategies remain minimally invasive surgical techniques, careful tissue handling, and the judicious use of available barrier products — combined with working with surgeons who take adhesion prevention seriously. Peptide therapy is not yet part of standard care for adhesions, but the direction of research suggests it will be within the next decade.

Frequently Asked Questions

Can peptides dissolve existing adhesions? No current evidence supports the use of peptides to break down established adhesions. Once adhesions have matured into vascularized, collagen-rich tissue, they require surgical adhesiolysis to remove. The promise of peptide therapy lies primarily in prevention — intervening during the critical window when adhesions are forming rather than trying to reverse established fibrous bands.

Has BPC-157 been tested specifically for adhesion prevention? Not directly. No published study has tested BPC-157 in an adhesion prevention model. The rationale for its potential use comes from its demonstrated anti-inflammatory, anti-fibrotic, and tissue-remodeling properties in other surgical healing contexts. For more on BPC-157's broader effects on surgical recovery, see our guide on best peptides for post-surgery recovery.

What about using peptides alongside existing anti-adhesion barriers? This combination approach is theoretically appealing — a physical barrier to separate surfaces plus a biological agent to reduce the inflammatory and fibrotic response. Self-assembling peptide hydrogels like RADA16 already combine both functions in a single material. For conventional peptides combined with barrier films, no clinical data exists yet.

Are any peptide-based adhesion prevention products FDA-approved? The RADA16-based self-assembling peptide hydrogel (marketed as AC5/PuraBond) received FDA clearance in 2019 as an intraoperative hemostatic wound dressing that also functions to prevent adhesion formation after nasal surgery. It is the first and currently only peptide-based material with FDA clearance specifically mentioning adhesion prevention.

How would a patient access peptide therapy for adhesion prevention? Currently, most of these peptides are not available through standard surgical practice. PXL01 is not commercially available. BPC-157 and GHK-Cu face FDA compounding restrictions. TB-500 is available through some compounding pharmacies but is not approved for this use. Patients interested in peptide approaches should discuss options with their surgeon and a physician experienced in peptide therapy well in advance of scheduled surgery. See our guides on how to choose a peptide therapy clinic and finding a compounding pharmacy.

The Bottom Line

Post-surgical adhesions remain one of the most common and poorly solved complications in modern surgery. Current prevention strategies — physical barriers and minimally invasive technique — provide incomplete protection. Peptide therapy offers a biologically rational alternative: targeting the inflammation, failed fibrinolysis, and fibrosis that actually create adhesions.

PXL01 has the strongest clinical evidence, with a positive Phase II trial in hand surgery. BPC-157 and TB-500 bring strong anti-fibrotic preclinical data. GHK-Cu offers unique collagen-remodeling properties. Self-assembling peptide hydrogels are already FDA-cleared for related surgical applications.

But the honest assessment is that we are still in the early innings. Large-scale human trials specifically powered to test peptide-based adhesion prevention in abdominal and pelvic surgery have not been conducted. The path from "biologically plausible" to "standard of care" requires years of clinical development.

For now, the research justifies cautious optimism and continued attention — especially for patients and surgeons already thinking about adhesion risk in upcoming procedures.

References

Brüggmann, D., et al. (2021). Post-operative adhesions: A comprehensive review of mechanisms. Biomolecules, 11(8), 1027. PMC
Koninckx, P. R., et al. (2021). Prevention of post-operative adhesions: A comprehensive review of present and emerging strategies. Biomolecules, 11(7), 1027. PMC
ACS Surgical Adhesions Improvement Project (2025). Surgical adhesions improvement project advances disease science. ACS Bulletin, 110(6). ACS
Wang, Y., et al. (2025). Postoperative adhesion formation: the role of peritoneal macrophages and targeting therapy. Frontiers in Immunology, 16. Frontiers
Wiig, M., et al. (2011). A lactoferrin-derived peptide (PXL01) for the reduction of adhesion formation in flexor tendon surgery. Journal of Hand Surgery (European Volume), 36(8), 656–662. PubMed
Wiig, M., et al. (2014). PXL01 in sodium hyaluronate for improvement of hand recovery after flexor tendon repair surgery: randomized controlled trial. PLoS ONE, 9(10), e110735. PMC
Sheldon, H., et al. (2017). PXL01 in sodium hyaluronate results in increased PRG4 expression. Upsala Journal of Medical Sciences, 122(1), 28–34. PMC
Pickart, L., & Margolina, A. (2018). Regenerative and protective actions of the GHK-Cu peptide in the light of the new gene data. International Journal of Molecular Sciences, 19(7), 1987. PMC
Seiwerth, S., et al. (2021). Stable gastric pentadecapeptide BPC 157 and wound healing. Current Pharmaceutical Design, 24(18), 1991–2001. PMC
Delta Peptides (2025). TB-500 (Thymosin Beta-4) Clinical Profile. Delta Peptides

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