Biomaterial strategies using hydrogels to prevent or treat adhesions

Hydrogels for Organ Adhesions

Advances in Hydrogel-Based Biomaterials for Preventing and Treating Postoperative Adhesions: A New Horizon

Postoperative adhesions remain one of the most persistent and challenging complications in surgical medicine, affecting millions globally. These fibrous bands can tether organs, cause chronic pain, obstruct intestines, impair fertility, and complicate reoperations, leading to increased morbidity, prolonged hospital stays, and significant economic burdens. Despite extensive research over decades, traditional prevention strategies—mainly physical barrier agents like Seprafilm or Surgicel—have shown limited efficacy, often hampered by short-lived presence, application difficulties, and limited biological activity.

Recent breakthroughs in biomaterials—particularly hydrogels—are now redefining the landscape of adhesion prevention and treatment, offering multifunctional solutions that address both mechanical and biological facets of adhesion formation.

The Clinical Burden and Limitations of Traditional Strategies

Surgical trauma triggers an inflammatory cascade involving cytokine release and cellular activation, notably involving pathways such as NF-κB, which promotes fibrosis and adhesion formation. The consequences include:

Intestinal obstructions, occurring in approximately 2% of laparotomy cases.
Chronic pelvic pain and infertility, especially after gynecological surgeries.
Higher reoperation risks, with increased operative times and complication rates.
Economic impacts, including extended hospital stays, additional procedures, and loss of productivity.

Diagnostic accuracy for adhesions remains poor; standard imaging (MRI, ultrasound) often fails to reliably detect thin or complex adhesions, emphasizing the importance of effective prevention.

Limitations of Traditional Barrier Agents

Historically, surgeons have relied on physical barriers such as Seprafilm or Surgicel to prevent adhesions. However, these agents have notable limitations:

Transient presence: Often resorb before tissue healing completes.
Limited biological modulation: They serve mainly as mechanical separators, offering little to no modulation of inflammation or fibrosis.
Application challenges: Difficult to deploy effectively during minimally invasive procedures or in complex anatomical regions.
Lack of active biological functions: Do not deliver therapeutic agents or promote tissue regeneration.

Pharmacological approaches, including systemic anti-inflammatory drugs, have shown limited clinical success, often due to systemic side effects and poor localization at the surgical site.

The Rise of Hydrogel Biomaterials: A Multifaceted Innovation

Hydrogels, with their hydrophilic polymer networks capable of absorbing substantial water content, are now at the forefront of adhesion prevention strategies. Recent advances have highlighted several advantageous features:

Mechanical Tunability and Conformal Application

Tunable degradation: Hydrogels can be engineered to degrade over specific timelines aligned with tissue healing.
Conformity: Their soft, moldable nature allows them to adapt seamlessly to irregular tissue surfaces, ensuring comprehensive coverage.

Injectable, Thermosensitive, and Sprayable Formats

Injectable hydrogels: Delivered minimally invasively, gelling in situ.
Thermosensitive hydrogels: Gel upon reaching body temperature, simplifying application.
Sprayable hydrogels: Facilitating rapid, uniform application during surgery—especially valuable in laparoscopic or minimally invasive procedures.

Drug and Cell Delivery Capabilities

Hydrogels can encapsulate:

Anti-inflammatory agents: To mitigate local inflammatory responses.
Antifibrotic agents: To inhibit excessive scar tissue formation.
Growth factors and stem cells (notably mesenchymal stem cells, MSCs): To promote tissue regeneration and repair.

This dual functionality—serving as a physical barrier and delivering biological modulators—provides a comprehensive approach to preventing adhesions.

Stimuli-Responsive and Smart Designs

Innovative “smart” hydrogels respond to environmental cues such as pH, enzymatic activity, or temperature, enabling on-demand therapeutic release. Such systems aim to maximize efficacy while minimizing systemic exposure.

Recent Evidence: Efficacy and Clinical Potential

Preclinical studies have demonstrated the promising efficacy of hydrogel-based systems:

Biodegradable, thermosensitive sprayable hydrogels have effectively reduced adhesion severity in animal models, confirmed through histology showing diminished fibrous tethering.
Hydrogels loaded with anti-inflammatory drugs outperform traditional barriers in reducing fibrosis.
Incorporation of growth factors and MSCs enhances tissue regeneration, with applications including gynecological procedures such as intrauterine adhesion (IUA) treatment.

Clinical Validation and Emerging Data

Early-phase clinical trials are encouraging:

Patients treated with hydrogel barriers experienced fewer adhesions and lower reoperation rates.
The LASSO trial (Laparoscopic vs. Open Adhesiolysis for Adhesive Small Bowel Obstruction), published in JAMA Surgery, highlights the potential of innovative adhesion prevention strategies—including hydrogels—to reduce postoperative complications.
Bioactive hydrogels loaded with MSCs are showing remarkable potential in endometrial regeneration, offering hope for women suffering from IUA and related infertility issues.

Furthermore, a recent comprehensive review titled "Recent Trends in the Application of Polymer-Based Biomaterials in..." underscores the importance of multifunctionality—combining mechanical protection, biological activity, and stimuli-responsiveness—in modern biomaterial design. It also emphasizes that translational challenges—such as ensuring safety, reproducibility, and regulatory approval—must be addressed to facilitate widespread clinical adoption.

Mechanistic Insights: Targeting Inflammation and Fibrosis

Understanding the biological pathways involved in adhesion formation has informed hydrogel design. The NF-κB pathway plays a central role in mediating inflammation and fibrosis in peritoneal tissues:

NF-κB activation promotes cytokine release, cellular infiltration, and fibrotic tissue deposition.
Hydrogel strategies that incorporate NF-κB inhibitors or modulate upstream inflammatory signals have shown promise in reducing adhesion severity.
Incorporating anti-inflammatory agents directly into hydrogels enables localized, sustained suppression of deleterious pathways, preventing excessive fibrosis.

Remaining Challenges and Future Directions

Despite promising advances, several hurdles remain:

Regulatory approval: Needs comprehensive safety, efficacy, and long-term safety data.
Manufacturing scalability: Producing consistent, cost-effective hydrogels suitable for clinical use.
Long-term safety: Monitoring immune responses, degradation products, and potential toxicity.
Cost-effectiveness: Demonstrating economic benefits over existing strategies.
Personalization: Developing patient-specific solutions, possibly leveraging 3D printing and nanotechnology.

Future research is focusing on multifunctional, stimuli-responsive hydrogels loaded with bioactive agents and stem cells, designed to respond dynamically to the healing environment, thereby maximizing therapeutic benefits and minimizing complications.

Current Status and Clinical Implications

Hydrogels are rapidly transitioning from experimental platforms to clinical tools. Their mechanical flexibility, biological activity, and technological versatility position them as promising candidates to revolutionize adhesion prevention. The integration of sprayable, bioactive, and stem cell–loaded hydrogels is particularly promising for minimally invasive surgeries.

Implications include:

Reduced reoperation rates, decreasing patient morbidity.
Lower healthcare costs due to fewer postoperative complications.
Enhanced patient outcomes and quality of life through improved tissue healing and reduced pain.

Conclusion

Recent innovations in hydrogel biomaterials—especially those that are stimuli-responsive, bioactive, and capable of delivering regenerative cells—are opening a new frontier in postoperative adhesion management. Their ability to combine physical separation with targeted biological modulation makes them a comprehensive solution to a longstanding surgical challenge. As ongoing clinical trials and technological advancements continue, these hydrogels are poised to become standard tools in surgical practice, transforming patient care and outcomes.

In summary, the evolving landscape of hydrogel-based biomaterials offers a promising, multifunctional approach to reducing postoperative adhesions. Continued research, regulatory progress, and technological integration will be critical to translating these innovations from bench to bedside on a broad scale.

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Updated Feb 26, 2026

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