Anti-adhesion Barrier Research Articles

Micro- and nano-environment dual-modulated anti-tendon adhesion barrier membranes

Despite promise in preventing peritendinous adhesion, electrospun membranes face many challenges related to their complex fabrication process, untargeted/uncontrolled drug delivery and consequently low therapeutical effect. Here, a micro-and nano-environment dual-modulated barrier membrane (MNBM) with on-demand gene delivery capability is presented. Our MNBM is developed by first preparing extracellular signal-regulated kinase-2 (ERK2) siRNA-loaded gelatin methacryloyl (GelMA) nanogels via facile nano-emulsification technique, then incorporating these nanogels into poly-L-lactic acid (PLLA) fibers via simple blending electrospinning. The GelMA nanogels offer a nano-niche for ERK2-siRNA encapsulation and allow for a nano-environment controlled siRNA release by readily tuning the GelMA concentrations during nano-emulsification, while the resultant MNBM can mediate a micro-environment controlled siRNA delivery in response to the matrix metalloproteinase-2 (MMP-2) enriched micro-environment at the tendon repair site. Such MNBM can not only biologically orchestrate fibroblast behaviors by silencing the target gene expression, but also physically shield the tendon from extrinsic cell/tissue invasion. This study provides a proof-of-concept of anti-adhesion barrier membrane as an intelligent gene delivery system to offer a spatiotemporal and biophysical dual control over tendon recovery according to disease state and ensure long-term therapeutic efficacy. We envision such MNBM represents a promising therapeutic platform with great efficacy to achieve adhesion-free tendon repair.

Hotmelt tissue adhesive with supramolecularly-controlled sol-gel transition for preventing postoperative abdominal adhesion

Postoperative adhesion is a serious and frequent complication, but there is currently no reliable anti-adhesive barrier available due to low tissue adhesiveness, undesirable chemical reactions, and poor operability. To overcome these problems, we report a single-syringe hotmelt tissue adhesive that dissolves upon warming over 40 °C and coheres at 37 °C as a postoperative barrier. Tendon-derived gelatin was conjugated with the ureidopyrimidinone unit to supramolecularly control the sol-gel transition behavior. This functionalization improved bulk mechanical strength, tissue-adhesive properties, and stability under physiological conditions through the augmentation of intermolecular hydrogen bonding by ureidopyrimidinone unit. This biocompatible adhesive prevented postoperative adhesion between cecum and abdominal wall in adhesion models of rats. This hotmelt tissue adhesive has enormous potential to prevent postoperative complications and may contribute to minimally invasive surgery. Statement of significanceThere is a strong need to develop medical tissue adhesives with high biocompatibility, tissue adhesiveness, and operatability to prevent postoperative complications. In this report, single syringe, hotmelt-type tissue adhesive was developed by controlling sol-gel transition behavior of gelatin through supramolecular approach. The functionalization of gelatin with quadruple hydrogen bonding improved key features necessary for anti-adhesive barrier including bulk mechanical strength, tissue adhesive property, stability under physiological conditions, and anti-adhesive property. The hotmelt tissue adhesive can be used for a sealant, hemostatic reagent, and wound dressing to prevent postoperative complications including delayed bleeding, perforation, and inflammation and contribute to minimally invasive surgery.

A novel thermosensitive poloxamer-hyaluronic acid- kappa-carrageenan-based hydrogel anti-adhesive agent loaded with 5-fluorouracil: A preclinical study in Sprague-Dawley rats

Although the first-choice treatment for colorectal cancer is cytoreductive surgery combined with chemotherapy, post-surgical peritoneal adhesion and extant malignancy can cause fatal complications. Studies examining hydrogel-based postoperative anti-adhesion treatments are still limited. In this study, several formulations of 5-fluorouracil (5-FU) loaded into hyaluronic acid (HA) and kappa-carrageenan (kCGN)-poloxamer 407 (P407)-based cross-linked hydrogels were prepared and evaluated in vitro and in vivo for their efficacy in preventing adhesion. These hydrogels met a set of desired specifications such as thermosensitive behavior, strong elasticity at body temperature (tan δ < 1.0 at 37 °C), and ability to encapsulate hydrophilic drug and deliver it in a sustained released manner. Our secondary purpose is to provide in situ 5-FU for additional local antitumor effect when the anti-adhesion agent is spread over the tumor site. Over 60% of the total loaded drug was released within 4 h, and about 80% of 5-FU was released after three days. Both the Higuchi and Korsmeyer-Peppas models showed that the mechanism of sustained drug release involved diffusion. The constructed hydrogels were evaluated for in vivo intra-abdominal anti-adhesion barrier efficiency; the HA/kCGN 1%/3% w/v hydrogel formulation showed the best anti-adhesion effect in this preclinical study using Sprague-Dawley rat models.

An enzyme cross-linked hydrogel as a minimally invasive arterial tissue sealing and anti-adhesion barrier

Uncontrollable bleeding is the main cause of death during surgical trauma and accidental injuries. To halt the bleeding caused by arterial rupture is still challenging due to the high pressure and velocity of arterial blood flow. Enzyme-responsive hydrogels have emerged as promising solutions for hemostasis after arterial rupture, largely due to their high hemostatic efficiency and specificity. However, the existing enzyme-responsive hydrogels suffer from weak cross-linking. Here, we report the design of a hemostatic material with nanoporous, combining a transglutaminase enzyme reaction and Schiff base reaction, for percutaneous injection. Here, we show that the resulting burst pressure of the hemostatic material was 134 ± 10 mmHg, which is significantly greater than the normal systolic blood pressure. Most importantly, the material was able to efficiently stop the bleeding a pig and rat arterial vessel models, with a ~10 s gelling time and without the need for the hemostatic clamps on both ends of the vessel injury. Furthermore, the hemostatic material functioned as an anti-adhesion barrier in a rat liver model. The present study describes an effective, injectable hydrogel solution for the rapid and minimally invasive hemostatic treatment of bleeding diseases in parenchymal organs.

Effects of Icodextrin Solution (Adept®) on Ovarian Cancer Cell Proliferation in an In Vitro Model.

Background and objective: Anti-adhesion barriers are currently used during ovarian cancer surgery to decrease adhesion-related morbidity. Adept® (4% icodextrin) solution, a liquid anti-adhesion material, has been widely used during gynecologic surgeries, though the risk of this barrier for oncologic surgery is controversial. The aim of this study was to determine the effect of Adept® solution on the proliferation of ovarian cancer cells. Materials and methods: We assessed the dose- and time-dependent effects of icodextrin on the growth and proliferation of OVCAR-3 and A2780 human ovarian tumor cell lines in vitro. Cell growth was determined by cell number counting. Expressions of cell cycle-regulation proteins (cyclin D1 and cyclin B1) were determined using Western blot analysis. Results: Adept® did not significantly increase ovarian cancer cell growth when tested at various concentrations (0, 1, 5, 10, 15, and 20%, equal to 0, 0.04, 0.2, 0.4, 0.6 and 0.8% icodextrin) and different time points (1–3 days) compared to control cells. Moreover, the protein levels of cyclin D1 and B1 were not overexpression-elevated in icodextrin-treated ovarian cancer cells, either with an increasing concentration or with an increasing treated time. These results demonstrated that Adept® does not activate the growth or proliferation of ovarian cancer cells in either a dose- or time-dependent manner. Conclusions: This study supports the use of Adept® solution as a safe anti-adhesion barrier for ovarian cancer surgery, though further in vivo studies are necessary.

Bioactive NIR-II Light-Responsive Shape Memory Composite Based on Cuprorivaite Nanosheets for Endometrial Regeneration.

Intrauterine adhesions (IUAs) caused by mechanical damage or infection increase the risk of infertility in women. Although numerous physical barriers such as balloon or hydrogel are developed for the prevention of IUAs, the therapeutic efficacy is barely satisfactory due to limited endometrial healing, which may lead to recurrence. Herein, a second near‐infrared (NIR‐II) light‐responsive shape memory composite based on the combination of cuprorivaite (CaCuSi4O10) nanosheets (CUP NSs) as photothermal conversion agents and polymer poly(d,l‐lactide‐co‐trimethylene carbonate) (PT) as shape memory building blocks is developed. The as‐prepared CUP/PT composite possesses excellent shape memory performance under NIR‐II light, and the improved operational feasibility as an antiadhesion barrier for the treatment of IUAs. Moreover, the released ions (Cu, Si) can stimulate the endometrial regeneration due to the angiogenic bioactivity. This study provides a new strategy to prevent IUA and restore the injured endometrium relied on shape memory composite with enhanced tissues reconstruction ability.

Foreign body reaction mimicking local recurrence from polyactide adhesion barrier film after laparoscopic colorectal cancer surgery: A retrospective cohort study.

Polyactide (PLA) barrier is one of the most commonly used materials to prevent the formation of postoperative adhesion. Even though previous studies supported the anti-adhesion efficacy of PLA barrier, there have been limited reports focusing on the associated foreign body reaction. We sought to investigate the potential complication of PLA barrier placement that could lead to unnecessary intervention.This is a retrospective study of colorectal cancer patients with laparoscopic surgery. Cases with stage IV unresectable disease, poor Eastern Cooperative Oncology Group Performance, death within 3 months after the surgery, and insufficient record were excluded. A total of 296 cases were identified in our study and 220 patients received PLA film placement. We compared the incidence of foreign body reaction between the patients with and without PLA film.Among PLA film group, 16 cases had signs of local recurrence on the follow-up image studies. The subsequent operation found 10 patients had no cancerous lesions but only foreign-body-associated granulomas. The incidence of foreign body reaction mimicking local recurrence on image study was 4.5% with high false positive rate of 62.5% on positron emission tomography scan in patients with PLA film. There were only 2 cases without the antiadhesive barrier developed signs of recurrence during active surveillance. Both cases were later confirmed to have malignant peritoneal seeding.The PLA film was associated with rare foreign body reaction that could interfere the accuracy of follow-up program and result in unnecessary surgical intervention. Hence, we recommend avoiding the use of the PLA barrier.

Development of carboxymethyl cellulose/gelatin hybrid hydrogels via radiation-induced cross-linking as novel anti-adhesion barriers

Adhesion after abdominal and pelvic surgery results in severe clinical outcomes and a negative impact on the quality of life of a patient. Implanting barrier materials is a common strategy for preventing postoperative adhesion, and non-adhesive carboxymethylcellulose (CMC) is a widely used material for such purpose. Herein, we present CMC/gelatin (CMC/G) hybrid hydrogels as novel barrier materials that aim to reduce the foreign body response (FBR) by combining the biocompatibility and biodegradability of gelatin and the non-adhesiveness of CMC and by realizing mechanical matching with the host tissue. The hydrogels were prepared by the simple reagent-free γ-ray irradiation-induced cross-linking of CMC and gelatin. The hydrogel composition was controlled by varying the initial mixing ratio. The gelatin fraction provided enzyme-mediated degradability at a content ≥ 40%, and the degradation rate was controlled by the radiation dose. The compressive moduli of the hydrogels were tuned to be identical to that of target abdominal organs (several tens of kPa) via 10–30 kGy radiation. The hydrogels sufficiently prevented adhesion of 3T3-Swiss fibroblast cells owing to the non-adhesive capability of CMC which surpassed the high cell adhesiveness of gelatin in the hydrogels. On the other hand, the added gelatin significantly improved the viability of the few cells that adhered to the hydrogels. We found that hydrogels composed of 60% CMC and 40% gelatin exhibited significantly higher cell viabilities while maintaining the non-adhesiveness which is desirable as barrier materials. The in vitro assessments demonstrated the potential of the hydrogel as a novel barrier material with excellent biocompatibility, wound healing promoting effect, and FBR reducing effect by realizing mechanical matching with the host abdominal organs, especially when it was composed of 60% CMC and 40% gelatin and cross-linked at 10–30 kGy to impart compressive modulus of 20–100 kPa.

Prevention of postoperative adhesions after flexor tendon repair with acellular dermal matrix in Zones III, IV, and V of the hand: A randomized controlled (CONSORT-compliant) trial.

Background:Various techniques have been attempted for preventing postoperative flexor tendon adhesion, such as modification of suture technique, pharmacological agents, and mechanical barriers. However, there is no evidence of the efficacy of these methods in clinical settings. In this study, we present the long-term outcomes of a randomized prospective study in which acellular dermal matrix (ADM) was used to prevent postoperative adhesions after tendon injury in the hand.Methods:From January 2017 to January 2020, all patients with an acute single flexor tendon injury in hand Zones III, IV, or V were candidates. A single-digit, total tendon rupture repaired within 48 hours, from the index finger to the little finger, was included in the study. Patients were randomly allocated to either a control or ADM group. Complications and the range of movements were recorded. Functional outcomes and a patient satisfaction questionnaire were evaluated after 12 months following the tendon repair surgery. The present study is adhered to the CONSORT guidelines.Results:A total of 25 patients was enrolled in the study: 13 patients in the ADM group and 12 in the control group. According to Buck-Gramcko II criteria, the postoperative functional outcome score was 14.38 ± 1.71 in the ADM group and 13.08 ± 1.82 in the control group (P value = .0485). Patient satisfaction was recorded at 8.38 ± 1.44 in the ADM group and 7.08 ± 1.58 in the control group (P value = .0309), a significant difference. There were no differences in complications between the 2 groups.Conclusion:The beneficial effects of ADM after tendon repair were confirmed by improved postoperative functional outcome at flexor Zones III, IV, and V, preventing peritendinous adhesions and acting effectively as an anti-adhesive barrier.

Impact of Perihepatic Adhesions on Liver Regeneration during Two-Stage Hepatectomy for Unresectable Colorectal Liver Metastases: Results from the Sepra-C2T Prospective Trial

Introduction: Two-stage hepatectomy (TSH) is an effective treatment for unresectable colorectal liver metastasis (CLM). Insufficient hepatic growth may prevent from performing the second stage. Peri-hepatic adhesions are frequent after the first hepatectomy. Incidence and severity of adhesions can be prevented by anti-adhesion barriers. The objective of our study was to investigate the impact of post-operative peri-hepatic adhesions on liver regeneration in patients who underwent TSH for unresectable CLM.

Anti-adhesive effect and safety of a thermosensitive adhesion barrier (Mediclore) for thyroid surgery: a double-blinded randomized controlled trial.

PurposePostoperative adhesions after thyroidectomy adversely affect patients’ quality of life. This study assessed the anti-adhesive effect and safety of thermosensitive sol-gel agents for patients undergoing thyroidectomy.MethodsA double-blind parallel-group randomized clinical trial involving patients aged 20–70 years undergoing thyroidectomy for thyroid nodules was conducted. From August 2017 to April 2020, 90 patients were randomly assigned to the experimental (n = 45, thermosensitive sol-gel agent applied to the surgical site) and control (n = 45, no treatment) groups in a 1:1 ratio. All patients were assessed using a questionnaire for swallowing difficulty, wrinkle problems, and inflammation at 2 weeks, 3 months, and 6 months after thyroid surgery. For reoperated patients, the degree of adhesion was evaluated according to the adhesion-evaluation score system (range, 0–4).ResultsDuring the follow-up period of 6.50 ± 1.38 months, the swallowing difficulty, wrinkle problem, and inflammation were improved in both groups. However, there was no statistically significant difference between the control and experimental groups related to swallowing difficulty, wrinkle problems, and inflammation. Two patients in the control group and 1 in the experimental group who underwent reoperation had an adhesion-evaluation score of 3 points. There were no adverse effects or allergic reactions.ConclusionA thermosensitive sol-gel agent can be safely used as an anti-adhesive barrier. However, this study did not reveal its efficacy for postoperative adhesions. A more objective and systematic study is required in the future.

Ingenuity of an intraperitoneal carry-in method (Hakama method) for an absorbable anti-adhesion barrier (regenerated cellulose oxide)

Ingenuity of an intraperitoneal carry-in method (Hakama method) for an absorbable anti-adhesion barrier (regenerated cellulose oxide)

Прогнозування ризику розвитку післяопераційної злукової кишкової непрохідності в дітей

Прогнозування ризику розвитку післяопераційної злукової кишкової непрохідності в дітей

Self-Healing Hydrogel Embodied with Macrophage-Regulation and Responsive-Gene-Silencing Properties for Synergistic Prevention of Peritendinous Adhesion.

Antiadhesion barriers such as films and hydrogels used to wrap repaired tendons are important for preventing the formation of adhesion tissue after tendon surgery. However, sliding of the tendon can compress the adjacent hydrogel barrier and cause it to rupture, which may then lead to unexpected inflammation. Here, a self-healing and deformable hyaluronic acid (HA) hydrogel is constructed as a peritendinous antiadhesion barrier. Matrix metalloproteinase-2 (MMP-2)-degradable gelatin-methacryloyl (GelMA) microspheres (MSs) encapsulated with Smad3-siRNA nanoparticles are entrapped within the HA hydrogel to inhibit fibroblast proliferation and prevent peritendinous adhesion. GelMA MSs are responsively degraded by upregulation of MMP-2, achieving on-demand release of siRNA nanoparticles. Silencing effect of Smad3-siRNA nanoparticles is around 75% toward targeted gene. Furthermore, the self-healing hydrogel shows relatively attenuated inflammation compared to non-healing hydrogel. The mean adhesion scores of composite barrier group are 1.67 ± 0.51 and 2.17 ± 0.75 by macroscopic and histological evaluation, respectively. The proposed self-healing hydrogel antiadhesion barrier with MMP-2-responsive drug release behavior is highly effective for decreasing inflammation and inhibiting tendon adhesion. Therefore, this research provides a new strategy for the development of safe and effective antiadhesion barriers.

Anti-adhesive barriers in clinical practice: personalized patient management

The adhesive process is an urgent problem of operative gynecology. The number of women suffering from complications of the adhesive process is growing every year, not to mention the deaths associated with this problem. Polygenic etiology, low efficiency of treatment of the adhesion process determined the priority of searching for methods to prevent the process of adhesion formation or, at least, to reduce the severity of postoperative adhesion, at least a decrease in the severity of postoperative adhesion. The review presents the current paradigm of the pathogenesis of the formation of postoperative adhesions and the possibility of preventing adhesive disorders in gynecological patients.

P-BN11 Patient Reported Outcomes of Phasix™ ST Mesh for Laparoscopic Hiatal Hernia Repair

Abstract Background Laparoscopic hiatal hernia repair continues to suffer from high recurrence rates, which has prompted the use of mesh reinforcement by some surgeons. Use of mesh however remains controversial due to its association with complications such as erosion, fibrosis and oesophageal stenosis. Biosynthetic Poly-4-Hydroxybutyrate Phasix™ ST mesh is an emerging technology which combines the durability of synthetic mesh with the remodelling characteristics of biologic mesh and includes an anti-adhesion hydrogel barrier. There is a paucity of patient reported outcome data for Phasix™ ST mesh. This study evaluates early patient reported outcomes following laparoscopic hiatal hernia repair with Phasix™ ST mesh. Methods Adult patients undergoing laparoscopic hiatal hernia repair with Phasix™ ST mesh between July 2020 to June 2021 at our institution were identified. Prospective data, including demographic data and complication rates, was collected from electronic and paper medical records. The 12-Item Short Form Survey (SF-12) was administered to assess quality of life pre-operatively and post-operatively with a minimum 30-day follow-up. Results Fourteen patients (12 female, one male) were included with a median age of 66 years (range 52-79). There were no intraoperative complications, mesh-related complications, re-operation, re-admission, or recurrence at a median follow-up of 4 months (IQR 4.0). Median physical health component (PHC) score was 32.7 (IQR 6.2) at baseline and increased to 41.6 (IQR 13.7) post-operatively. Median difference in PHC score was +11.4 (IQR 10.7). Median mental health component (MHC) score was 39.8 (IQR 12.5) at baseline and increased to 57.4 (IQR 8.2) post-operatively. Mean difference in MHC score was +17.7 (IQR 15.9). Conclusions To our knowledge, this is the first report of outcomes on the use of Phasix™ ST mesh for laparoscopic hiatal hernia repair in the United Kingdom. Our study found that it is associated with improvements in both physical and mental quality of life in the short-term post-operative follow-up, although there is some variation in the degree of improvement reported.

Evaluation of In Vivo Adhesion Properties of New Generation Polyglactin, Oxidized Regenerated Cellulose and Chitosan-Based Meshes for Hernia Surgery.

IntroductionComposite meshes coated with anti-adhesive barriers have been developed by taking advantage of the robustness of polypropylene meshes for use in hernia repair. We aimed to evaluate the effects of composite meshes containing polyglactin, polycaprolactone, oxidized regenerated cellulose and chitosan on the adhesion formation.MethodsForty-two Sprague Dawley male rats were divided into six groups of seven rats according to the content of the meshes used. A defect was created on the right abdominal wall of the rats and an oval composite mesh of 2 cm in diameter was placed over the defect and fixed. The rats were sacrificed under anesthesia on the 7th postoperative day. Macroscopic and histopathological examination was performed and the incorporation of the mesh with the abdominal wall and the presence of intraabdominal adhesions were evaluated.ResultsWhen the macroscopic findings of the rats were evaluated, there was a statistically significant difference between the rat groups in terms of the distribution of peritoneal adhesion scores (p<0.05). There was no statistically significant difference between the rat groups in terms of the distribution of inflammation, fibrosis and macrophage levels (p>0.05).ConclusionIt was evaluated that the development of intraabdominal adhesion and the strength of adhesion decreased when biocompatible adhesion barriers with anti-adhesive properties such as oxidized regenerated cellulose and chitosan were used in the structure of composite meshes used in hernia repair. Hemostatic and antibacterial properties of these substances are promising to create the ideal mesh.

Effect of glutaraldehyde-crosslinked cartilage acellular matrix film on anti-adhesion and nerve regeneration in a rat sciatic nerve injury model.

Decellularized extra-cellular matrix (ECM) has been studied as an alternative to anti-adhesive biomaterials and cartilage acellular matrix (CAM) has been shown to inhibit postoperative adhesion in several organs. This study aimed to evaluate the suitability of glutaraldehyde (GA) crosslinked CAM-films as anti-adhesion barriers for peripheral nerve injury. The films were successfully fabricated and showed improved physical properties such as mechanical strength, swelling ratio, and lengthened degradation period while maintaining the microstructure and chemical composition after GA crosslinking. In the in vitro study of CAM-film, the dsDNA content met the recommended limit of decellularization and more than 70% of the major ECM components were preserved after decellularization. The adhesion and proliferation of seeded human umbilical vein endothelial cells and fibroblasts were significantly lower in CAM-film than in control, but similar with Seprafilm. However, the CAM-film extract did not show cytotoxicity. In the in vivo study, the peri-neural fibrosis was thicker, adhesion score higher, and peri-neural collagen fibers more abundant in the control group than in the CAM-film group. The total number of myelinated axons was significantly higher in the CAM-film group than in the control group. The inflammatory marker decreased with time in the CAM-film group compared to that in the control group, whereas the nerve regenerative marker expression was maintained. Moreover, the ankle angles at contracture and toe-off were higher in the CAM film-treated rats than in the control rats. GA-crosslinked CAM films may be used during peripheral nerve surgery to prevent peri-neural adhesion and enhance nerve functional recovery.

Application of Bioactive Hydrogels for Functional Treatment of Intrauterine Adhesion.

Intrauterine adhesion (IUA) is a common endometrial disease and one of the main causes of infertility in women of childbearing age. Current treatment strategies, such as hysteroscopic adhesion resection, hysteroscopic transcervical resection of adhesion (TCRA), the use of local hormone drugs, and anti-adhesion scaffold implantation, do not provide a satisfactory pregnancy outcome for moderate-severe IUA, which presents a great challenge in reproductive medicine. With the development of material engineering, various bioactive and functional hydrogels have been developed using natural and synthetic biomaterials. These hydrogels are not only used as barely physical barriers but are also designed as vectors of hormone drugs, growth factors, and stem cells. These characteristics give bioactive hydrogels potentially important roles in the prevention and treatment of IUA. However, there is still no systematic review or consensus on the current advances and future research direction in this field. Herein, we review recent advances in bioactive hydrogels as physical anti-adhesion barriers, in situ drug delivery systems, and 3D cell delivery and culture systems for seeded cells in IUA treatment. In addition, current limitations and future perspectives are presented for further research guidance, which may provide a comprehensive understanding of the application of bioactive hydrogels in intrauterine adhesion treatment.

Physically Cross-Linked Hyaluronan-Based Ultrasoft Cryogel Prepared by Freeze-Thaw Technique as a Barrier for Prevention of Postoperative Adhesions.

Postsurgical peritoneal adhesions are a common and serious postoperative complication after various peritoneal surgeries, such as pelvic and abdominal surgery. Various studies have shown that peritoneal adhesions can be minimized or prevented by physical anti-adhesion barriers, including membranes, knits, and hydrogels. Hydrogels have attracted great attention in preventing peritoneal adhesions because the dimensional architecture of hydrogels is similar to that of the native extracellular matrix. However, chemical cross-linkers had to be used in the preparation of chemical hydrogels, which may have problems in cytotoxicity or unwanted side effects. This fact prompts us to create alternative cross-linking methods for the development of biocompatible hydrogels as physical barriers. Herein, we report a physically cross-linked flexible hyaluronan (HA) cryogel prepared via a freeze-thaw technique as a novel anti-adhesion biomaterial for completely preventing postsurgical peritoneal adhesions. In vitro studies demonstrated that this physically cross-linked HA cryogel exhibited excellent biocompatibility, the inherently desirable biocompatibility and functionality of HA being integrally retained as much as possible. Intriguingly, the rheological properties and appropriate biodegradability of the cryogels were readily tailored and tunable by way of the gelation process. In vivo assessments suggested that the cryogel, as a physical barrier, satisfactorily prevented fibroblast penetration and attachment between the injured tissues and nearby normal organs. Furthermore, the molecular mechanism studies revealed that the HA cryogel could prevent peritoneal adhesion by inhibiting inflammatory response and modulation of the fibrinolytic system. Our results show that HA ultrasoft cryogel is a promising clinical candidate for prolonged adhesion prevention.