PP mesh is a widely used prosthetic material in hernia repair. However, visceral adhesion is one of the worst complications of this operation. Hence, an anti-adhesive PP mesh is developed by coating porous polyvinyl alcohol (PVA) hydrogel on PP surface via freezing-thawing process method. The compressive modulus of porous PVA hydrogel coating is first regulated by the addition of porogen sodium bicarbonate (NaHCO3) at various quality ratios with PVA. As expected, the porous hydrogel coating displayed modulus more closely resembling that of native abdominal wall tissue. In vitro tests demonstrate the modified PP mesh show superior coating stability, excellent hemocompatibility, and good cytocompatibility. In vivo experiments illustrate that PP mesh coated by the PVA4 hydrogel that mimicked the modulus of native abdominal wall could prevent adhesion effectively. Based on this, the rapamycin (RPM) is loaded into the porous PVA4 hydrogel coating to further improve anti-adhesive property of PP mesh. The Hematoxylin and eosin (H&E) and Masson trichrome (MT) staining results verified that the resulting mesh could alleviate the inflammation response and reduce the deposition of collagen around the implantation zone. The biomimetic mechanical property and anti-adhesive property of modified PP mesh make it a valuable candidate for application in hernioplasty.

The development of anti-adhesion hydrogels for preventing postoperative adhesions is an ongoing challenge, particularly in achieving a balance between exceptional antifouling properties and effective in situ tissue retention. In this study, we propose a unique approach with the design of a single-component Janus zwitterionic hydrogel patch featuring a bionic microstructure. The Janus patches were prepared through free radical polymerization of sulfobetaine methacrylate with N, N\'-methylenebis(2-propenamide) as the cross-linker. The incorporation of hexagonal facets separated by interconnecting grooves on one side imparts durable and reliable in situ retention capabilities to the Janus hydrogel patch when it is applied to traumatized tissues. The opposing flat surface exhibits outstanding resistance to bacteria, proteins, and cell adhesion, due to the superhydrophilicity and excellent antifouling characteristics of zwitterionic polymers. This dual functionality empowers the Janus hydrogel patch to mitigate adhesions between traumatized and surrounding tissues. The hexagonal and groove bionic microstructures facilitate rapid drainage, promoting swift contact with the tissue for increased adhesion strength, while independent hexagonal microfacets enhance the peeling energy. In an in vivo setting, Janus zwitterionic hydrogel patches with surface microstructures form mutually embedded structures with the cecum surface, minimizing the likelihood of slippage and detachment. Remarkably, in vivo experiments involving abdominal wall cecum injuries illustrate the Janus zwitterionic hydrogel patch\'s superior anti-adhesion effectiveness compared to commercial controls. Thus, the Janus hydrogel patch, distinguished by its bionic microstructure surface, presents substantial potential in the biomedical field for averting postoperative adhesions.

Postoperative adhesion is a noteworthy clinical complication in abdominal surgery due to the existing physical barriers are unsatisfactory and inefficient in preventing its occurrence. In this work, an elaborate nanoparticle-in-microgel system (nMGel) is presented for postoperative adhesion prevention. nMGel is facilely formed by crosslinking manganese dioxide (MnO2) nanoparticles-loaded gelatin microspheres with polydopamine using a modified emulsification-chemical crosslinking method, generating a nano-micron spherical hydrogel. After drying, powdery nMGel with sprayability can perfectly cover irregular wounds and maintains robust tissue adhesiveness even in a wet environment. Additionally, nMGel possesses prominent antioxidant and free radical scavenging activity, which protects cell viability and preserves cell biological functions in an oxidative microenvironment. Furthermore, nMGel displays superior hemostatic property as demonstrated in mouse tail amputation models and liver trauma models. Importantly, nMGel can be conveniently administrated in a mouse cecal defect model to prevent adhesion between the injured cecum and the peritoneum by reducing inflammation, oxidative stress, collagen synthesis, and angiogenesis. Thus, the bioactive nMGel offers a practical and efficient approach for ameliorating postsurgical adhesion.

Postsurgical adhesions are a common complication of surgical procedures that can lead to postoperative pain, bowel obstruction, infertility, as well as complications with future procedures. Several agents have been developed to prevent adhesion formation, such as barriers, anti-inflammatory and fibrinolytic agents. The Food and Drug Administration (FDA) has approved the use of physical barrier agents, but they have been associated with conflicting clinical studies and controversy in the clinical utilization of anti-adhesion barriers. In this review, we summarize the human anatomy of the peritoneum, the pathophysiology of adhesion formation, the current prevention agents, as well as the current research progress on adhesion prevention. The early cellular events starting with injured mesothelial cells and incorporating macrophage response have recently been found to be associated with adhesion formation. This may provide the key component for developing future adhesion prevention methods. The current use of physical barriers to separate tissues, such as Seprafilm®, composed of hyaluronic acid and carboxymethylcellulose, can only reduce the risk of adhesion formation at the end stage. Other anti-inflammatory or fibrinolytic agents for preventing adhesions have only been studied within the context of current research models, which is limited by the lack of in-vitro model systems as well as in-depth study of in-vivo models to evaluate the efficiency of anti-adhesion agents. In addition, we explore emerging therapies, such as gene therapy and stem cell-based approaches, that may offer new strategies for preventing adhesion formation. In conclusion, anti-adhesion agents represent a promising approach for reducing the burden of adhesion-related complications in surgical patients. Further research is needed to optimize their use and develop new therapies for this challenging clinical problem.

Postoperative peritoneal adhesion is a common complication after surgery with high morbidity. In addition to improving surgical operations, medical therapy and physical barriers are the two main ways to prevent postoperative peritoneal adhesion. Satisfactory efficacy is not often obtained by the single antiadhesion method, and the combination of barrier therapy and antiadhesion drugs has attracted more attention. In this study, we first demonstrated that aberrant complement activation was associated with peritoneal injury and inflammatory responses. Correspondingly, blocking the C5a-C5aR axis reaction effectively reduced inflammatory reactions. Therefore, we creatively developed an integrated treatment of xyloglucan derivative (mXG) hydrogel and intravenous anti-C5a receptor antibody (anti-C5aRab) aimed at peritoneal adhesion, and then systematically evaluated the therapeutic efficacy using a sidewall defect-cecum abrasion model in mice. In vitro and in vivo experiments showed that the mXG hydrogel had good biocompatibility and degradability and could serve as a safe anti-adhesion barrier. The results showed that anti-C5aRab treatment could significantly inhibit peritoneal adhesions by reducing neutrophil infiltration and the expression of phosphorylated Smad2. Taken together, the mXG hydrogel integrated with anti-C5aRab showed superior antiadhesion performance and holds promising clinical applications in preventing peritoneal adhesion. STATEMENT OF SIGNIFICANCE: Postoperative peritoneal adhesion is an urgent problem to be solved after surgery. Previously, a biodegradable and thermoreversible xyloglucan derivative (mXG) hydrogel was developed that effectively prevented postoperative peritoneal adhesions, but obvious inflammatory responses and proliferation could still be observed. In addition, aberrant complement activation is associated with a variety of inflammatory diseases. We demonstrated that aberrant complement activation is involved in peritoneal adhesion. In this work, mXG hydrogel and intravenous anti-C5a receptor antibody (anti-C5aRab) were integrated to address peritoneal adhesions. The anti-C5aRab reduced the inflammatory responses. In addition, the mXG hydrogel was easy to use and effectively isolated the wound surface at the local injury site. Overall, this integrated treatment significantly improved the antiadhesion effect.

Anastomosis surgery at the intestinal site is performed on millions of individuals every year. However, several persistent complications, such as anastomotic leakage, abnormal adhesion, and anastomotic stenosis, have been observed after the surgery. For promoting anastomotic healing and to overcome the challenges mentioned above, re-epithelialization at anastomotic sites is crucial. In this study, an epithelialization-promoting macromolecular prodrug Ala-Gln-PPDO was prepared and processed into fibrous membranes by electrospinning. Ala-Gln and gentamicin were sustainably released from the electrospun membranes with degradation of these membranes to promote the proliferation of rat intestinal epithelial cells and suppress the proliferation of Staphylococcus aureus and Escherichia coli. The comprehensive repair effects of Ala-Gln-PPDO membranes have been evaluated in rat models of intestinal anastomosis in this study. Application of Ala-Gln-PPDO membranes, especially the gentamicin-incorporated Ala-Gln-PPDO ones, could prevent adhesion between the injured intestine and surrounding intestinal tissues. In addition, they did not affect the healing strength of anastomotic stoma negatively and could promote re-epithelialization at the anastomotic sites. Furthermore, the gentamicin-incorporated Ala-Gln-PPDO membranes could relieve stenosis at anastomotic sites. The gentamicin-incorporated Ala-Gln-PPDO electrospun membrane is a promising, comprehensive implantable material for promoting healing after gastrointestinal anastomosis owing to its effects involving the promotion of re-epithelialization, prevention of adhesion, and relieving of anastomotic stenosis.

Partial liver resection is an established treatment for hepatic disorders. However, surgical bleeding, intra-abdominal adhesion and rapid liver regeneration are still major challenges after partial liver resection, associated with morbidity and mortality. Herein, a biomimetic hybrid hydrogel, composed of oxidized hyaluronic acid, glycol chitosan and MenSCs-derived conditioned medium (CM), is presented to address these issues. The hybrid hydrogel is formed through reversible Schiff base, and possesses injectability and self-healing capability. Moreover, hybrid hydrogel exhibits the capabilities of hemostasis, anti-infection, tissue adhesion and controllable release of cargoes. Based on in vivo studies of the multifunctional hybrid hydrogel, it is demonstrated that acute bleeding in partial liver resection can be ceased immediately by virtue of the hemostasis features of hybrid hydrogel. Also, a significant reduction of intra-abdominal adhesion is confirmed in hybrid hydrogel-treated resection surface. Furthermore, upon the treatment of hybrid hydrogel, hepatic cell proliferation and tissue regeneration can be significantly improved due to the controllably released cytokines from MenSCs-derived CM, exerting the effects of mitogenesis and anti-inflammation in vivo. Thus, the biomimetic hybrid hydrogel can be a promising candidate with great potential for application in partial liver resection.

Dura mater defect and subsequent cerebrospinal fluid (CSF) leakage usually appear in trauma or neurosurgical procedures and are followed by a series of serious complications and even death. The use of a qualified dura mater substitute with multifunction of leakage blockade, adhesion prevention, and dura reconstruction is one of the promising treatment methods. However, even though some products have been used in the clinic, none of the substitutes achieved the required multifunction. In this study, we aimed to design and fabricate a dura repair composite with the ideal multifunction. By biomimicking the structure and component of natural dura, we applied poly(L-lactic acid) (PLLA), chitosan (CS), gelatin, and acellular small intestinal submucosa (SIS) powders to successfully prepare a triple-layered composite. Then, a series of specific devices and techniques were developed to investigate the performance. The results revealed that satisfactory structural stability could be realized under good synergistic interactions among the components. In addition, all the findings suggested that the bionic triple-layered composite showed satisfactory multifunction of leakage blockade, adhesion prevention, antibacterial property, and dura reconstruction potential, and thus, it might be a promising candidate for dura repair. STATEMENT OF SIGNIFICANCE: Developing qualified dura mater substitutes with multifunction of leakage blockade, adhesion prevention, and dura reconstruction is crucial for treating dura mater defect and subsequent cerebrospinal fluid (CSF) leakage that appear in trauma or neurosurgical procedures. In this study, we designed and fabricated a triple-layered dura repair biocomposite with satisfactory structural stability and desired multifunction based on biomimicking of the structure and component of natural dura. Moreover, a series of specific devices and techniques were developed to investigate the relevant performance. Overall, the developed hydrogel electrospinning system exhibited excellent advantages in achieving multifunction and could be applied widely in the future to achieve multifunctional tissue repair materials.

Tissue adhesion is a severe postoperative complication. Various strategies have been developed to minimize postoperative adhesion, but the clinical efficacy is still far from satisfactory. Herein, we present a dual dynamically crosslinked hydrogel to serve as a physical postoperative anti-adhesion barrier. The hydrogel was generated by dynamic chemical oxime bonding from alkoxyamine-terminated Pluronic F127 (AOP127) and oxidized hyaluronic acid (OHA), as well as hydrophobic association of AOP127. Rheological analysis demonstrated that the hydrogel exhibits temperature sensitivity. At 37 °C, it shows much higher modulus and higher stability than the Pluronic F127 hydrogel. Hemolytic assays suggested that the hydrogel undergoes low hemolysis. In addition, it exhibited anti-adhesion to blood cells in blood cell adhesion tests. It also showed an anti-attachment effect to fibroblasts and biocompatibility in vitro cell studies. Macroscopic evaluation and lap-shear tests revealed that the hydrogel has a moderate adhesive capacity to tissue, which is important for self-fixation. A rat model of sidewall defect-bowel abrasion was established to evaluate the anti-adhesion effect in vivo. The gross observation and pathological analysis revealed a significant reduction in postoperative peritoneal adhesion in the AOP127/OHA hydrogel-treated group than those treated with normal saline or Pluronic F127 hydrogel. Hence, the dual dynamically crosslinked hydrogel with self-fixable capacity may be suitable as a physical barrier for postoperative adhesion prevention. STATEMENT OF SIGNIFICANCE: Despite the development of numerous postoperative anti-adhesion barriers, their anti-adhesion efficacy is still limited in clinical trials due to poor tissue adhesion and rapid clearance from injured areas. Herein, we have developed a dual dynamic crosslinked hydrogel, generated by dynamic oxime bonds and hydrophobic interactions. The hydrogel is temperature-sensitive and demonstrates moderate tissue adhesion capacity, which allows for self-fixation when applied to defects. The introduction of dynamic covalent bonds improves the stability of the hydrogel. Moreover, the hydrogel not only displays appropriate hemocompatibility, cytocompatibility and anti-adhesion of blood cells and fibroblasts, but it also effectively contributes to preventing postoperative peritoneal adhesions in vivo. Hence, this dual dynamic crosslinked hydrogel may have potential applications as a physical barrier in clinical practice.

Sustained delivery of small interfering RNA (siRNA) is a challenge in gene silencing for managing gene-related disorders. Although nanoparticle-mediated electrospun fibers enable sustainable gene silencing, low efficiency, loss of biological activity, toxicity issues, and complex electrospinning techniques are all bottlenecks of these systems. Preventing peritendinous adhesion is crucial for their successful use, which involves blocking cellular signaling via physical barriers. Here, a multifunctional, yet structurally simple, cationic 2,6-pyridinedicarboxaldehyde-polyethylenimine (PDA)-mediated extracellular signal-regulated kinase (ERK)2-siRNA polymeric delivery system is reported, in the form of peritendinous antiadhesion electrospun poly-l-lactic acid/hyaluronan membranes (P/H), with the ability to perform sustained release of bioactive siRNA for long-term prevention of adhesions and ERK2 silencing. After 4 days of culture, the cell area and proliferation rate of chicken embryonic fibroblasts on siRNA+PDA+P/H membrane are significantly less than those on P/H and siRNA+P/H membranes. The in vivo results of average optical density of collagen type III (Col III) and gene expression of ERK2 and its downstream SMAD3 in the siRNA+PDA+P/H group are less than those of P/H and siRNA+P/H groups. Consequently, siRNA+PDA+P/H electrospun membrane can protect the bioactivity of ERK2-siRNA and release it in a sustained manner. Moreover, adhesion formation is inhibited by reducing fibroblast proliferation and Col III deposition, and downregulating ERK2 and its downstream SMAD3.