Postoperative Tissue Adhesion Research Articles

A tough Janus poly(vinyl alcohol)-based hydrogel for wound closure and anti postoperative adhesion

Traditional adhesive hydrogels perform well in tissue adhesion but they fail to prevent postoperative tissue adhesion. To address this challenge, a biodegradable Janus adhesive hydrogel (J-AH) was designed and fabricated by the assembly of three different functional layers including anti-adhesive layer, reinforceable layer, and wet tissue adhesive layer. Each layer of J-AH serves a specific function: the top zwitterionic polymeric anti-adhesive layer shows superior resistance to cell/protein and tissue adhesion; the middle poly(vinyl alcohol)/tannic acid reinforceable matrix layer endows the hydrogel with good mechanical toughness of ∼2.700 MJ/m3; the bottom poly(acrylic acid)/polyethyleneimine adhesive layer imparts tough adhesion (∼382.93 J/m2 of interfacial toughness) to wet tissues. In the rat liver and femoral injury models, J-AH could firmly adhere to the bleeding tissues to seal the wounds and exhibit impressive hemostatic efficiency. Moreover, in the in vivo adhesion/anti-adhesion assay of J-AH between the defected cecum and peritoneal walls, the top anti-adhesive layer can effectively inhibit undesired postoperative abdominal adhesion and inflammatory reaction. Therefore, this research may present a new strategy for the design of advanced bio-absorbable Janus adhesive hydrogels with multi-functions including tissue adhesion, anti-postoperative adhesion and biodegradation. Statement of significanceDespite many adhesive hydrogels with tough tissue adhesion capability have been reported, their proclivity for undesired postoperative adhesion remains a serious problem. The postoperative adhesion may lead to major complications and even endanger the lives of patients. The injectable hydrogels can cover the irregular wound and suppress the formation of postoperative adhesion. However, due to the lack of adhesive properties with tissue, it is difficult for the hydrogels to maintain on the wound surface, resulting in poor anti-postoperative adhesion effect. Herein, we design a Janus adhesive hydrogel (J-AH). J-AH integrates together robust wet tissue adhesion and anti-postoperative adhesion. Therefore, this research may present a new strategy for the design of advanced bio-absorbable Janus adhesive hydrogels.

Bletilla striata Polysaccharide-Containing Carboxymethyl Cellulose Bilayer Structure Membrane for Prevention of Postoperative Adhesion and Achilles Tendon Repair.

Postoperative tissue adhesion and poor tendon healing are major clinical problems associated with tendon surgery. To avoid postoperative adhesion and promote tendon healing, we developed and synthesized a membrane to wrap the surgical site after tendon suturing. The bilayer-structured porous membrane comprised an outer layer [1,4-butanediol diglycidyl ether cross-linked with carboxymethyl cellulose (CX)] and an inner layer [1,4-butanediol diglycidyl ether cross-linked with Bletilla striata polysaccharides and carboxymethyl cellulose (CXB)]. The morphology, chemical functional groups, and membrane structure were determined. In vitro experiments revealed that the CX/CXB membrane demonstrated good biosafety and biodegradability, promoted tenocyte proliferation and migration, and exhibited low cell attachment and anti-inflammatory effects. Furthermore, in in vivo animal study, the CX/CXB membrane effectively reduced postoperative tendon-peripheral tissue adhesion and improved tendon repair, downregulating inflammatory cytokines in the tendon tissue at the surgical site, which ultimately increased tendon strength by 54% after 4 weeks.

Polysaccharide-based emulsion gels for the prevention of postoperative adhesions and as a drug delivery system using 5-fluorouracil

Postoperative tissue adhesion is a well-recognized and common complication. Despite ongoing developments in anti-adhesion agents, complete prevention remains a challenge in clinical practice. Colorectal cancer necessitates both adhesion prevention and postoperative chemotherapy. Accordingly, drug-loading into an anti-adhesion agent could be employed as a treatment strategy to maximize the drug effects through local application and minimize side effects. Herein, we introduce an anti-adhesion agent that functions as a drug delivery system by loading drugs within an emulsion that forms a gel matrix in the presence of polysaccharides, xanthan gum, and pectin. Based on the rheological analysis, the xanthan gum-containing emulsion gel formed a gel matrix with suitable strength and mucosal adhesiveness. In vitro dissolution tests demonstrated sustained drug release over 12 h, while in vivo pharmacokinetic studies revealed a significant increase in the Tmax (up to 4.03 times) and area under the curve (up to 2.62 times). However, most of the drug was released within one day, distributing systemically and raising toxicity concerns, thus limiting its efficacy as a controlled drug delivery system. According to in vivo anti-adhesion efficacy evaluations, the xanthan gum/pectin emulsion gels, particularly F2 and F3, exhibited remarkable anti-adhesion capacity (P < 0.01). The emulsion gel formulation exhibited no cytotoxicity against fibroblasts or epithelial cell lines. Thus, the xanthan gum/pectin emulsion gel exhibits excellent anti-adhesion properties and could be developed as a drug delivery system.

Harnessing bi-layered supramolecular Janus tissue-adhesive/anti-adhesive fibrous hydrogel for efficient hemostasis, wound healing, and suppressing postoperative tissue adhesion

Inadequate progression of primary (bleeding/infection) and secondary (rebleeding/postoperative tissue adhesion) complications at the wound site pose a substantial burden of morbidity and mortality worldwide. Therefore, developing a multifunctional biomaterial dressing for abrupt tissue adhesion and suppressed postoperative adhesion simultaneously is deemed essential. Herein, we designed a bi-layered Janus fibrous hydrogel (J-FH). The bottom layer comprises zinc-incorporated mesoporous silica nanogranules (ZnMSG) reinforced catechol-modified gelatin methacrylate (GC) hydrogel. GC@ZnMSG supramolecular hydrogel easily adheres to wet wounded tissue and possesses hemostatic, mechanical, and antibacterial properties. On the other hand, the top layer comprises dopamine-modified cellulose acetate nanofibrous membrane (DC) sequentially deposited with polydopamine-conjugated zwitterionic sulfobetaine methacrylate (PDA-SBMA). DC@PDA-SBMA fibrous membrane performs the anti-adhesive function by suppressing fouling and preventing tissue adhesion. The findings of animal experiments show that the bottom layer of the J-FH adheres firmly to the tissue surface, preventing bleeding and supporting tissue closure/regeneration. In contrast, the top layer provides mechanical stability, preventing secondary bleeding and suppressing postoperative tissue adhesion. Overall, J-FH demonstrated excellent biocompatibility, antibacterial properties, superior mechanical strength, asymmetric adhesion, robust hemostasis, and accelerated wound healing. It can replace traditional sutures, non-degradable dressings, and double-sided adhesive scaffolds for hemostasis, external, and internal postoperative wound healing.

Injectable polyamide-amine dendrimer-crosslinked meloxicam-containing poly-γ-glutamic acid hydrogel for prevention of postoperative tissue adhesion through inhibiting inflammatory responses and balancing the fibrinolytic system

Establishing a physical barrier between the peritoneum and the cecum is an effective method to reduce the risk of postoperative abdominal adhesions. Meloxicam (MX), a nonsteroidal anti-inflammatory drug has also been applied to prevent postoperative adhesions. However, its poor water solubility has led to low bioavailability. Herein, we developed an injectable hydrogel as a barrier and drug carrier for simultaneous postoperative adhesion prevention and treatment. A third-generation polyamide-amine dendrimer (G3) was exploited to dynamically combine with MX to increase the solubility and the bioavailability. The formed G3@MX was further used to crosslink with poly-γ-glutamic acid (γ-PGA) to prepare a hydrogel (GP@MX hydrogel) through the amide bonding. In vitro and in vivo experiments evidenced that the hydrogel had good biosafety and biodegradability. More importantly, the prepared hydrogel could control the release of MX, and the released MX is able to inhibit inflammatory responses and balance the fibrinolytic system in the injury tissues in vivo. The tunable rheological and mechanical properties (compressive moduli: from ∼ 57.31 kPa to ∼ 98.68 kPa;) and high anti-oxidant capacity (total free radical scavenging rate of ∼ 94.56 %), in conjunction with their syringeability and biocompatibility, indicate possible opportunities for the development of advanced hydrogels for postoperative tissue adhesions management.

Lecithin-complexed oregano essential oil-encapsulated fibrous barriers prevent postoperative adhesions by regulating Nrf2/NF-κB signaling pathways

Postoperative adhesions are prone to a variety of complications, which can adversely affect the quality of life (QOL) of patients. While anti-adhesion scaffolds rapidly degrade, foreign body reactions (FBR), exaggerated inflammatory reactions, and oxidative stress may increase tissue adhesions. This necessitates the development of anti-adhesion scaffolds with multifunctional anti-inflammatory, anti-bacterial, and anti-oxidative characteristics. The objective of this study was to simultaneously leverage natural antimicrobial and anti-oxidative bioactive molecules, such as lecithin (L) and Oregano essential oil (O) to afford poly(lactic-co-glycolic acid) (PLGA)-based electrospun membranes for postoperative anti-adhesion management. A series of assays revealed a beneficial effect of L and O co-loaded membranes (P@LO) to suppress bacterial growth, reduce the proliferation of fibroblasts, and confer anti-oxidative and anti-inflammatory functionalities to membranes than that of the control (P) or only a single cue-loaded groups (P@L and P@O). The underlying molecular mechanism of the anti-inflammatory effect may be an upregulation of the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation. An assessment of membranes in an abdominal and a tendon adhesion model showed a significant effect of P@LO membranes to prevent post-operative tissue adhesion. The P@LO membranes were found to up-regulate the phosphorylation of Nrf2 while down-regulate the phosphorylation of nuclear factor kappa-B (NF-κB) P65. This resulted in lower expression of collagen Ⅰ (Col-Ⅰ), collagen Ⅲ (Col-Ⅲ), and alpha-smooth muscle actin (α-SMA) alongside inflammation resolution and less transition of fibroblasts to myofibroblasts. Taken together, these multifunctional scaffolds may have broad implications for postoperative adhesion management.

Multi-functional dual-layer nanofibrous membrane for prevention of postoperative pancreatic leakage

Postoperative pancreatic leakage due to pancreatitis in patients is a life-threatening surgical complication. The majority of commercial barriers are unable to meet the demands for pancreatic leakage due to poor adhesiveness, toxicity, and inability to degrade. In this study, we fabricated mitomycin-c and thrombin-loaded multifunctional dual-layer nanofibrous membrane with a combination of alginate, PCL, and gelatin to resolve the leakage due to suture line disruption, promote hemostasis, wound healing, and prevent postoperative tissue adhesion. Electrospinning was used to fabricate the dual-layer system. The study results demonstrated that high gelatin and alginate content in the inner layer decreased the fiber diameter and water contact angle, and crosslinking allowed the membrane to be more hydrophilic, making it highly biodegradable, and adhering firmly to the tissue surfaces. The results of in vitro biocompatibility and hemostatic assay revealed that the dual-layer had a higher cell proliferation and showed effective hemostatic properties. Moreover, the in vivo studies and in silico molecular simulation indicated that the dual layer was covered at the wound site, prevented suture disruption and leakage, inhibited hemorrhage, and reduced postoperative tissue adhesion. Finally, the study results proved that dual-layer multifunctional nanofibrous membrane has a promising therapeutic potential in preventing postoperative pancreatic leakage.

A Janus adhesive hydrogel sheet for preventing postoperative tissue adhesion of intestinal injuries.

Although adhesive hydrogels represent an alternative to surgical sutures for non-invasive tissue wound sealing, those with indiscriminate adhesion fail to hold wounds while inhibiting postoperative tissue adhesion, thus limiting their application in intestinal repair. In this study, an asymmetric adhesive hydrogel sheet composed mainly of polyacrylic acid (PAA) and gelatin (GA) that can be wet-adhered to the surface of intestinal tissue was developed. One side of the GA-PAA hydrogel sheet was complexed with polyvinyl alcohol (PVA), which shielded the excess adhesion based on a physical barrier. Both sides of the PVA/GA-PAA hydrogel showed distinct adhesive and antiadhesive properties. Intriguingly, the anti-adhesive side showed significant anti-adhesion toward specific proteins. The results of animal experiments showed that the PVA/GA-PAA hydrogel could firmly adhere to the intestine to stop leakage and prevent post-operative tissue adhesion two weeks after surgery. The hematoxylin and eosin (H&E) staining results showed that the damaged intestinal serosa was repaired without tissue adhesion. It is believed that the controllable adhesion of the adhesive hydrogel offers better prospects for intestinal repair.

A Janus hydrogel sealant with instant wet adhesion and anti-swelling behavior for gastric perforation repair

Achieving instant adhesion on wet tissues and preventing the concurrently occurred postoperative tissue adhesion remain tough challenges but urgently demanded. And the deteriorated cohesion and adhesion caused by undesired swelling of hydrogel could not be ignored. Herein, we developed a Janus hydrogel with instant wet adhesion and anti-swelling behavior, based on poly (acrylic acid) (PAA), gelatin (GT) and hyperbranched polymers modified with catechol (HBPC). The asymmetric structure is achieved through complexed one-side of the hydrogel with cationic polymers. The strong physical interaction between PAA and GT formed during immersing in water enhanced the mechanical strength of the gels. And the hydrogel exhibits good anti-swelling behavior, which circumvents the limitations of conventional hydrogel caused by swelling. Water drainage induced by hydrophobic component and the following removal of water residuals achieved by hydrophilic PAA synergistically enhanced the instant wet adhesion of the hydrogel. Besides, pH-responsive protonation of carboxyl groups in PAA equipped the adhesive with extreme acid-tolerance. The in vivo evaluation results demonstrated that the asymmetric adhesive hydrogel could promote the repair of gastric perforation while reducing the risk of postoperative tissue adhesion. The hydrogel with asymmetric wet adhesion might provide valuable insights into the establishment of bioadhesives for gastric sealing and repair.

An Integrated Asymmetric Wet Adhesive Hydrogel with Gradient Charge Distribution Induced by Electrostatic Field

AbstractAdhesive hydrogels have been applied in biomedical field as an alternative to surgical sutures. However, there still exist rigorous challenges in rough underwater adhesion and asymmetric adhesion of hydrogels, especially applied in wound healing and organ repair in vivo. Herein, a strategy is proposed to prepare integrated hydrogels with asymmetric underwater adhesion capability by forming the asymmetric electrical interface under an electrostatic field. The synergistic effects between catechol and amine and complex coacervation are used to improve the underwater adhesion of hydrogel. Furthermore, by applying an electrostatic field, the cations and anions in solution of monomers are separated to form asymmetric adhesion interfaces. The hydrogel exhibits obvious asymmetric underwater adhesion ability on porcine skin with a strong adhesive strength of 97 kPa on cation side and 25 kPa on the anion side. Animal experiment outcomes reveal that only one side of the asymmetric hydrogel could adhere firmly to the rat liver and the rabbit stomach, while the other side could not effectively prevent postoperative tissue adhesion. The asymmetric distribution of adhesive molecules induced by electrostatic fields will provide a new alternative for designing and adjusting asymmetric adhesives after surgery.

A sandwiched patch toward leakage-free and anti-postoperative tissue adhesion sealing of intestinal injuries.

Ideal repair of intestinal injury requires a combination of leakage-free sealing and postoperative antiadhesion. However, neither conventional hand-sewn closures nor existing bioglues/patches can achieve such a combination. To this end, we develop a sandwiched patch composed of an inner adhesive and an outer antiadhesive layer that are topologically linked together through a reinforced interlayer. The inner adhesive layer tightly and instantly adheres to the wound sites via -NHS chemistry; the outer antiadhesive layer can inhibit cell and protein fouling based on the zwitterion structure; and the interlayer enhances the bulk resilience of the patch under excessive deformation. This complementary trilayer patch (TLP) possesses a unique combination of instant wet adhesion, high mechanical strength, and biological inertness. Both rat and pig models demonstrate that the sandwiched TLP can effectively seal intestinal injuries and inhibit undesired postoperative tissue adhesion. The study provides valuable insight into the design of multifunctional bioadhesives to enhance the treatment efficacy of intestinal injuries.

An Adhesive/Anti-Adhesive Janus Tissue Patch for Efficient Closure of Bleeding Tissue with Inhibited Postoperative Adhesion.

Most of the current bioadhesives cannot perform well on bleeding tissues while postoperative adhesion is a general but serious clinical issue. Here, a three-layer biodegradable Janus tissue patch (J-TP) that is able to simultaneously enable efficient closure of bleeding wounds with significantly promoted clotting ability and suppressed postoperative adhesion of tissues is reported. A dry adhesive hydrogel bottom layer of the J-TP can form rapid (within 15 s) and strong (tensile strength up to 98kPa) adhesion to bleeding/wet tissues with high bursting pressure (about 312.5mmHg on a sealed porcine skin) through hydrogen binding and covalent conjugation between the carboxyl & N-hydroxy succinimide (NHS) groups of hydrogel and the primary amine groups of tissues, while the phosphonic motifs can significantly reduce blood loss (by 81% on a rat bleeding liver model) of bleeding wounds. A thin polylactic acid (PLA) middle layer can improve the tensile strength (by 132%) of the J-TP in wet conditions while the grafted zwitterionic polymers can effectively prevent postoperative tissue adhesion and inflammatory reaction. This J-TP may be a promising tissue patch to assist the clinical treatment of injured bleeding tissues with inhibited postoperative adhesion.

Improving Effects of Peripheral Nerve Decompression Microsurgery of Lower Limbs in Patients with Diabetic Peripheral Neuropathy

Peripheral nerve decompression microsurgery can relieve nerve entrapment and improve the symptoms of DPN. However, postoperative tissue adhesion will produce new pressure on the nerves, affecting the surgical efficacy. In this study, a nerve conduit was used in the peripheral nerve decompression microsurgery to prevent postoperative adhesions, and the role of the nerve conduit in surgical nerve decompression was explored. A total of 69 patients with DPN were recruited and randomly divided into three groups: the nerve conduit group, conventional surgery group, and control group. Two weeks before surgery and 6 months after surgery, patients in each group were clinically tested using the visual analog scale (VAS) score, neurophysiological test, Toronto clinical scoring system (TCSS) score, and two-point discrimination (2-PD) test. The patients' symptoms in the nerve conduit group were relieved to varying degrees, and the relief rate reached 90.9%; the treatment efficacy was higher than that in the other groups. The postoperative nerve conduction velocity (NCV) in the two surgical groups was significantly higher than that before the surgery, and the difference between the nerve conduit group and the conventional surgery group was statistically significant (p < 0.05). For the 2-PD test, there was a statistically significant difference between the two surgical groups (p < 0.05). The TCSS score in the two surgical groups was significantly higher than that in the control group (p < 0.01). There was a significant difference in the TCSS scores between the nerve conduit group and the conventional surgery group (p < 0.05). The nerve conduit could further improve the efficacy of peripheral nerve decompression microsurgery in the treatment of DPN.

Salt sensitive purely zwitterionic physical hydrogel for prevention of postoperative tissue adhesion.

Abdominal adhesions are a class of serious complications following abdominal surgery, resulting in a complicated and severe syndrome and sometimes leading to a Gordian knot. Traditional therapies employ hydrogels synthesized using complicated chemical formulations-often with click chemistry or thermal responsive hydrogel. The complicated synthesis process and severe conditions limit the extent of the hydrogels' applications. In this work, poly 3-[2-(methacryloyloxy)ethyl](dimethyl)-ammonio]-1-propanesulfonate (PSBMA) polymer was synthesized to self-assemble into physical hydrogels due to the inter- and intramolecular ion interactions. The strong static interaction bonding density has a substantial impact on the gelation and physicochemical properties, which is beneficial to clinical applications and offers a novel way to obtain the desired hydrogel for a specific biomedical application. Intriguingly, this PSBMA polymer can be customized into a transient network with outstanding antifouling capability depending on the ion concentration. As ion concentration increases, the PSBMA hydrogel dissociated completely, endowing it as a candidate for adhesion prevention. In the cecum-sidewall model, the PSBMA hydrogel demonstrated superior anti-adhesion properties than commercial HA hydrogel. Furthermore, we have demonstrated that this PSBMA hydrogel could inhibit the inflammatory response and encourage anti-fibrosis resulting in adhesion prevention. Most surprisingly, the recovered skins of cecum and sidewall are as smooth as the control skin without any scar and damage. In conclusion, a practical hydrogel was synthesized using a facile method based on purely zwitterionic materials, and this ion-sensitive, antifouling adjustable supramolecular hydrogel with great clinic transform potential is a promising barrier for preventing postoperative tissue adhesion. STATEMENT OF SIGNIFICANCE: The development of hydrogels with satisfactory coverage, long retention time, facile synthetic method, and good biocompatibility is vital for preventing peritoneal adhesions. Herein, we developed a salt sensitive purely zwitterionic physical hydrogel poly 3-[2-(methacryloyloxy)ethyl](dimethyl)-ammonio]-1-propanesulfonate (PSBMA) hydrogel to effectively prevent postoperative and recurrent abdominal adhesions. The hydrogel was simple to synthesize and easy to use. In the cecum-sidewall model, PSBMA hydrogel could instantaneously adhere and fix on irregular surfaces and stay in the wound for more than 10 days. The PSBMA hydrogel could inhibit the inflammatory response, encourage anti-fibrosis, and restore smoothness to damaged surfaces resulting in adhesion prevention. Overall, the PSBMA hydrogel is a promising candidate for the next generation of anti-adhesion materials to meet clinical needs.

Zwitterionic biodegradable physical hydrogel based on ATRP technology for effective prevention of postoperative tissue adhesion

Postoperative adhesions are one of the most common complications post intraperitoneal surgery. Even after the adhesiolysis, the recurrence of adhesions is as high as 85%. Although zwitterionic-based materials have been reported for the application, unlike the conventional zwitterionic hydrogel, a series of poly (sulfobetaine methacrylate) grafted dextran derivatives (Dex-g-PSBMA) were synthesized by atom transfer radical polymerization (ATRP) reaction, making it fined controllable copolymer by its living polymerization property. Intriguingly, the Dex-g-PSBMA copolymer can self-assemble into a physical hydrogel under physiological conditions. When injected at the site of the lesions, it can immediately cover the wound area, and as the ion concentration increases, the chemical bonds dissociate and the hydrogel may degrade completely. In the abdominal wall-cecum injury adhesion model in rats, Dex-g-PSBMA hydrogel showed excellent anti-adhesion ability, effectively preventing postoperative abdominal wall-cecum adhesion. The mechanism exploration revealed that Dex-g-PSBMA hydrogel can take an effect on the TGF-β/Smad signaling pathway, which can inhibit the Smad3 and activate the Smad7 pathway, thereby reducing the probability of tissue fibrosis, reducing fibrin deposition, and resisting fibroblast adhesions. In conclusion, these findings demonstrated that this Dex-g-PSBMA physical hydrogel is a promising candidate for completely preventing post-surgical adhesions.

Injectable adhesive self-healing biocompatible hydrogel for haemostasis, wound healing, and postoperative tissue adhesion prevention in nephron-sparing surgery

Nephron-sparing surgery is a well-established treatment in patients with T1a renal cell carcinoma; however, the complex suturing process prolongs warm ischaemia time, affects the preservation of normal renal parenchymal function, and causes avoidable postoperative tissue adhesion complications, including chronic abdominal pain, intestinal obstruction, and female infertility. Hence, the design of multifunctional biomaterials with haemostasis, postoperative wound management, and postoperative tissue adhesion prevention properties for nephron-sparing surgeries is urgently needed. In this study, a series of injectable adhesive multifunctional biocompatible hydrogels were designed based on the free-radical polymerisation of monomers acryloyl-6-aminocaproic acid (AA) and N-acryloyl 2-glycine (NAG), and the ionic coordination between Ca2+ and the abundant carboxyl groups in AA and NAG. AA/NAG/Ca (AA, NAG, and Ca refer to acryloyl-6-aminocaproic acid, N-acryloyl 2-glycine and calcium chloride, respectively) hydrogel exhibited good mechanical properties, swelling and adhesion properties, flexibility, in vitro blood-clotting ability, and cytocompatibility. In vivo experiments on liver injury models and rat/rabbit nephron-sparing surgery models elucidated that the AA/NAG/Ca hydrogel had haemostasis performance and wound healing properties that led to short bleeding time, reduced bleeding volume, and well-organised nephron structures. An abdomen-caecum adhesion model indicated that the AA/NAG/Ca hydrogel showed excellent anti-adhesion properties. In summary, this multifunctional hydrogel exhibited potential for improving haemostasis and wound management in nephron-sparing surgeries, showing potential for clinical application. Statement of significanceExtended warm ischemia time during nephron sparing surgery negatively affected postoperative renal function due to the need for hemostasis at the wound with abundant blood supply, and postoperative wound healing and additional adhesions caused by the surgical procedure deserve attention. Based on the efficient and stable adhesion properties of hydrogels and the ability to promote wound healing. Herein, a series of adhesive self-healing biocompatible hydrogels were prepared based on free-radical polymerization of acryloyl-6-aminocaproic acid (AA) and N-acryloyl 2-glycine (NAG) and the ionic coordination between Ca2+ with the abundant carboxyl groups in AA and NAG. AA/NAG/Ca hydrogel showed hemostasis property in nephron sparing surgery model, promote kidney wound healing, and could perform anti-postoperative adhesion efficacy in an abdomen-caecum adhesion model.

A combination of hybrid polydopamine-human keratinocyte growth factor nanoparticles and sodium hyaluronate for the efficient prevention of postoperative abdominal adhesion formation

Postoperative abdominal adhesion (PAA) is one of the more universal complications of abdominal surgery with a frequent incidence. Currently available keratinocyte growth factor (KGF)-based glues for the prevention of adhesions remain a great bottleneck since their long-term biological activity in vivo is insufficient. In this study, we fabricated hybrid polydopamine (PDA)-KGF nanoparticles (PDA-KGF NPs) by using an in situ self-assembly and polymerization method. The physicochemical properties of the PDA-KGF nanoparticles were systematically characterized. The effect of preventing PAA in rats was evaluated by using hybrid PDA-KGF NPs combined with hyaluronate (Ha). The expression levels of inflammatory factors and the degree of inflammatory cell infiltration in the injured peritoneum were evaluated by enzyme-linked immunosorbent assays and hematoxylin-eosin staining, respectively. The levels of phospho-Src expression were revealed by Western blotting. The degree of fibrosis and the density of deposited collagen fibers were measured with real-time reverse-transcription polymerase chain reaction and picrosirius red staining. The results indicated that the PDA-KGF NPs combined with Ha greatly prevented the incidence of abdominal adhesion s and promoted the repair of mesothelial cells in injured peritoneum. More importantly, the PDA-KGF NPs combined with Ha obviously reduced collagen deposition and fibrosis and inhibited the inflammatory response. Our results suggest that PDA-KGF NPs combined with Ha are promising barrier-like biomaterials for the effective prevention of postoperative tissue adhesion. Statement of significancePostoperative abdominal adhesion (PAA) as an inevitable postoperative complication affected the quality of life of patients. Currently available methods for preventing adhesions mainly employ degradable biomaterials. Previous research demonstrated that a hybrid keratinocyte growth factor (KGF)-sodium hyaluronate (Ha) gel could prevent the formation of PAAs. However, its clinical outcomes are not satisfactory since their bioactivity in vivo is too short. In this article, we fabricated hybrid polydopamine (PDA)-KGF nanoparticles (PDA-KGF NPs), which extend KGF bioactivity, effectively prevent PAA. Moreover, PDA-KGF NPs could remarkably reduce both collagen deposition and fibrosis, inhibit the inflammatory response, and promote mesothelial regeneration. Overall, the PDA-KGF NPs combined with Ha exhibit efficient antiadhesion properties, may provide a promising clinical protocol for the prevention of PAA.

Assessment of Antimicrobial Agents, Analgesics, and Epidermal Growth Factors-Embedded Anti-Adhesive Poly(Lactic-Co-Glycolic Acid) Nanofibrous Membranes: In vitro and in vivo Studies.

BackgroundPostoperative tissue adhesion is a major concern for most surgeons and is a nearly unpreventable complication after abdominal or pelvic surgeries. This study explored the use of sandwich-structured antimicrobial agents, analgesics, and human epidermal growth factor (hEGF)-incorporated anti-adhesive poly(lactic-co-glycolic acid) nanofibrous membranes for surgical wounds.Materials and MethodsElectrospinning and co-axial electrospinning techniques were utilized in fabricating the membranes. After spinning, the properties of the prepared membranes were assessed. Additionally, high-performance liquid chromatography and enzyme-linked immunosorbent assays were utilized in assessing the in vitro and in vivo liberation profiles of the pharmaceuticals and the hEGF from the membranes.ResultsThe measured data suggest that the degradable anti-adhesive membranes discharged high levels of vancomycin/ceftazidime, ketorolac, and hEGF in vitro for more than 30, 24, and 27 days, respectively. The in vivo assessment in a rat laparotomy model indicated no adhesion in the peritoneal cavity at 14 days post-operation, demonstrating the anti-adhesive capability of the sandwich-structured nanofibrous membranes. The nanofibers also released effective levels of vancomycin, ceftazidime, and ketorolac for more than 28 days in vivo. Histological examination revealed no adverse effects.ConclusionThe outcomes of this study implied that the anti-adhesive nanofibers with sustained release of antimicrobial agents, analgesics, and growth factors might offer postoperative pain relief and infection control, as well as promote postoperative healing of surgical wounds.

An Ultrasoft Self-Fused Supramolecular Polymer Hydrogel for Completely Preventing Postoperative Tissue Adhesion.

The intermolecular H-bonding density heavily influences the gelation and rheological behavior of hydrogen-bonded supramolecular polymer hydrogels, thus offering a delicate pathway to tailor their physicochemical properties for meeting a specific biomedical application. Herein, one methylene spacer between two amides in the side chain of N-acryloyl glycinamide (NAGA) is introduced to generate a variant monomer, N-acryloyl alaninamide (NAAA). Polymerization of NAAA in aqueous solution affords an unprecedented ultrasoft and highly swollen supramolecular polymer hydrogel due to weakened H-bonds caused by an extra methylene spacer, which is verified by variable-temperature Fourier transform infrared (FTIR) spectroscopy and simulation calculation. Intriguingly, poly(N-acryloyl alaninamide) (PNAAA) hydrogel can be tuned to form a transient network with a self-fused and excellent antifouling capability that results from the weakened dual amide H-bonding interactions and enhanced water-amide H-bonding interactions. This self-fused PNAAA hydrogel can completely inhibit postoperative abdominal adhesion and recurrent adhesion after adhesiolysis in vivo. This transient hydrogel network allows for its disintegration and excretion from the body. The molecular mechanism studies reveal the signal pathway of PNAAA hydrogel in inhibiting inflammatory response and regulating fibrinolytic system balance. This self-fused, antifouling ultrasoft supramolecular hydrogel is promising as a barrier biomaterial for completely preventing postoperative tissue adhesion.

Tetramethylpyrazine Improves Postoperative Tissue Adhesion: A Drug Repurposing.

Plants are known to possess plenty of pharmacological activities as a result of various phytoconstituents. Tetramethylpyrazine (TMP), one of the most widely used medicinal compound isolated from traditional Chinese herb, is usually employed for anti-oxidation, anti-inflammation, anti-platelet aggregation, anti-lipid, anti-fibrosis, as well as activating blood, removing stasis, dilating small arteries, improving microcirculation and antagonizing calcium. In the present paper, the anti-adhesion effect of TMP were reviewed. TMP was found to play a multi-target and muti-link role in anti-adhesion by inhibiting hyperplasia of collagen and overexpression of adhesion-related factors and reducing the concentration of white blood cells and fibrin in plasma. Because previous studies mostly focused on in vitro experiments and animal experiments, there is an urgent need for clinical research with abundant indicators to further prove its anti-adhesion potency. Future basic research should concentrate on the development of TMP as a biological material.