Construction Of Hydrophilic/Hydrophobic Janus Polymer Composite Membranes And Their Application In Dural Defects

Dural defects,caused by external trauma,surgery,or tumor invasion,are common problems that can lead to a range of complications,including cerebrospinal fluid leakage,low intracranial pressure syndrome,and intracranial infection.To prevent the occurrence of these complications,it is necessary to find appropriate and effective treatment methods.Currently,the main clinical treatments include watertight suture closure,non-penetrating titanium clip closure,use of biological adhesives,and other adjunctive therapies.However,these methods can not be used alone for patients with large dural defects,and must be combined with grafts and patches for treatment.However,there are some drawbacks to current clinical practices and the development of grafts and patches,such as too fast or no degradation,severe swelling,lack of bioactivity,insufficient mechanical strength,poor biocompatibility,the need for additional incision material,limited sources,and weak interactions between multi-layer material layers.Therefore,the preparation of a biodegradable,safe,effective,widely available,easy-to-prepare,and biologically functional Janus membrane with tight interlayer binding is currently a hot topic in the treatment of dural defects,especially in anterior skull base reconstruction.In order to meet these requirements,this study utilized directional freezing-salt leaching-thermal annealing and electrospinning techniques to prepare two types of Janus polymer composite membranes with hydrophilic/hydrophobic properties,known as Janus membranes.The main research content of this paper is as follows:(1)The hydrophilic/hydrophobic Janus membrane based on polyvinyl alcohol hydrogel for dural defect repair was prepared.Firstly,a polyvinyl alcohol hydrogel membrane was prepared using the directional freezing-salt leaching method,and then annealed and coated with a hydrophobic layer to form a Janus structure hydrogel membrane with one hydrophilic and one hydrophobic side.Through thermal gravimetric analysis and differential scanning calorimetry characterization,it was demonstrated that this hydrogel Janus membrane has good thermal stability below 200 ℃,and annealing treatment can increase the crystallinity of the polyvinyl alcohol hydrogel to 29.30% ± 2.47%.In addition,scanning electron microscopy and tensile testing showed that freezing-salt leaching-thermal annealing treatment can form micro and nano-level networks within the hydrogel,significantly enhancing and solidifying its mechanical strength to 8.93 ± 1.46 MPa,higher than that of natural dura mater.The scanning electron microscopy,contact angle measurement,and in vitro degradation experiment verified the asymmetrical structure and hydrophilic/hydrophobic properties of the Janus hydrogel membrane,and demonstrated tight interlayer binding,slow biodegradability,and good resistance to swelling.Furthermore,cell counting kit-8 assay,live/dead staining,subcutaneous implantation,and dural defect rat model experiments confirmed the good biocompatibility of the Janus hydrogel membrane with cells,tissues,and organs,and its effectiveness in preventing brain tissue adhesion and cerebrospinal fluid leakage.However,the results also indicated that the mechanical strength of the Janus hydrogel membrane is significantly different from that of surrounding tissues,which may lead to severe inflammatory reactions and fibrous encapsulation,which is not conducive to subsequent dural repair.Overall,this study confirms the effectiveness of the Janus structure in the treatment of dural defects,and the universal method for preparing this hydrogel membrane holds promise for application in the repair and replacement of tissues such as cartilage and tendons.(2)A high-adhesion/hydrophobic left-handed polylactic acid(L-PLA)Janus membrane loaded with growth peptides was prepared using electrospinning technology for repairing dural defects.The peptide-modified Janus membrane,made of biocompatible L-PLA,was prepared by co-electrospinning with modified copper peptides(GKF),followed by acetone treatment and addition of a polydopamine coating.Mass spectrometry and transmission electron microscopy confirmed the successful synthesis of the peptide,which could self-assemble into nanofibers in water solution.CCK-8 assays demonstrated that GKF peptides can promote cell proliferation.The dopamine coating of the peptide-modified Janus membrane was successfully applied,and tensile testing and scanning electron microscopy confirmed that the peptide-modified Janus membrane had a tensile strength of 3.57 MPa and a fracture strain of 68%,similar to that of the natural dura mater.Droplet permeation experiments and contact angle measurements showed that the peptide-modified Janus membrane had good water tightness and two-sided wetting asymmetry.In vitro degradation and subcutaneous implantation experiments demonstrated the slow degradation and peptide-release ability of the peptide-modified Janus membrane.CCK-8 assays,subcutaneous implantation,and a rat dural defect model confirmed the good biocompatibility of the peptide-modified Janus membrane and its ability to prevent cerebrospinal fluid leakage,anti-adhesion,and promote dura mater repair.Further experiments suggested that GKF peptides may promote dura mater regeneration by promoting fibroblast proliferation,but their molecular mechanism still needs further investigation.