Structural Bionic And Functionalized Hydrogel For Penile Defect Repair

As an important reproductive and sexual organ in men,the penis can be exposed to a wide range of health threats.For penile defects caused by trauma and surgical treatment,or degenerative lesions and erectile dysfunction caused by chronic diseases and aging,ideal treatment options are still lacking in clinical practice.From a tissue engineering perspective,the penis is both a terminally differentiated organ and a highly dynamic organ,requiring specific design of biomaterials to achieve diverse biological adaptations and ultimately good therapeutic outcomes.In this study,the hydrogels were designed in terms of biocompatibility,mechanical properties,macro/microstructure and physiological functions,and processed into the desired shape and size by 3D printing and other methods.The effects of different raw material formulations and processing conditions on 3D printing effects,biocompatibility,haemocompatibility,microstructure and mechanical properties were investigated.The constructed tissue-engineered scaffolds can be used for repair or replacement of cavernosal and tunica albuginea defects in the male penis.This study focuses on patients with common penile corpus cavernosum defects and leukodystrophy in reproductive surgery as follows.(1)Design and preparation of bionic artificial tunica albugineaIn this part,the microstructure of tunica albuginea was thoroughly analysed and discussed,and a two-layer bionic artificial tunica albuginea similar to the structure of natural tunica albuginea was constructed by using synthetic polymer materials combined with mechanical stretching to induce fibre orientation.The bionic artificial tunica albuginea has a J-shaped stress-strain curve similar to that of natural tunica albuginea,while having high burst pressure,good suturing performance and excellent anti-platelet adhesion effect.Through finite element simulation analysis,we simulated and analysed the stresses of tunica albuginea with different fibre arrangements,and proved that the arrangement structure of natural tunica albuginea has its unique advantages.The artificial tunica albuginea material showed immediate and long-term repair effects in the experiments of repairing tunica albuginea defects in Bama pigs.(2)Study of 3D printing ink based on small molecule diffusion-induced phase separationIn this part,a range of 3D printing inks based on small-molecule diffusion-induced phase separation was prepared by introducing a small-molecule hydrogen bond disruptor urea into hydrogen bond cross-linked hydrogels,which can be cured rapidly in response to the external environment.The 3D printing ink system is suitable for a variety of synthetic or natural sources of hydrogen-bonded cross-linked hydrogels with mild printing conditions and fast curing speed,and the resulting scaffolds have good biocompatibility and can be used for cell 3D culture.The scaffolds also have typical antibacterial and antioxidant effects,and have a large potential for application in the field of tissue repair.(3)Design and construction of functionalized tunica albuginea-corpus cavernosum scaffoldThis part was assembled into an integrated tunica albuginea-corpus cavernosum scaffold based on the hydrogen-bonded cross-linked 3D printed scaffold and the microstructured bionic artificial tunica albuginea constructed in the previous stage.The structure of the 3D printed scaffold was optimised according to the microstructure and physiological function of the penis,and the mechanical adaptation of the scaffold to the dynamic process of penile erection weakness was achieved by introducing a negative Poisson’s ratio design.Furthermore,based on the important role of nitric oxide in penile erection and vascular regeneration,a surfacemodified layer that catalyses endogenous nitric oxide donors in the blood was designed on the surface of the cavernous repair scaffold to achieve pro-vascularisation,pro-endothelialisation and inhibition of excessive smooth muscle cell proliferation.Based on the artificial tunica albuginea,rockulose was further introduced to achieve tight bonding with PVA through chemical crosslinking,and it can stably exert the effect of promoting endothelialisation and preventing thrombus adhesion for a long time.(4)Functionalized tunica albuginea-corpus cavernosum scaffold for repairing large penile defectsAs the regeneration of the vascular network and endothelialisation are critical to the efficacy of penile cavernous tissue repair,this study was conducted in a rabbit model of large penile segmental defect associated with in situ tissue repair based on a cavernous tunica albuginea repair scaffold with a catalytic endogenous nitric oxide production coating developed in the previous paper.The scaffold material worked in concert with the functionalised coating to achieve good repair of cavernous function and restore normal erectile morphology and ejaculatory function in male rabbits.This work has great potential for use in male patients with penile injuries.In conclusion,based on the design concept of biological adaptability,this study designed and constructed mechanically and functionally adapted cavernous repair scaffolds with artificial tunica albuginea materials for the cellular composition,physiological function and microstructure of penile tissues through 3D printing,mechanical exercise and other preparation methods combined with functionalised modification techniques.Through the characterisation of the basic properties of the materials,in vitro cellular experiments and in vivo animal experiments,we initially verified their efficacy as tissue engineering scaffold materials for the repair of cavernous and tunica albuginea defects,providing new options and guidance for further research and potential clinical applications.