Hydrogel-assisted tissue repair and surgical reconstruction in urogenital diseases

Functional Hydrogels for Minimally Invasive Urological Therapy:

Targeted Repair of Hemorrhagic Cystitis and Vas Deferens Recanalization

This study focuses on the key clinical challenges in urological diseases and develops a series of functional and biodegradable hydrogel biomaterials for targeted tissue repair and minimally invasive treatment.

Aiming at the treatment dilemma of hemorrhagic cystitis (HC) caused by the dynamic urinary environment, cyclic mechanical stress, fragile mucosal damage and persistent inflammation, two types of bladder-adaptive bioadhesive hydrogels were constructed in this work.

First, tea polyphenols (TP) were introduced into photo-crosslinked silk fibroin methacryloyl network to fabricate SFMA/TP composite hydrogels. Relying on strong hydrogen bonding and tissue affinity of TP, the hydrogel achieved robust under-urine adhesion and excellent mechanical tolerance, with an adhesive strength of 15.1 kPa to adapt to the cyclic contraction of the bladder. It also exhibited urea-responsive degradation behavior and good in vitro and in vivo biodegradability. In the cyclophosphamide-induced HC rat model, the SFMA/TP hydrogel realized efficient hemostasis, relieved local inflammation, promoted angiogenesis and smooth muscle regeneration, and significantly accelerated bladder mucosal repair.

Second, a supramolecular gelatin-based adhesive hydrogel (HGCQ) was designed for long-term local treatment of HC. Combined with acrylated β-cyclodextrin and dopamine-functionalized hyaluronic acid, the HGCQ hydrogel achieved sustained and linear quercetin release for up to 48 h, outstanding bladder burst pressure resistance of 18.8 kPa, and rapid hemostatic performance. It possessed excellent ROS scavenging capacity, broad-spectrum antibacterial property and anti-inflammatory effects by regulating the NF-κB/IL-17 signaling pathway. In vivo experiments verified that HGCQ could reconstruct the urothelial barrier, increase collagen III deposition and inhibit inflammatory progression, which is of great value for HC intervention.

In addition, targeting postoperative complications including low anastomotic efficiency, poor healing and anastomotic stenosis after vasovasostomy, we constructed a coaxial-printable and robust PCB hydrogel stent. Based on host-guest complexation and degradable crosslinking structure, the PCB hydrogel displayed superior mechanical performance. In rabbit microsurgical models, the hydrogel stent shortened the tissue anastomosis time by more than half. Benefiting from its cell anti-adhesion property and complete degradation within 28 days in vivo, the stent effectively prevented vas deferens stenosis and achieved a 100% long-term patency rate.

In summary, through rational molecular design and functional optimization, the developed multifunctional hydrogels perfectly adapt to complex physiological microenvironments. This series of research provides novel and effective minimally invasive therapeutic options for hemorrhagic cystitis and vas deferens reconstruction, and offers new references for the development of advanced functional biomaterials in regenerative medicine.

Speaker

Dr. Kerong Wu - The First Affiliated Hospital of Ningbo University (China).