A suture-free, shape self-adaptive and bioactive PEG-Lysozyme implant for Corneal stroma defect repair and rapid vision restoration.

Corneal transplantation is a prevailing treatment to repair injured cornea and restore vision but faces the limitation of donor tissue shortage clinically. In addition, suturing-needed transplantation potentially causes postoperative complications. Herein, we design a PEG-Lysozyme injective hydrogel as a suture-free, shape self-adaptive, bioactive implant for corneal stroma defect repair. This implant experiences a sol-gel phase transition via an in situ amidation reaction between 4-arm-PEG-NHS and lysozyme. The physicochemical properties of PEG-Lysozyme can be tuned by the components ratio, which confers the implant mimetic corneal modulus and provides tissue adhesion to endure increased intraocular pressure. In vitro tests prove that the implant is beneficial to Human corneal epithelial cells growth and migration due to the bioactivity of lysozyme. Rabbit lamellar keratoplasty experiment demonstrates that the hydrogel can be filled into defect to form a shape-adaptive implant adhered to native stroma. The implant promotes epithelialization and stroma integrity, recovering the topology of injured cornea to normal. A newly established animal forging behavior test prove a rapid visual restoration of rabbits when use implant in a suture free manner. In general, this work provides a promising preclinical practice by applicating a self-curing, shape self-adaptive and bioactive PEG-Lysozyme implant for suture-free stroma repair.

Glucose and MMP-9 dual-responsive hydrogel with temperature sensitive self-adaptive shape and controlled drug release accelerates diabetic wound healing.

Chronic diabetic wounds are an important healthcare challenge. High concentration glucose, high level of matrix metalloproteinase-9 (MMP-9), and long-term inflammation constitute the special wound environment of diabetic wounds. Tissue necrosis aggravates the formation of irregular wounds. All the above factors hinder the healing of chronic diabetic wounds. To solve these issues, a glucose and MMP-9 dual-response temperature-sensitive shape self-adaptive hydrogel (CBP/GMs@Cel&INS) was designed and constructed with polyvinyl alcohol (PVA) and chitosan grafted with phenylboric acid (CS-BA) by encapsulating insulin (INS) and gelatin microspheres containing celecoxib (GMs@Cel). Temperature-sensitive self-adaptive CBP/GMs@Cel&INS provides a new way to balance the fluid-like mobility (self-adapt to deep wounds quickly, approximately 37 °C) and solid-like elasticity (protect wounds against external forces, approximately 25 °C) of self-adaptive hydrogels, while simultaneously releasing insulin and celecoxib on-demand in the environment of high-level glucose and MMP-9. Moreover, CBP/GMs@Cel&INS exhibits remodeling and self-healing properties, enhanced adhesion strength (39.65 ± 6.58 kPa), down-regulates MMP-9, and promotes cell proliferation, migration, and glucose consumption. In diabetic full-thickness skin defect models, CBP/GMs@Cel&INS significantly alleviates inflammation and regulates the local high-level glucose and MMP-9 in the wounds, and promotes wound healing effectively through the synergistic effect of temperature-sensitive shape-adaptive character and the dual-responsive system.