Aldehyde Functionalised Chitosan-based Novel Biomaterials for Addressing Biomedical Challenges

Infections including wound infections and implant-associated infections, ocular drug delivery, and chronic tunnelling wounds, present significant challenges to the biomedical field. These challenges greatly reduce the quality of life and increase the economic burden for patients. Current strategies rely on antibiotics for infection control, eye drops for ophthalmic drug delivery, and wound dressings combined with drugs for chronic tunnelling wound healing. Although these methods showed effectiveness, there are still some limitations such as the potential adverse effects, emergence of antibiotic-resistant microbes, frequent administration, and low bioavailability. Therefore, there is an urgent need to design advanced biomaterials using naturally derived polymers to address current challenges more effectively and precisely. Chitosan (CTS) has been widely used in the biomedical field due to its ability to promote wound healing, antibacterial properties, biocompatibility, and biodegradability. However, the application of toxic or costly crosslinkers, rapid degradation, and poor solubility still need to be addressed. We synthesized an aldehyde-functionalized chitosan (CTS-CHO) through a controllable oxidization reaction. Aldehyde groups in its structure are able to crosslink with other amino-containing polymers through Schiff base reaction but without chemical crosslinkers. After crosslinking, the degradation duration and mechanical properties of biomaterials will be highly improved. Besides the crosslinking ability, CTS-CHO shows antimicrobial activity and good solubility, making it a promising bio-crosslinker. Here, we designed and fabricated four biomaterial systems using CTS-CHO, aiming to address the abovementioned issues. Firstly, the hydrogel designed for the treatment of wound infections was prepared by crosslinking CTS with CTS-CHO, which showed injectability, self-healable properties, and antibacterial activity. Secondly, CTS-CHO was used to form an antibacterial coating on the polylactic acid (PLA) surface by layer-by-layer (LbL) technology. The transparency, biocompatibility, and antibacterial activities presented the coating as a promising candidate for controlling implant-related infections. Thirdly, the hydrogel designed for ocular drug delivery was fabricated with CTS-CHO by adjusting its concentrations. The slow drug release ability and injectability show promise in treating dry eye disease (DED) and diabetic retinopathy (DR) through topical application and intravitreal injection, respectively. Finally, the fillable scaffold composed of collagen (COL) and CTS-CHO can promote cell proliferation obviously, inactivate overexpressed matrix metalloproteinases (MMPs), absorb exudate, and fill chronic tunnelling wounds effectively.