Biocompatible proteoliposome technology for enhanced wound healing and reduced inflammation in diabetic patients

Syndesomes—lipid vesicles with embedded syndecan-4 and PDGF-BB—enhance wound healing by promoting cellular activities, reducing inflammation, and improving tissue regeneration. They are particularly effective in diabetic and obese models, supporting re-epithelialization and angiogenesis.

Background

Chronic non-healing wounds, particularly prevalent among individuals with type-2 diabetes and peripheral arterial disease (PAD), present a significant medical challenge. The rising incidence of these conditions has led to an increased occurrence of diabetic ulcers, which are complex and costly to treat, often resulting in limb amputations. Current treatment strategies, including debridement, infection control, and surgical interventions, provide only temporary relief and frequently fail to achieve long-term healing. Previous attempts to enhance wound healing using growth factor proteins or genes have shown limited success in clinical trials, particularly for chronic or recurring wounds. This underscores the urgent need for innovative therapeutic approaches that can effectively promote wound healing and reduce the risk of complications in this growing patient population.

Technology description

The technology described involves advanced compositions for wound healing, utilizing specialized proteovesicles known as “syndesomes.” These syndesomes incorporate a syndecan polypeptide within a lipid vesicle, paired with a platelet-derived growth factor (PDGF) polypeptide. The syndecan polypeptide, a cell surface heparan sulfate proteoglycan, plays a crucial role in mediating interactions between growth factors and their receptors, essential for cellular signaling and wound healing. The syndesomes are delivered to target cells via flexible carriers like liposomes and can be encapsulated in biodegradable microcapsules or microbeads made from biocompatible hydrogels such as alginate. This design facilitates sustained release at the wound site, aiming to enhance wound healing by promoting cellular activities, reducing inflammation, and encouraging tissue regeneration.

This technology is differentiated by its novel approach to co-deliver a growth factor with its co-receptor, syndecan-4, which significantly enhances the effectiveness of PDGF-BB therapy in wound healing. The syndesomes not only improve keratinocyte migration and fibroblast invasion but also modulate macrophage phenotypes, promoting a healing environment.

The use of biodegradable microcapsules for sustained release ensures a continuous therapeutic effect, which is particularly beneficial in chronic wound conditions like diabetic ulcers. This method addresses the limitations of previous growth factor therapies by providing a more targeted and efficient delivery system, thereby improving healing outcomes in clinically relevant models.

Benefits

Enhanced wound healing by promoting cellular activities essential for tissue repair
Reduction of inflammation and promotion of tissue regeneration
Improved interaction between growth factors and their receptors for effective cellular signaling
Potential to minimize inflammatory immune response during wound healing
Sustained release of therapeutic agents at the wound site through biodegradable microcapsules or microbeads
Increased effectiveness of PDGF-BB growth factor therapy in diabetic and obese models
Flexibility in delivery through incorporation into liposomes for targeted application