Ndrg2 Knockout Dendritic Cells in Hydrogel for Wound Healing
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Solution Overview
Problem
Current treatments for chronic wounds, such as skin grafting and tissue engineered skin substitutes, are invasive and often ineffective, especially in patients with diabetes and peripheral vascular disease, due to impaired angiogenesis and healing responses.
Innovation Solution
The use of edited dendritic cells (DCs) genetically modified to downregulate N-myc downregulated gene 2 (Ndrg2) expression, applied in a hydrogel scaffold to enhance wound healing by promoting angiogenesis and regenerative processes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If skin grafting or tissue engineered skin substitutes are used to treat chronic wounds, then wound coverage can be achieved, but the treatment requires surgical interventions and often fails in patients with diabetes and peripheral vascular disease due to impaired angiogenesis
Solution Approach 1:
The patent uses dendritic cells as intermediary agents that mediate wound healing through immunomodulation and angiogenesis promotion. These cells act as a biological mediator between the wound environment and the healing process, eliminating the need for direct surgical intervention while improving reliability in diabetic patients
Solution Approach 2:
The patent modifies dendritic cells through genetic engineering to alter their functional parameters, specifically enhancing their ability to promote angiogenesis and modulate immune responses. This parameter change enables the cells to effectively treat chronic wounds that would otherwise fail to heal
2Reliability
If mesenchymal stromal cells are used for cell-based therapy, then beneficial secretory and regenerative effects are achieved, but isolation requires tissue biopsies or surgical interventions and stem cell cultivation comes at significant costs
Solution Approach 1:
The patent extracts the therapeutic function of interest (immunomodulation and angiogenesis promotion) from complex stem cell systems and implements it using dendritic cells, which can be isolated through simpler leukapheresis procedures without requiring tissue biopsies or extensive cultivation
Solution Approach 2:
The patent employs dendritic cells that can be produced more economically and with simpler procedures compared to mesenchymal stromal cells. The cells are used in a single application context, providing cost-effective therapy without the need for long-term cultivation infrastructure
3Productivity
If conventional wound treatments are used, then standard care can be provided, but healing is significantly delayed in chronic wounds with impaired angiogenesis
Solution Approach 1:
The patent applies genetically modified dendritic cells that are pre-engineered to promote angiogenesis and immunomodulation before the wound healing process begins. This preliminary action of enhancing the biological environment accelerates subsequent healing, overcoming the time loss associated with impaired angiogenesis
Solution Approach 2:
The patent creates a composite therapeutic approach combining genetically modified dendritic cells with hydrogel delivery systems. This composite material delivers the cells effectively to the wound site while providing a controlled environment that enhances healing rate and reduces treatment time
Data Source
AI summary
The present disclosure provides compositions and methods for enhanced healing of wounds, e.g. cutaneous wounds, by application of a scaffold or matrix, e.g. a hydrogel, comprising an effective dose of edited dendritic cells (DCs). As used herein, edited dendritic cells refers to mammalian, usually human, dendritic cells that have been genetically modified to alter expression of one or more genes involved in wound healing. In some embodiments edited DC are modified to downregulate or substantially eliminate expression of N-myc downregulated gene 2 (Ndrg2) expression, which cells may be referred to as Ndrg2 KO DCs.