Mucosal Cell Composites Using Human Dermal Matrix
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Solution Overview
Problem
Current methods for developing mucosal cell composites for trauma and disease treatment are limited by the use of unsuitable skin techniques, fragility of cultured epithelial sheets, reliance on irradiated mouse fibroblasts, and the presence of xenogeneic agents in cell culture media, which pose safety risks and inefficiencies in delivery and bioavailability of therapeutic agents.
Innovation Solution
The development of mucosal cell composites comprising a layer of epithelial cells cultured with a substantially non-immunogenic human dermal matrix in a serum-free culture medium, enhanced with biological agents introduced into the epithelial cells, allowing for improved handling, integration, and targeted delivery of therapeutic agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If cultured sheets of epithelial cells are used for mucosal reconstruction, then the need for second surgical procedures is eliminated, but the sheets become fragile and difficult to handle
Solution Approach 1:
The patent combines cultured epithelial cells with a dermal matrix scaffold to create a composite tissue construct. This composite structure provides mechanical support that eliminates the fragility of standalone epithelial sheets, enabling safe handling and transplantation as a single unit without requiring secondary surgical procedures.
Solution Approach 2:
The dermal matrix acts as an intermediary substrate that supports the epithelial cells during culture and transplantation. This intermediary structure provides the necessary mechanical strength for handling while biodegrading over time to allow integration with host tissue, resolving the handling difficulty without compromising the elimination of second procedures.
2Productivity
If irradiated mouse fibroblasts are used as feeder layer for cell culture, then cell proliferation is enhanced, but the risk of murine DNA contamination increases
Solution Approach 1:
The patent removes the xenogeneic feeder layer component from the culture system entirely. Instead of using irradiated mouse fibroblasts, the invention employs a defined serum-free medium with human-derived growth factors and a human dermal matrix scaffold, thereby eliminating the source of murine DNA contamination while maintaining cell proliferation through alternative mechanisms.
Solution Approach 2:
The patent changes the cultural parameters from serum-containing media with xenogeneic feeders to defined serum-free media with human growth factors. This parameter change eliminates contamination risks while maintaining productivity through controlled delivery of essential growth factors like EGF and FGF from the human dermal matrix.
3Productivity
If FBS and BPE are used in cell culture medium, then cell growth is supported, but the risk of xenogeneic agent introduction increases
Solution Approach 1:
The patent extracts and removes FBS and BPE from the culture medium, replacing them with a defined serum-free formulation containing only human-derived growth factors and nutrients. This elimination of animal-derived products removes the pathway for xenogeneic agent introduction while maintaining cell growth support through recombinant human growth factors.
Solution Approach 2:
The patent fundamentally changes the medium composition parameters from undefined serum-based media to defined serum-free media with specified concentrations of human growth factors. This parameter change enables controlled cell growth without xenogeneic contamination risks inherent in FBS and BPE.
4Strength
If collagen gel is added to cultured epithelial cells to form composite, then structural support is improved, but fragility and handling difficulty persist in oral cavity environment
Solution Approach 1:
The patent uses human dermal matrix as the structural scaffold instead of collagen gel. This dermal matrix provides superior mechanical strength and handling properties specifically suited for the oral cavity environment, while being resistant to degradation by oral collagenolytic enzymes. The composite structure integrates epithelial cells with this robust dermal framework for easy manipulation and transplantation.
Solution Approach 2:
The patent changes the matrix material parameter from collagen gel to human dermal matrix, which has different biochemical and mechanical properties. This dermal matrix resists degradation by oral collagenases and provides enhanced structural integrity, transforming the composite from fragile to handleable in the challenging oral cavity environment.
Data Source
AI summary
The present invention discloses a composite made of a layer of epithelial cells cultured together with a dermal matrix in a culture medium, which is free of BPE. The dermal matrix is a substantially non-immunogenic human dermis. Also disclosed is an enhanced composite where a biological agent has been introduced into the epithelial cells. The invention also comprises methods of making and implanting both the composite and the enhanced composite in an animal. A method of treating disease or injury through the use of the disclosed composites is also part of the present invention.