Hydrogel matrix technology for accelerating tissue-engineered dermal and vascular formation

A tissue-engineered dermal equivalent uses a hydrogel matrix with two distinct layers and mesenchymal stem cells (MSCs). One layer promotes blood vessel cell formation, while the other encourages dermal fibroblast development, facilitating vascular and dermal tissue creation from a single stem cell source.

Background

Severe skin injuries, such as full-thickness burns and non-healing ulcers, necessitate effective skin grafts to close wounds and protect underlying tissues. Traditional grafts, including autografts and allografts, often involve significant limitations such as donor site morbidity, limited availability, and potential immune rejection.

Tissue-engineered skin substitutes have emerged as a promising solution, yet they face considerable challenges. Early products like cultured epidermal autografts (CEAs) are fragile, infection-prone, and lack a dermal layer, limiting their utility. Composite skin substitutes combining dermal and epidermal layers have shown promise but are hindered by complex, lengthy culture processes and the need for sequential layering to achieve functional integration. Additionally, these substitutes must support vascularization to ensure graft viability and integration, a requirement that current methods struggle to meet efficiently. Thus, there is a critical need for innovative approaches that can simplify the production process, enhance structural integrity, and promote vascularization in engineered dermal equivalents.

Technology description

The laminar construct for tissue-engineered dermal equivalents is a sophisticated hydrogel matrix designed to facilitate the growth of both vascular and dermal tissues from a single source of mesenchymal stem cells (MSCs). This matrix is composed of at least two distinct hydrogel layers, each engineered to support the differentiation of MSCs into specific cell types.

One layer, made from materials such as fibrin, PEGylated fibrin, or hyaluronic acid, promotes the differentiation of MSCs into blood vessel cells. The other layer, incorporating materials like collagen types I-V, fibronectin, tenascin, vitronectin, or glycosaminoglycans, encourages MSCs to become dermal fibroblasts. MSCs can be introduced into the hydrogel matrix either by being sandwiched between the layers or seeded within them, potentially using microcarriers. This construct aims to reduce culture time and enhance the viability of the tissue-engineered skin by supporting the formation of both vascular and dermal tissues simultaneously.

What differentiates this technology is its ability to create a multi-layered tissue culture from a single source of stem cells, thereby simplifying the production process and reducing the time required for tissue culture. Traditional methods often require sequential culture of different cell types, which is time-consuming and complex. This technology leverages the unique properties of MSCs, which can differentiate into multiple cell types depending on their microenvironment.

By engineering the hydrogel matrix to control cell differentiation through its material properties, the need for external growth factors is minimized. Additionally, the inclusion of a blood vessel-promoting layer within the construct enhances the viability of the engineered tissue by ensuring adequate vascularization, which is crucial for nutrient delivery and waste removal. This innovation holds promise for more effective and efficient skin grafts, particularly for treating severe burns and non-healing ulcers.

Benefits

Reduces culture time for tissue-engineered skin
Enhances viability of tissue-engineered skin
Supports differentiation of stem cells into multiple cell types
Facilitates formation of both vascular and dermal tissue from a single stem cell source
Potentially fewer immune complications with autografts
Simultaneous formation of blood vessels and dermal connective tissue
Utilizes materials like fibrin, PEGylated fibrin, hyaluronic acid, and various collagens
Allows for stem cells to be introduced in multiple ways (sandwiched or seeded)