A method for fabricating biocompatible fiber-based hydrogels for safe and injectable biomedical applications

Background

Hydrogels are a class of water-swollen polymer networks that have found widespread use in biomedical fields such as tissue engineering, drug delivery, and wound healing due to their high water content, tunable mechanical properties, and biocompatibility. Among the various types of hydrogels, fiber-based hydrogels—composed of entangled microfibers—offer unique advantages, including enhanced mechanical strength, high porosity, and the ability to mimic the fibrous architecture of natural extracellular matrices. These features make them especially attractive for applications where cell infiltration, nutrient transport, and integration with biological tissues are critical. As the demand for advanced biomaterials grows, there is a pressing need for hydrogel systems that are not only structurally and functionally sophisticated but also safe and practical for clinical use.

Despite their promise, current fabrication methods for fiber-based hydrogels often rely on oil/aqueous emulsions, organic solvents, or surfactants to generate and process the microfibers. These approaches introduce significant challenges: residual oils or solvents can be cytotoxic, denature proteins, and reduce cell viability, necessitating extensive and costly post-processing to remove contaminants. Additionally, the presence of surfactants or organic phases can complicate regulatory approval and limit the use of such hydrogels in sensitive biomedical applications. Furthermore, chemical crosslinking between fibers, often used to stabilize the network, can introduce additional toxicity and reduce the hydrogel’s ability to support living cells. These limitations underscore the need for new fabrication strategies that eliminate toxic components, simplify processing, and yield hydrogels with high biocompatibility and structural integrity.

Technology

This technology is an innovative method for fabricating fiber-based hydrogels using an all-aqueous, oil- and surfactant-free process, resulting in highly biocompatible and injectable materials. The process employs an aqueous two-phase system (ATPS) within a flow-focusing microfluidic device, where an aqueous polymer solution containing a photoinitiator is contacted with another aqueous phase. Under UV light and controlled shear, this setup produces high aspect ratio microfibers (length-to-diameter ratio ≥100, often much higher), which are suspended in water. When extruded, these microfibers mechanically interlock, forming a porous hydrogel network without the need for chemical crosslinking between fibers. The resulting hydrogels typically comprise 1–7% microfibers by dry weight and 93–99% water, with porosity levels that support the incorporation of therapeutic agents or cells, making them suitable for diverse biomedical applications such as tissue engineering, drug delivery, wound healing, and regenerative medicine.

What differentiates this technology is its elimination of toxic organic solvents, surfactants, and oil phases that are commonly used in traditional microfiber hydrogel fabrication. By relying solely on aqueous phases and mechanical interlocking, the process significantly reduces the risk of cytotoxicity, protein denaturation, and cell viability loss, while also simplifying post-processing and lowering production costs. The method’s versatility allows for the use of a wide range of hydrophilic, biocompatible polymers, enabling customization for specific medical needs. Experimental data confirm high cell viability and compatibility, supporting its use in sensitive biomedical contexts. The injectable, in situ-forming nature of the hydrogel further enhances its practicality for minimally invasive therapies, setting it apart from conventional hydrogels that often require more complex handling or pose greater safety concerns.

Benefits

• Eliminates use of toxic organic solvents and surfactants, enhancing biocompatibility and safety for biomedical applications.
• Produces high aspect ratio microfibers (≥100) that mechanically interlock to form a stable, porous hydrogel network.
• Utilizes an all-aqueous two-phase system (ATPS) enabling gentle fabrication with ultralow interfacial tension, preserving cell viability and protein integrity.
• Injectable hydrogel forms in situ upon extrusion, facilitating minimally invasive delivery for tissue engineering, drug delivery, and wound healing.
• Wide range of biocompatible polymers can be used, allowing customization for diverse medical uses.
• Porous structure (5–30% porosity) supports incorporation of therapeutic agents and promotes cell growth.
• Reduces post-processing costs and complexity by avoiding chemical crosslinking and toxic residual removal.
• Demonstrated high cell viability and compatibility through MTT assays and cell growth studies.

Applications

• Injectable tissue engineering scaffolds
• Drug delivery hydrogel systems
• Wound dressing and healing
• Surgical sealants and adhesives
• Nerve regeneration scaffolds

Additional info

This process utilizes an aqueous two-phase system to fabricate hydrogels composed of 1-7% high aspect ratio microfibers. UV-crosslinked in microfluidic channels, these biocompatible fibers achieve mechanical interlocking through shear-induced topological entanglement during extrusion. The resulting network lacks chemical crosslinks between fibers, surfactants, or organic solvents. Containing 93-99% water, this porous, injectable material is optimized for biomedical applications, including tissue engineering and drug delivery.