Injectable Collagen-Alginate Hydrogel for Post-Injection Stability
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Solution Overview
Problem
Existing injectable collagen-based hydrogels face challenges such as instability, leakage, and dilution in the body, limiting their use in regenerative medicine and 3D bioprinting due to low viscosity and structural instability, as well as the need for additional crosslinking stimuli or special instrumentation.
Innovation Solution
Development of an in-situ stable injectable collagen-based hydrogel by incorporating alginate and calcium sulfate (CaSO4) into the matrix, creating a shear-thinning hydrogel that crosslinks at physiological conditions, maintaining stability and mechanical properties post-injection, allowing for effective delivery of cells and growth factors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If uncrosslinked collagen hydrogel precursor solution is used for delivery, then injectability is achieved, but stability and structural integrity are lost leading to leakage and dilution
Solution Approach 1:
The hydrogel is pre-crosslinked before injection to establish structural stability, yet maintains shear-thinning properties that allow it to flow through injection needles. The pre-formed hydrogel beads or microgels are suspended in an injectable vehicle, combining stability with deliverability.
Solution Approach 2:
The hydrogel exhibits shear-thinning behavior where viscosity decreases under shear stress (during injection) and increases at rest (after injection). This parameter change allows the same material to be both injectable and stable, resolving the contradiction between ease of operation and stability.
2Stability of the object's composition
If pre-crosslinked shear-thinning hydrogels are used, then stability and resistance to leakage are improved, but they get diluted or washed away after injection
Solution Approach 1:
The system combines pre-crosslinked hydrogel beads (提供结构稳定性和防泄漏性) with an injectable vehicle or carrier (提供流动性和抗稀释性). This composite structure allows the hydrogel to resist leakage while maintaining substance concentration after injection.
3Ease of operation
If in-situ crosslinkable injectable hydrogels are used, then injectability is maintained, but they are influenced by in-vivo microenvironment and require additional stimuli for crosslinking
Solution Approach 1:
Crosslinking is performed in advance before injection, eliminating the need for in-situ crosslinking stimuli. The pre-crosslinked hydrogel maintains its structural integrity while being delivered to the target site, simplifying the overall process.
4Stability of the object's composition
If collagen fibrils are mixed with injectable alginate hydrogel to increase stability, then post-injection stability is improved, but preprocessing steps and special instrumentation are required
Solution Approach 1:
The invention creates a composite system of pre-crosslinked collagen-based hydrogel beads suspended in an injectable vehicle. This approach achieves enhanced stability without requiring complex preprocessing of collagen fibrils or special coaxial nozzle instrumentation.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The Alg/Col hydrogel achieves high post-injection stability, prevents leakage, and supports cell viability and proliferation, making it suitable for regenerative medicine and bioprinting applications with tunable viscoelastic characteristics and improved structural integrity.
Implementation Method 1
shear-thinning injectable hydrogels, that are partially or fully crosslinked before injection, flow through syringe and needles under the applied shear stress and with that take the shape of the defect cavity
Implementation Method 2
Due to their large water content, porous microstructure and permeability to oxygen, nutrients, proteins and cell waste products, hydrogels provide a three-dimensional (3D) microenvironment for cell encapsulation
Implementation Method 3
crosslinks at 37 degrees Celsius and physiological pH and loses its injectability following crosslinking
Data Source
AI summary
A stable injectable collagen-based hydrogel delivery platform and method is provided to obtain the viscosity, post-injection stability and mechanical properties needed of an injectable collagen matrix via incorporating alginate and calcium sulfate (CaSO4) into the matrix. The hydrogel (Alg/Col hydrogel) is shear-thinning, injectable through commercially available needles and stable right after injection.