Application Note | ElastoSens™ Bio
Extracellular Matrix (ECM) Hydrogels: Properties, Applications & Mechanical Behavior
by Maya Salame and Dimitria Camasao
Application Scientists
What Is an Extracellular Matrix (ECM) Hydrogel?
Extracellular matrix (ECM) hydrogels are biomaterials derived from native tissues after removal of cellular components through decellularization. The remaining matrix preserves key structural proteins (such as collagens, elastin, fibronectin, and laminin), proteoglycans, and glycosaminoglycans that define the biochemical and architectural identity of the source tissue. ECM is naturally produced by cells in all tissues and provides both mechanical support and biochemical signaling cues. ECM hydrogels are typically obtained from animal or human tissues—including cardiac, dermal, adipose, skeletal muscle, liver, lung, and others—by decellularization followed by enzymatic solubilization. Upon neutralization and warming to physiological temperature, the solubilized ECM self-assembles into a hydrated, three-dimensional hydrogel that partially recapitulates the native tissue microenvironment.
Key Properties of ECM Hydrogels
Physicochemical Characteristics
ECM hydrogel formation relies on the intrinsic self-assembly of matrix proteins rather than synthetic polymerization. After enzymatic digestion, ECM solutions undergo temperature- and pH-dependent gelation driven by collagen fibrillogenesis and protein–protein interactions.
Key physicochemical features include:
- Gelation mechanism: Thermally induced self-assembly at physiological temperature.
- Composition: Tissue-specific mixtures of collagens, proteoglycans, and adhesive proteins.
- Crosslinking strategies:
- Physical self-assembly without added crosslinkers.
- Optional secondary crosslinking using photo-oxidation, chemical agents, or natural crosslinkers to enhance stability.
- Environmental sensitivity: Gelation and final structure depend on temperature, ionic strength, pH, and ECM concentration.
These characteristics enable injectability at low temperature and in situ gel formation under physiological conditions.
Mechanical Properties
ECM hydrogels are typically soft and viscoelastic, with stiffness values well below those of native bulk tissues. Their mechanical behavior reflects both the tissue of origin and the extent of processing.
Mechanical features include:
- Low elastic modulus: Suitable for mimicking soft tissues.
- Tissue-specific mechanics: Cardiac, skeletal muscle, dermal, or brain-derived ECM hydrogels exhibit distinct stiffness profiles.
- Concentration dependence: Increasing ECM content raises gel stiffness and network density.
- Crosslinking effects: Secondary crosslinking enhances stiffness, resistance to deformation, and durability.
- Time-dependent evolution: Enzymatic degradation and remodeling lead to gradual mechanical changes over time.
Biological Interactions
ECM hydrogels retain bioactive motifs that regulate cell behavior through direct and indirect interactions.
Biological characteristics include:
- Cell adhesion: Presence of integrin-binding domains supports attachment and spreading.
- Biocompatibility: Decellularization reduces immunogenicity while preserving biological signals.
- Tissue-specific signaling: ECM composition influences cell phenotype, differentiation, and function.
- Enzymatic degradation: Cells remodel ECM hydrogels via protease-mediated pathways, enabling dynamic reciprocity between cells and matrix.
Applications of ECM Hydrogels
Tissue Engineering
ECM hydrogels are widely used as scaffolds for tissue repair and regeneration. Their tissue-specific composition supports constructive remodeling, cell infiltration, and vascularization. Applications span musculoskeletal repair, cardiac regeneration, dermal reconstruction, and neural tissue engineering, where ECM hydrogels provide both structural support and biological cues that guide tissue-specific regeneration.
3D Cell Culture & Disease Models
ECM hydrogels are increasingly employed as three-dimensional culture platforms that better replicate native tissue environments than synthetic matrices. They support organoid formation, tumor modeling, and studies of cell–matrix interactions. By preserving tissue-specific biochemical complexity, ECM hydrogels enable more physiologically relevant in vitro models for studying development, disease progression, and drug response.
Drug, Gene & Cell Delivery
Injectable ECM hydrogels function as localized delivery systems for therapeutic agents. Their porous structure allows incorporation and sustained release of drugs, growth factors, genes, or cells. ECM-based delivery systems improve retention at the target site, protect sensitive cargos, and leverage native matrix interactions to enhance therapeutic efficacy.
Why the Viscoelasticity of ECM Hydrogels Matters
The viscoelastic behavior of ECM hydrogels is central to their biological performance. Time-dependent stress relaxation and energy dissipation influence how cells sense mechanical cues, reorganize their cytoskeleton, and regulate gene expression. Viscoelasticity also governs load sharing, structural stability, and matrix remodeling during tissue regeneration. Because ECM hydrogels evolve mechanically as they degrade or are remodeled by cells, understanding their viscoelastic properties is essential for predicting long-term function in both in vitro and in vivo applications.
Methods to Characterize the Viscoelasticity of ECM Hydrogels
ECM hydrogel mechanics are commonly assessed using bulk rheometry, compression testing, and tensile measurements. These techniques provide information on storage and loss moduli, stiffness, and failure behavior. However, traditional methods often require direct contact, large deformations, or destructive testing, limiting their suitability for fragile, cell-laden, or dynamically evolving ECM hydrogels. They are also poorly adapted to monitoring early gelation, real-time mechanical changes, or long-term behavior under sterile conditions.
Case study: Mechanical Characterization of ECM Hydrogel Using ElastoSens™ Bio
ElastoSens™ Bio: A Non-Destructive Tool to Measure Soft ECM Hydrogels
The ElastoSens™ Bio is a non-destructive, contact-free instrument designed specifically for soft and highly hydrated materials such as ECM hydrogels. It operates by inducing low-amplitude vibrations and measuring the resulting mechanical response to extract viscoelastic properties in real time. Its high sensitivity and repeatability make it particularly suitable for weak, evolving matrices.
Key advantages include:
- Real-time monitoring of gelation kinetics and identification of the liquid–gel transition.
- Measurement of final stiffness and time-dependent mechanical evolution.
- Non-destructive testing of the same sample over extended periods.
- Compatibility with sterile and cell-laden workflows.
- Optional photostimulation module for real-time monitoring of photocrosslinking when applicable.
To demonstrate the capabilities of the ElastoSens™ Bio, ECM-based hydrogels were tested. The following section outlines the materials and methods employed, followed by the results, providing a practical example of the instrument’s ability to non-destructively monitor viscoelastic properties.
Material and methods
MatriXpec™ hydrogels are derived from the decellularization of porcine tissues and are designed to reproduce tissue-specific extracellular matrix (ECM) microenvironments for 3D cell culture, containing hundreds of native ECM proteins. MatriXpec™ products from porcine bone, skin, myocardium, kidney, vascular, lung, adipose, liver, spleen and muscle were prepared separately in 50 mL tubes. 18 mL of the liquid matrices were gently mixed with 2 mL of buffer and 6 mL of the solution were poured in each sample holder of the ElastoSens™ Bio. The measurements were taken at a temporal step of 20 s and at a temperature of 37 °C. The test duration ranged from 35 minutes to 5 hours depending on the product. Average results are expressed as mean ± standard deviation. The number of samples was equal to 3 (n = 3). MatriXpec™ products started to gel as soon as they were neutralized and placed at 37 °C (example shown in Figure 1).
Figure 1. Representative MatriXpec™ Lung hydrogel inside macro sample holder for testing.
Results and discussion
Using the ElastoSens™ Bio, the final viscoelastic properties of MatriXpec™ hydrogels prepared from adipose, bone, kidney, liver, lung, muscle, myocardial, skin, spleen, and vascular tissues were characterized (Figure 2). Final shear storage modulus (G′) values varied across tissues, ranging from ~600 Pa for bone- and skin-derived ECMs to ~870 Pa for spleen-derived ECM, with intermediate stiffness observed for myocardial, vascular, lung, adipose, and liver. The damping factor (tan δ) spanned approximately 0.1–0.4 across all formulations, indicating distinct balances between elastic and viscous contributions depending on tissue origin. In all cases, tan δ < 0.5, confirming a predominantly elastic mechanical response. These results demonstrate that ElastoSens™ Bio can resolve tissue-specific mechanical differences in ECM hydrogels, supporting their use in selecting and tuning biologically relevant microenvironments for 3D cell culture.
Figure 2. Final average shear storage modulus (G’, blue) and damping factor (tanδ, orange) of MatriXpec™ products.
Conclusions and perspectives
The mechanical behavior of ECM hydrogels—governed by their tissue-specific composition, viscoelasticity, and dynamic remodeling—is central to their biological performance and translational potential. As ECM hydrogels are soft, highly hydrated, and time-evolving, their mechanics must be characterized without disrupting structure or sterility.
- Non-destructive viscoelastic measurements tailored to soft ECM materials.
- High sensitivity and repeatability to capture weak, tissue-specific stiffness.
- Real-time monitoring of gelation kinetics, liquid–gel transition, and end stiffness.
- Longitudinal testing of the same sample to follow mechanical evolution under sterile conditions.
- Integrated photostimulation module enabling real-time monitoring of photocrosslinking when applicable.
Together, this approach supports deeper insight into ECM structure–property relationships and improves reproducibility across research and biomedical applications.
References
Heath, D. E. (2019). A review of decellularized extracellular matrix biomaterials for regenerative engineering applications. Regenerative Engineering and Translational Medicine, 5(2), 155-166.
Hinderer, S., Layland, S. L., & Schenke-Layland, K. (2016). ECM and ECM-like materials—Biomaterials for applications in regenerative medicine and cancer therapy. Advanced drug delivery reviews, 97, 260-269.
Yao, Q., Zheng, Y. W., Lan, Q. H., Kou, L., Xu, H. L., & Zhao, Y. Z. (2019). Recent development and biomedical applications of decellularized extracellular matrix biomaterials. Materials Science and Engineering: C, 104, 109942.
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