# Decellularized Extracellular Matrix/Gellan Gum Hydrogels Enriched with Spermine for Cardiac Models

**Authors:** Luca Di Nunno, Marcin Wekwejt, Francesco Copes, Francesca Boccafoschi, Diego Mantovani

PMC · DOI: 10.3390/gels12020118 · 2026-01-28

## TL;DR

Researchers created a new hydrogel material that mimics the structure and function of heart tissue for better in vitro cardiac models.

## Contribution

A novel hybrid hydrogel combining decellularized bovine pericardium ECM, gellan gum, and spermine is developed for cardiac tissue engineering.

## Key findings

- The hydrogels exhibit mechanical properties similar to native myocardium and long-term stability under physiological conditions.
- Hydrogel formulations showed an ECM-like porous structure and preserved cell viability and morphology in H9C2 cardiomyoblasts.
- SPM content concentration influenced the storage modulus, indicating tunable mechanical properties.

## Abstract

The physiological relevance of in vitro models is limited because conventional two-dimensional cell culture systems are unable to replicate the structural and functional complexity of native tissues. Extracellular matrix (ECM)-mimetic hydrogels have become important platforms for tissue engineering applications. This work developed hybrid hydrogels that mimic important biochemical and mechanical characteristics of cardiac tissue by combining decellularized bovine pericardium-derived (dBP) ECM, gellan gum (GG), and spermine (SPM). Although dBP offers tissue-specific biological cues, processing compromises its mechanical integrity. This limitation was overcome by adding GG, whose ionic gelation properties were optimized using DMEM and SPM. The hydrogels’ mechanical, biological, physicochemical, and structural characteristics were all evaluated. Under physiologically simulated conditions, the formulations showed quick gelation and long-term stability; scanning electron microscopy revealed an interconnected, ECM-like porous microarchitecture. While uniaxial compression testing provided Young’s modulus values comparable to native myocardium, rheological analysis revealed a concentration-dependent increase in storage modulus with increasing SPM content. H9C2 cardiomyoblasts were used in cytocompatibility studies to confirm that cell viability, morphology, and cytoskeletal organization were all preserved. All of these findings support the potential application of dBP−GG−SPM hydrogels in advanced in vitro cardiac models by showing that they successfully replicate important characteristics of cardiac ECM.

## Full-text entities

- **Genes:** MYOG (myogenin) [NCBI Gene 281343], DBP (D-box binding PAR bZIP transcription factor) [NCBI Gene 503577], ACTE1 (actin epsilon 1) [NCBI Gene 528168], Gja1 (gap junction protein, alpha 1) [NCBI Gene 24392] {aka Cx43, Cxnk1}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 100139219], LOC781146 (lysozyme) [NCBI Gene 781146]
- **Diseases:** injury to (MESH:D014947), disturbances (MESH:D014832), burn (MESH:D002056), Cardiovascular diseases (MESH:D002318), cytotoxic (MESH:D064420), death (MESH:D003643), type 2 diabetes (MESH:D003924), cardiac cytotoxicity (MESH:D006331)
- **Chemicals:** polysaccharide (MESH:D011134), nitrogen (MESH:D009584), streptomycin (MESH:D013307), polymer (MESH:D011108), chondroitin sulphate (MESH:D002809), COO (MESH:C041069), gold (MESH:D006046), 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (MESH:C410687), carrageenan (MESH:D002351), alginate (MESH:D000464), NH3+ (MESH:D000641), phalloidin (MESH:D010590), acetic acid (MESH:D019342), Ge (MESH:D005857), hyaluronic acid (MESH:D006820), phenol (MESH:D019800), water (MESH:D014867), SPM (MESH:D013096), amphotericin (MESH:D000666), amine (MESH:D000588), carbohydrate (MESH:D002241), DLa (-), aluminum (MESH:D000535), karaya gum (MESH:D007618), humic acid (MESH:D006812), glycosaminoglycans (MESH:D006025), glycerol (MESH:D005990), penicillin (MESH:D010406), glutaraldehyde (MESH:D005976), GG (MESH:C048288), PBS (MESH:D007854), spermidine (MESH:D013095), hydrogen (MESH:D006859), glucose (MESH:D005947), DAPI (MESH:C007293), calcium (MESH:D002118), polyamine (MESH:D011073), CO2 (MESH:D002245), L-glutamine (MESH:D005973), sucrose (MESH:D013395)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Bos taurus (bovine, species) [taxon 9913]
- **Cell lines:** H9C2 — Rattus norvegicus (Rat), Spontaneously immortalized cell line (CVCL_0286)

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12939898/full.md

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Source: https://tomesphere.com/paper/PMC12939898