# Biomimetic electrospun scaffolds for engineered heart tissue: from design parameters to drug testing platforms

**Authors:** Raminta Vaiciuleviciute, Aidas Alaburda, Ilona Uzieliene, Kornél Kistamás, Máté Lengyel, András Dinnyés, Christian Bergaud, Eiva Bernotiene

PMC · DOI: 10.3389/fbioe.2026.1711698 · Frontiers in Bioengineering and Biotechnology · 2026-02-10

## TL;DR

This paper reviews how electrospun nanofibers can mimic heart tissue and improve drug testing, focusing on design factors that influence cell function.

## Contribution

The paper provides a comprehensive synthesis of design parameters for electrospun scaffolds to enhance cardiomyocyte maturation.

## Key findings

- Electrospun scaffolds with specific fiber diameters and alignment improve cardiomyocyte function.
- Conductive polymers enhance electrical coupling in stem cell-derived cardiomyocytes.
- Challenges remain in achieving full maturation of cardiomyocytes on these scaffolds.

## Abstract

Electrospun nanofibers have emerged as a promising platform for cardiac tissue engineering, offering unique opportunities to recapitulate the native myocardial extracellular matrix (ECM) architecture. This comprehensive review examines the critical design parameters affecting cardiomyocyte function and maturation on electrospun scaffolds, including fiber diameter, material composition, alignment, and pore architecture. Recent advances in conductive polymers and hybrid material systems have shown particular promise for enhancing electrical coupling and functional maturation of stem cell-derived cardiomyocytes. However, significant challenges remain in achieving complete cardiomyocyte maturation, particularly regarding calcium handling properties and metabolic characteristics. This review synthesizes current knowledge on technical characteristics of biomimetic nanofibrous scaffolds, identifying future directions for translating these approaches toward realistic cardiac models and potential clinical cardiac regenerative applications.

## Full-text entities

- **Genes:** NKX2-5 (NK2 homeobox 5) [NCBI Gene 1482] {aka CHNG5, CSX, CSX1, HLHS2, NKX2.5, NKX2E}, TTN (titin) [NCBI Gene 7273] {aka CMD1G, CMH9, CMPD4, CMYO5, CMYP5, EOMFC}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, KCNA4 (potassium voltage-gated channel subfamily A member 4) [NCBI Gene 3739] {aka HBK4, HK1, HPCN2, HUKII, KCNA4L, KCNA8}, PTK2 (protein tyrosine kinase 2) [NCBI Gene 5747] {aka FADK, FADK 1, FAK, FAK1, FRNK, PPP1R71}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, TIMP1 (TIMP metallopeptidase inhibitor 1) [NCBI Gene 7076] {aka CLGI, EPA, EPO, HCI, TIMP, TIMP-1}, KCNJ2 (potassium inwardly rectifying channel subfamily J member 2) [NCBI Gene 3759] {aka ATFB9, HHBIRK1, HHIRK1, IRK1, KIR2.1, LQT7}, FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, TNNI1 (troponin I1, slow skeletal type) [NCBI Gene 7135] {aka SSTNI, TNN1}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, PDGFRB (platelet derived growth factor receptor beta) [NCBI Gene 5159] {aka CD140B, IBGC4, IMF1, JTK12, KOGS, OPDKD}, AGT (angiotensinogen) [NCBI Gene 183] {aka ANHU, SERPINA8, hFLT1}, MLC1 (modulator of VRAC current 1) [NCBI Gene 23209] {aka LVM, MLC, VL}, CCND2 (cyclin D2) [NCBI Gene 894] {aka KIAK0002, MPPH3}, PLCL1 (phospholipase C like 1 (inactive)) [NCBI Gene 5334] {aka PLCE, PLCL, PLDL1, PPP1R127, PRIP}, ELN (elastin) [NCBI Gene 2006] {aka ADCL1, SVAS, WBS, WS}, MYH7 (myosin heavy chain 7) [NCBI Gene 4625] {aka CMD1S, CMH1, CMYO7A, CMYO7B, CMYP7A, CMYP7B}, NPPA (natriuretic peptide A) [NCBI Gene 4878] {aka ANF, ANP, ATFB6, ATRST2, CDD, CDD-ANF}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, CASQ2 (calsequestrin 2) [NCBI Gene 845] {aka PDIB2}, MMRN1 (multimerin 1) [NCBI Gene 22915] {aka ECM, EMILIN4, GPIa*, MMRN}, GJA5 (gap junction protein alpha 5) [NCBI Gene 2702] {aka ATFB11, CX40}, BMP1 (bone morphogenetic protein 1) [NCBI Gene 649] {aka OI13, PCOLC, PCP, TLD}, NPNT (nephronectin) [NCBI Gene 255743] {aka EGFL6L, POEM}, SIRPA (signal regulatory protein alpha) [NCBI Gene 140885] {aka BIT, CD172A, MFR, MYD-1, MYD1, P84}, TNNT1 (troponin T1, slow skeletal type) [NCBI Gene 7138] {aka ANM, NEM5, STNT, TNT, TNTS}, GJA1 (gap junction protein alpha 1) [NCBI Gene 2697] {aka AVSD3, CMDR, CX43, EKVP, EKVP3, GJAL}, MYL2 (myosin light chain 2) [NCBI Gene 4633] {aka CMH10, MFM12, MLC-2, MLC-2s/v, MLC-2v, MLC2}, SCN5A (sodium voltage-gated channel alpha subunit 5) [NCBI Gene 6331] {aka CDCD2, CMD1E, CMPD2, HB1, HB2, HBBD}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, FGB (fibrinogen beta chain) [NCBI Gene 2244] {aka HEL-S-78p}, KDR (kinase insert domain receptor) [NCBI Gene 3791] {aka CD309, FLK1, VEGFR, VEGFR2}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, ATP2A2 (ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2) [NCBI Gene 488] {aka ATP2B, DAR, DD, RHABDO2, SERCA2}, TNNT2 (troponin T2, cardiac type) [NCBI Gene 7139] {aka CMD1D, CMH2, CMPD2, LVNC6, RCM3, TnTC}, TAFAZZIN (tafazzin, phospholipid-lysophospholipid transacylase) [NCBI Gene 6901] {aka BTHS, CMD3A, EFE, EFE2, G4.5, LVNCX}, HLA-C (major histocompatibility complex, class I, C) [NCBI Gene 3107] {aka D6S204, HLA-JY3, HLAC, HLC-C, MHC, PSORS1}, PECAM1 (platelet and endothelial cell adhesion molecule 1) [NCBI Gene 5175] {aka CD31, CD31/EndoCAM, GPIIA', PECA1, PECAM-1, endoCAM}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, MYH6 (myosin heavy chain 6) [NCBI Gene 4624] {aka ASD3, CMD1EE, CMH14, MYHC, MYHCA, SSS3}, TIMP2 (TIMP metallopeptidase inhibitor 2) [NCBI Gene 7077] {aka CSC-21K, DDC8}, CXXC1 (CXXC finger protein 1) [NCBI Gene 30827] {aka 2410002I16Rik, 5830420C16Rik, CFP1, CGBP, HsT2645, PCCX1}, MYL7 (myosin light chain 7) [NCBI Gene 58498] {aka MYL2A, MYLC2A}, EDN1 (endothelin 1) [NCBI Gene 1906] {aka ARCND3, ET1, HDLCQ7, PPET1, QME}, EFNB1 (ephrin B1) [NCBI Gene 1947] {aka CFND, CFNS, EFB1, EFL3, EPLG2, Elk-L}, ISL1 (ISL LIM homeobox 1) [NCBI Gene 3670] {aka ISLET1, Isl-1}, YAP1 (Yes1 associated transcriptional regulator) [NCBI Gene 10413] {aka COB1, YAP, YAP-1, YAP2, YAP65, YKI}, HCN1 (hyperpolarization activated cyclic nucleotide gated potassium channel 1) [NCBI Gene 348980] {aka BCNG-1, BCNG1, DEE24, EIEE24, GEFSP10, HAC-2}, TNNI3 (troponin I3, cardiac type) [NCBI Gene 7137] {aka CMD1FF, CMD2A, CMH7, RCM1, TNNC1, cTnI}, EGF (epidermal growth factor) [NCBI Gene 1950] {aka HOMG4, URG}, RHOA (ras homolog family member A) [NCBI Gene 387] {aka ARH12, ARHA, EDFAOB, RHO12, RHOH12}, IL33 (interleukin 33) [NCBI Gene 90865] {aka C9orf26, DVS27, IL1F11, NF-HEV, NFEHEV}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}
- **Diseases:** hypertension (MESH:D006973), deaths (MESH:D003643), atrial fibrillation (MESH:D001281), hypertrophy (MESH:D006984), CVDs (MESH:D002318), developmental toxicity (MESH:D064420), heart failure (MESH:D006333), infarct (MESH:D007238), EHT (MESH:D006331), QT prolongation (MESH:D008133), necrotic (MESH:D009336), fibrosis (MESH:D005355), inflammatory (MESH:D007249), AD (MESH:D000544), preserved (MESH:C537758), CF (MESH:D003550), arrhythmia (MESH:D001145), hypoxic (MESH:D002534), D-PHI (MESH:D014808), arrhythmic (OMIM:212500), cardiotoxic (MESH:D066126), hypoxia (MESH:D000860)
- **Chemicals:** graphene (MESH:D006108), 3i-1262 (-), glycosaminoglycans (MESH:D006025), Carbon nanotube (MESH:D037742), Polyvinyl Alcohol (MESH:D011142), fatty acid (MESH:D005227), PCL (MESH:C016240), PDMS (MESH:C013830), ISO (MESH:D007545), ATP (MESH:D000255), PLA (MESH:C033616), LPS (MESH:D008070), lipid (MESH:D008055), verapamil (MESH:D014700), PU (MESH:D011140), heparin (MESH:D006493), MXene (MESH:C000723374), PLGA (MESH:D000077182), Poly (lactide-co-glycolide) (MESH:D011098), calcium (MESH:D002118), poly (2-ethyl 2-oxazoline) (MESH:C511916), gold (MESH:D006046), Poly(lactide-co-epsilon-caprolactone) (MESH:C062968), NH3 (MESH:D000641), alginate (MESH:D000464), oxygen (MESH:D010100), PSS (MESH:C003321), Chitosan (MESH:D048271), Graphene oxide (MESH:C000628730), PPy (MESH:C067635), ethylene oxide (MESH:D005027), Carbon (MESH:D002244), polymer (MESH:D011108), Polyacrylamide (MESH:C016679), PANi (MESH:C416807), poly (ester-urethane) urea (MESH:C497893), Silicone (MESH:D012828), Poly(3,4-ethylenedioxythiophene) (MESH:C121383), HA (MESH:D006820), NO (MESH:D009569)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090], Crohivirus B (no rank) [taxon 2169854]
- **Cell lines:** NIH/3T3 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0594), C2C12 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0188), HL-1 — Mus musculus (Mouse), Transformed cell line (CVCL_0303), H2C9 — Rattus norvegicus (Rat), Spontaneously immortalized cell line (CVCL_0286)

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12929422/full.md

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12929422/full.md

## References

238 references — full list in the complete paper: https://tomesphere.com/paper/PMC12929422/full.md

---
Source: https://tomesphere.com/paper/PMC12929422