. 2020 Jun 17;2(2):101–119. doi: 10.1089/bioe.2020.0010

Table 1.

Summary of Polypyrrole-Containing Scaffolds Used in Tissue Engineering and Their Formats, Properties, and Performances

Main material	Scaffold format	PPy incorporation	Dopant/oxidant	Concentration	Electrical properties	Cell sources and usages	In vitro/vivo results	Ref.
ALG	Crosslinked hydrogel	Immerse coating	N.A./FeCl₃	[py]: 0–20 × 10⁻³ M	py[10]/ALG: 1.1 ± 0.3 × 10⁻⁴ S/cm	In vivo model/NTE	PPy/ALG hydrogels enhanced expression of Tuj1 and MAP2.	43
ALG	Crosslinked hydrogel	Immerse coating	N.A./FeCl₃	[py]: 0–20 × 10⁻³ M	py[10]/ALG: 1.1 ± 0.3 × 10⁻⁴ S/cm	In vivo model/NTE	Mild inflammatory reactions after 8 weeks of implantation.	43
ALG/COL	Crosslinked hydrogel	Mix ALG/COL with doped PPy	HCl/FeCl₃	ALG-graft-PPy: ALG (wt%): 20:80, 30:70	20%: 220 mS/cm	hMSCs/biocompatibility	No cytotoxicity effects.	9
ALG/COL	Crosslinked hydrogel	Mix ALG/COL with doped PPy	HCl/FeCl₃	ALG-graft-PPy: ALG (wt%): 20:80, 30:70	30%: 229 mS/cm	hMSCs/biocompatibility	No cytotoxicity effects.	9
ALG/CHI	Crosslinked hydrogel	Mix ALG/CHI with doped PPy	HCl/APS	PPy: 0.02–0.4 g	7.35 × 10⁻⁶–8.03 × 10⁻³ S/cm	PC12, RSC96, BMMSC/NTE	SA/CMCS/PPy hydrogels supported cell growth and proliferation.	39
							No severe inflammatory tissue responses when implanted in vivo.
							Better nerve fibers morphology in SA/CMCS/PPy hydrogels than the autologous nerve group.
ALG/CHI	Doubled lyophilized foam	Mix ALG/CHI with py, then polymerize	HCl/FeCl₃	[py]: 0.1 M	550–1000 nA	MG-63/BTE	CHI/PPy/ALG scaffold promoted the formation of apatite layer.	44
CHI	Crosslinked hydrogel	Mix CHI with py, then polymerize	N.A./FeCl₃	[PPy]: 0.04%	N.A.	NRCM/CTE	Synchronous contraction of two distinct clusters of CMs connected by PPy/CHI composite.	37
CHI	Crosslinked hydrogel	Mix CHI with py, then polymerize	N.A./FeCl₃	[PPy]: 0.04%	N.A.	NRCM/CTE	Higher EMG signal amplitude in scar tissue from PPy/CHI-treated animals.	37
CHI	Crosslinked gelfoam	Mix CHI with py, then polymerize	N.A./FeCl₃	N.A.	12.5 × 10⁻⁵ S/cm	NRCM/CTE	Higher calcium transient velocity of CMs on PPy composite.	38
CHI	Crosslinked gelfoam	Mix CHI with py, then polymerize	N.A./FeCl₃	N.A.	12.5 × 10⁻⁵ S/cm	NRCM/CTE	Faster conduction velocity on the epicardial surface of PPy composite-implanted hearts.	38
COL	IPC-mesh	Immerse coating	Cl⁻/FeCl₃	N.A.	N.A.	hMSC/NTE	Upregulated expression of noggin, MAP2, neurofilament, β tubulin III, and nestin from hMSCs on PPy/COL scaffolds.	62
COL	Hybrid microfibers hydrogel	Mix synthesized PPy with COL	N.A./FeCl₃	[PPy]: 0–1 mg/mL	Col 0.5: 0.22 S/m	PC12/NTE	Enhanced electroconductivity in PPy/COL hydrogel microfibers.	63
				[COL]: 6 mg/mL
				[COL]: 6 mg/mL			Improved PC12 cells neurogenesis.
COL/PAR	Inkjet-printed scaffold	Print on top of PPy lines	PVA/FeCl₃, FepTS	py: 136 mg	1.1 S/cm	PC12/NTE	Promoted neurite outgrowth and orientation on PPy/COL scaffold with electrical stimulation.	70
GX	Hydrogel	Electrochemically polymerization	GX/N.A.	[Py]: 0.4 M	Voltammetric peak: 0.2 (ox), −0.3 V (red)	Human fibroblast	Better cell adhesion on PPy/GX scaffold.	61
GX	Hydrogel	Electrochemically polymerization	GX/N.A.	[Py]: 0.4 M	Voltammetric peak: 0.2 (ox), −0.3 V (red)	Human fibroblast	External magnetic field helped cell adhesion and proliferation.	61
SF	Lyophilized foam	Immerse coating	HCl/APS	[py]: 14.28 mM	N.A.	hMSC/BTE	Increased collagen production of the hMSCs on PPy/SF scaffolds.	49
SF	Acid modified film	Immerse coating	p-TSA/FeCl₃	[py]: 50 mM	200–500 Ω/sq	hESC-derived CMs/CTE	Anisotropic topographical cues led to increased cellular organization and sarcomere development.	52
SF	Acid modified film	Immerse coating	p-TSA/FeCl₃	[py]: 50 mM	200–500 Ω/sq	hESC-derived CMs/CTE	Electroconductive cues promoted CX43 expression and polarization.	52
SF	3D print and electrospinning composite	Immerse coating	HCl/FeCl₃	[py]: 14 mM	1 × 10⁻⁵–1 × 10⁻³ S/cm	Mouse fibroblasts, SCs/NTE	No cytotoxicity and did not affect SC proliferation.	1
SF	Electrospun mat	Immerse coating	NaCl/FeCl₃	[py]: 0.3 M	Similar voltammograms to free-standing PPy	hMSC, hfibroblasts/Biocompatibility	No cytotoxicity and supported cell proliferation in vitro.	50
HA	Hydrogel	Immerse coating	N.A./APS	[py]: 0–100 Mm	10⁻³–10⁻² S/cm	3T3/Biocompatibility	PPy/HA composites supported cell attachment and proliferation.	59
HA/GEL	Self-adhesive hydrogel	Paint dopa-PPy on dopa-Gel/HA	N.A./FeCl₃	[dopa-PPy]: 0–0.6%	1.09 ± 0.06 × 10⁻⁶–2.85 ± 0.18 × 10⁻⁴ S/cm	In vivo model/CTE	Dopa-Gel/PPy hydrogel could tightly adhere to the porcine myocardium.	60
				[dopa-Gel]: 25%
				[dopa-Gel]: 25%			Smaller infarct sizes and thicker left ventricle walls.
HAp	Lyophilized foam	Mix HAp with doped PPy	N.A./N.A.	ppy: 0.26% w/v	N.A.	Osteoblast/BTR	Higher protein adsorption and drug release rate over a long period in PPy contained composites.	69
PCL	Film	Immerse coating	p-TSA/FeCl₃	[py]: 0.084 M	1.0 ± 0.4 kΩ cm	HL1/CTE	Higher calcium wave propagation and shorter transient duration on PPy/PCL composites.	10
PCL	Electrospunelectrospray mat	py vapor	p-TSA/FeCl₃	Oxidant electrospraying time: 1–4 h	1.3–1.9 S/cm	L929/Biocompatibility	PPy/PCL scaffold promoted PC12 attachment or proliferation.	65
PCL	Rolled 3D-printed scaffold	Mix PPy-block-PCL with PCL pellets	N.A./N.A.	[PPy-b-PCL]: 0.5–2%, PCL: 70%	0.28 ± 0.02–1.15 ± 0.03 mS/cm	hESC-derived NSCs/NTE	PCL/PPy scaffold enhanced cell maturation toward peripheral neuronal cells.	66
PCL/GEL	Electrospun mat	Disperse doped PPy in spinning solution	N.A./N.A.	PPy/PCL-GEL (PPG): 15:85, 30:70	PPG15: 0.013 mS/cm	Rabbit primary CM/CTE	Higher expression of CX43 in PPy/PCL scaffolds.	13
PCL/GEL	Electrospun mat	Disperse doped PPy in spinning solution	N.A./N.A.	PPy/PCL-GEL (PPG): 15:85, 30:70	PPG30: 0.37 mS/cm	Rabbit primary CM/CTE	Higher expression of CX43 in PPy/PCL scaffolds.	13
PLCL/SF	Electrospun mat	Immerse coating	p-TSA/FeCl₃	[py]: 2 M, volume: 0–50 μL	8.52 × 10⁻⁶–1.36 × 10⁻⁴	In vivo model/NTE	PPy/PLCL/SF mat promoted SCs proliferation in vivo.	6
PLCL/SF	Electrospun mat	Immerse coating	p-TSA/FeCl₃	[py]: 2 M, volume: 0–50 μL	8.52 × 10⁻⁶–1.36 × 10⁻⁴	In vivo model/NTE	Thicker myelin in regenerated nerve and better sciatic nerve function recovery.	6
PCL/PSS	Electrospun mat	Immerse coating	N.A./FeCl₃	[py]: 84 mM	52.8 ± 4.7 kΩ/sq	hMSCs/BTE	Increased ALP expression and calcium deposition on PPy/PCL/PSS scaffolds both with and without electrical stimulation.	64
PGA	Thermosetting injectable spring	Immerse coating after dopamine treatment	N.A./FeCl₃	[PY]: 0.2 M	80.84 S/m	HUVECs, RAECs, in vivo model/CTE	Highly oriented sarcomeres.	94
							Enhanced CM's maturation in synchronous contraction.
							Decreased ventricle infarct size.
PLA	Electrospun mat	Mix synthesized PPy in spinning solution	p123/FeCl₃	[PPy]: 1.8%	N.A.	In vivo model/NTE	PPy/PLA nanofibrous scaffold inhibited scar tissue formation.	79
				[PLA]: 12.5%
				[PLA]: 12.5%			Induced the axonal regeneration and myelination in the lesion area.
PLA	Electrospun mat	Mix synthesized PPy in spinning solution	p123/FeCl₃	[PPy]: 15%	1.10 × 10⁻⁴ S/cm	In vivo model/NTE	Six weeks after injury, the use of PLA/PPy scaffolds significantly reduced the activation of astrocytes and increased axonal regeneration.	80
PLA/PLO	Electrospun mat	Disperse doped PPy in spinning solution	N.A./N.A.	PPy:PLA (wt/wt): 1–10	N.A.	PC12/NTE	PPy-containing scaffolds supported PC12 cells differentiation without electrical stimulation, which could be further enhanced with electrical stimulation.	4
PLGA	Micro-grooved scaffold	Immerse coating	NaCl/FeCl₃	[py]: 2.875, 5.75, 11.5 mM	9.63–38.56 S/cm	mNSCs/NTE	Enhanced mNSCs neuronal differentiation on PPy-coated microgroove scaffolds even without electrical stimulation, which was further enhanced with electrical stimulation.	77
PLGA	Electrospun mat	py vapor, electrochemical polymerization	NaDBS/FeCl₃	[py]: 0.1 M	N.A.	iPSC/CTE	iPSCs on conductive scaffolds showed elevated expression of Actinin, NKX2.5, GATA4, and Myh6 both stimulated and unstimulated.	67
PLGA	Electrospun mat	Immerse coating	pTS/FeCl₃	[py]: 14 mM	7.4 ± 3.2 × 10³–9.0 ± 6.0 × 10⁴ Ω/sq	PC12/NTE	PPy/PLGA meshes supported differentiation of PC12.	68
PLGA	Electrospun mat	Immerse coating	pTS/FeCl₃	[py]: 14 mM	7.4 ± 3.2 × 10³–9.0 ± 6.0 × 10⁴ Ω/sq	PC12/NTE	Longer neurites on conductive scaffold with electrical stimulation than nonstimulated ones.	68
PGS/COL	Film	Mix PPy with PGS/Col solution	N.A./N.A.	[COL]: 0%, 0.5%	COL 0.5–PPy 5: 0.06 ± 0.14 S/cm	H9C2/CTE and drug release	PPy and collagen improved scaffolds' protein adsorption ability.	95
				[PPy]: 0–5%
							5% PPy did not change the degradation speed of the patch.
							Drug-loaded film promoted cell proliferation till 21 days.

ALG, alginate; ALP, alkaline phosphatase; APS, ammonium persulfate; BMMSC, bone marrow mesenchymal stem cell; BTE, bone tissue engineering; CHI, chitosan; CM, cardiomyocyte; CMCS, carboxymethyl chitosan; COL, collagen; CTE, cardiac tissue engineering; CX43, Connexin 43; dopa, dopamine; FeCl₃, ferric chloride; FepTS, ferric p-toluene sulfonate; GEL, gelatin; HA, hyaluronic acid; HAp, synthetic hydroxyapatite; HCl, hydrochloric acid; hESC, human embryonic stem cell; hMSCs, human mesenchymal stem cells; HUVECs, human umbilical vein endothelial cells; IPC, interfacial polyelectrolyte complexation; iPSCs, induced pluripotent stem cells; mNSCs, mouse neural stem cells; N.A., not applicable; NaDBS, sodium dodecylbenzenesulfonate; NRCM, neonatal rat cardiomyocytes; NTE, neural tissue engineering; p123, poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol); PAR, polyarylate; PCL, polycaprolactone; PGS, poly(glycerol sebacate); PLA, polylactic acid; PLCL, poly(l-lactic acid-co-ɛ-caprolactone); PLGA, poly(lactic-co-glycolic acid); PLO, poly-ornithine; py, pyrrole; PPy, polypyrrole; PSS, polystyrenesulfonate; PT, polythiophene; p-TSA, p-toluene sulfonic acid; PVA, polyvinyl alcohol; RAECs, rat aortic endothelial cells; SA, sodium alginate; SC, Schwann cell; SF, silk fibroin.