Biopolymeric 3D printed scaffolds as a versatile tissue engineering treatment for congenital diaphragmatic hernia

Abstract

Congenital diaphragmatic hernia (CDH) is a rare disease in which neonates are born with pulmonary hypoplasia and a diaphragmatic defect. Survival is improving due to advances in fetal intervention for pulmonary hypoplasia leading to increased use of scaffolds for repair. Scaffolds have a significant morbidity rate with recurrence, small bowel obstruction and infrequently postoperative infections. 3D printing (3DP) is a promising technology for the fabrication of personalized medical devices characterised by a more precise and targeted approach to tissue engineering and drug delivery.

Highlights

• 3D printing enables personalized fabrication of biocompatible scaffolds for CDH.
• HME and 3DP were optimized to produce homogenous filaments and precise printlets.
• All extruded scaffolds showed thermal stability and high elasticity.
• GNS-loaded scaffolds demonstrated sustained release and antibacterial efficacy.
• All 3D printed samples showed cytocompatibility.

In this study, blank thermoplastic polyurethane (TPU) and gentamicin sulfate (GNS)-loaded filaments (1 % and 1.5 %wt.) were fabricated with hot melt extrusion (HME) and subsequently processed through 3DP for scaffold manufacturing. Geometrical attributes of the scaffolds, including a specific % infill, were predefined through computer aided design (CAD) and printing parameters were optimised. Physicochemical analysis involving material compatibility and thermal properties of all formulations were examined, determining their thermal and chemical stability during 3DP.

Mechanical analysis showed that polymeric matrixes resemble to diaphragm tissue, exhibiting adequate and reproducible elastic performance, while cell studies confirmed TPU’s supportive capacity for cellular attachment. Additionally, in vitro dissolution and bacterial studies were carried out for up to a week, denoting GNS’s sustained release from the polymeric matrices and efficient bactericidal activity to Gram-positive and Gram-negative bacteria, respectively. Therefore, TPU is a potential biomaterial that can be efficiently used for developing diverse 3D printed diaphragm-like scaffolds possessing antimicrobial activity for CDH.

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Materials

TPU pellets (Ellastolan®; shore hardness of 85A) were provided by BASF (UK). The GNS powder (590 units/mg) was purchased by Tokyo Chemical Industries Ltd. (Oxford, UK). Castor oil, used as a binder of GNS on pellets surface, was obtained from Ransom (Hitchin, UK). Phosphate buffered saline (PBS) tablets, methanol, potassium dihydrogen orthophosphate, orthophosphoric acid, triethylamine, collagen (type 1 rat tail) were acquired by Sigma Aldrich© (Gillingham, UK). Moreover, Staphylococcus aureus (S. aureus ATCC 29213) and Escherichia Coli (E.coli ATCC 25922) were supplied from LGC Standards Ltd (Middlesex, UK). Mueller Hinton broth (MHB) and Mueller Hinton agar (MHA) were obtained from Oxoid Ltd. (UK). Endothelial Colony Forming Cells (ECFCs) were purchased by Lonza Ltd. (Slough, UK), and 10 % fetal bovine serum (Gibco), 4 % paraformaldehyde (PFA), and 4′,6-diamidino-2-phenylindole (DAPI; Vectashield) were acquired by ThermoFisher Scientific (Horsham, UK).

Aikaterini Dedeloudi, Fatima Farzeen, Vlad-Nicolae Lesutan, Robyn Irwin, Matthew P. Wylie, Sune Andersen, Mary Patrice Eastwood, Dimitrios A. Lamprou, Biopolymeric 3D printed scaffolds as a versatile tissue engineering treatment for congenital diaphragmatic hernia, International Journal of Pharmaceutics, Volume 672, 2025, 125313, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2025.125313.

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