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Table 2 Different types of lung scaffolds in regenerative medicine

From: Advancements in lung regeneration: from bench to bedside

Scaffolds origin

Stem cells/cells

Method

Outcome

Ref/year

Poly (vinylidene fluoride-co-tetrafluoroethylene) (P(VDFTrFE))/ZnO

Stem cell

A549 alveolar epithelial cells were seeded on scaffolds in the presence of lung-infecting bacteria

(in vitro)

Scaffolds have appropriate antibacterial activities, piezoelectricity, and good mechanical effects on the alveolar fibers and walls.

[67]/2020

Collagen, basic fibroblast growth factor (bFGF), colloidal crystal scaffolds (CCS)

TC-1

normal Beas-2B cells

Beas-2B cells and TC-1 were seeded with Scaffolds (in vitro)

Beas-2B and TC-1 cells viability elevated remarkably on collagen-bFGF-CCS

[68]/2019

Pig lung-trachea

-

Perfusion-decellularization

(chemical detergent)

Retained ECM

Maintaining 3D structure integrity.

[17]/2015

Pig lung

-

Perfusion-decellularization

with chemical procedure

This decellularization protocol prepares a reproducible and time-efficient method to produce an acellular scaffold.

[129]/2015

POSS-PCL

bmMSCs and HBECs

HBECs and bmMSCs were cultured on PCL- POSS for two weeks

A viable scaffold highly supports the attachment of bmMSC and HBEC

[64]/2015

Rat lung

-

Decellularizing the rat lung with chemical detergent

One single chemical detergent had a remarkable destruction.

So, the lung maintained in 3D, and the ECM proteins were lower.

[69]/2017

Rat lung

-

Decellularizing the rat lung with chemical detergent

During this procedure, the 3D structure of the lung and ECM had lower destruction.

[130]/2017

Rat lung

-

Decellularizing the rat lung with chemical detergent

Suitable scaffolds were produced for recellularization in all ex vivo and in vivo models

[16]/2019

Human Lung

-

Decellularizing the human lung by chemical detergent and recellularizing them

Replacement of targeted cells in extracorporeal organs is practical and causes chimeric organs to be appropriate for transplantation.

[73]/2019

Pig lung

-

Decellularizing the lung matrix by chemical detergent

The automated method suggested a more consistent matrix and decreased the decellularization process demanded time

[121]/2015

Mouse lungs

MSCS and alveolar type II cells (c10) derived from Bone marrow

MSCS and alveolar type II

Chemical detergents decellularized lungs; then they were reseeded.

Recellularizing the decellularized mouse lung in a bioreactor

Better regeneration

Lower apoptosis

[131]/2015

Gelatin

-

An enzyme-cross-linked gelatin scaffold was created by mixing surfactant with mTGase and mixing A549 cell suspension.

Microbubble scaffolds were so much like alveoli.

The response to the gemcitabine was the same as the clinical regimen for treating lung carcinoma.

[70]/2020

Collagen/hepatocyte

growth factor

Vascular endothelial and lung epithelial cells

A collagen scaffold seeded with vascular endothelial and lung epithelial cells

In a rat model

(in vivo).

This 3D collagen scaffold was so similar to that of the normal lung structure and helped alveolar regeneration in acute lung damage.

[74]/2020

Silk fibroin (SF)/2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)/oxidized bacterial

cellulose (OBC)

Human lung epithelial stem cells

Lung epithelial stem cells were seeded on SF-OBC hydrogel scaffolds.

The OBC nanofibril’s orientation along print lines prepared physical cues for guiding the lung epithelial stem cell’s orientation, which retained the ability to increase and maintain epithelial phenotype after seven days of culture.

[65]/2020

Pig lung

-

They decellularize the lung matrix using chemical detergent.

12 h pepsin digest of pig lung dECM (decellularized ECM) prepared an optimal stabilize between desirable physical ECM hydrogel activities and impacts on behaviors of lung cell

[63]/2020

Poly(urea-urethane)

(PUU) terminated by polyhedral oligomeric silsesquioxane (POSS)/Collagen

hBEpiCs/bmMSCs

hBEpiCs/bmMSCs are seeded on the scaffold.

bmMSCs in the co-culture system stimulated an overall matured physiological tissue analog of the respiratory system

[66]/2020

Collagen hyaluronic acid bilayered (CHyA-B)

Human embryonic lung fibroblast cell / Bronchial epithelial cell

Wi38 lung fibroblasts and Calu-3 bronchial epithelial cells were grown on either CHyA-B scaffold.

CHyA-B scaffolds facilitate the differentiation and growth of bronchial epithelial cells in a 3D co-culture model with various transepithelial resistance.

[71]/2021

Pig lung

-

They decellularize the pig lung matrix using chemical detergent.

MSCS implied appropriate viability, the existence of cell-matrix interactions in the scaffolds, and adhesion ability and focal adhesions length formed were raised for the cells cultured within the lung hydrogel scaffolds

[72]/2021

Rat lung

-

Decellularizing the rat lung with chemical detergent

Controlled EDC/NHS crosslinking could be prepared with mechanical effects as the same native lung, which promotes mesenchymal lung cell proliferation and does not promote the immune system of the recipient more than a non-cross-linked tissue

[3]/2021

Pig lung

Human endothelial cells

Decellularizing the pig lung by chemical detergent

Seeding them with human airway epithelial PGs

Bioengineered lung grafts could tolerate physiological blood flow from the pulmonary circulation of the recipient and exchange gases upon ventilation during an hour-long study.

[75]/2018

Pig lung

-

Perfusion-decellularization

(chemical detergent)

The optimal cocktail method contains dextrose /SLES/Triton X-100, which can be utilized for the decellularization of entire pig cell lung to acquire bioengineered scaffolding on a clinical scale.

[62]/2021

Decellularized lung scaffolds

Alveolar epithelial type 2 cell (AEC2)

To direct AEC2 behavior for epithelial regeneration, researchers altered multimodal elements of the alveolar epithelial type 2 cell (AEC2) niche in decellularized lung scaffolds.

The results show how to create an epithelium with AEC2s and AEC1s arranged in alveolar-like units with endothelial, mesenchymal, and epithelial components methodically. They highlight the critical interplay between biochemical, mechanical, and cellular signals in the alveolus’s reconstruction.

[132]/2023

An artificial three-dimensional (3D) biomimetic scaffold

Umbilical cord mesenchymal-derived stem cells (UC-MSCs)

In order to give endogenous stem cells a favorable regeneration niche for in situ lung regeneration, researchers developed an artificial three-dimensional (3D) biomimetic scaffold-based MSC implant.

The combination of MSC implants and artificial 3D biomimetic scaffolds promotes in situ lung regeneration and eases the healing process after lung damage, providing a potential direction for tissue engineering and stem cell therapies in lung regeneration.

[133]/2023

Porcine-decellularized lung scaffolds

Human airway epithelial cells and human umbilical vein endothelial cells

Human airway epithelial cells and human umbilical vein endothelial cells were introduced onto porcine decellularized lung scaffolds.

In a swine model, the engineering and orthotopic implantation of bioartificial lungs using human cells were technically possible, exhibiting preliminary gas exchange performance. However, continuous efforts are needed to improve the grafts’ recellularization and maturation to maintain perfusion and functionality.

[134]/2022

Sheep lung dECM-derived scaffold.

Human embryonic stem cells (hESCs)-derived definitive endoderm (DE) into lung progenitor cells

Researchers assess how the scaffold formed from sheep lung dECM affects the differentiation and subsequent maturation of lung progenitor cells obtained from ESCs.

Compared to dECM-derived hydrogel and fibronectin-coated plates, the differentiation of DE cells towards lung alveolar progenitor cells is enhanced by the dECM-derived scaffold.

[135]/2023