Decellularized extracellular matrix-based composite scaffolds for tissue engineering and regenerative medicine

Abstract

Despite the considerable advancements in fabricating polymeric-based scaffolds for tissue engineering, the clinical transformation of these scaffolds remained a big challenge because of the difficulty of simulating native organs/tissues' microenvironment. As a kind of natural tissue-derived biomaterials, decellularized extracellular matrix (dECM)-based scaffolds have gained attention due to their unique biomimetic properties, providing a specific microenvironment suitable for promoting cell proliferation, migration, attachment and regulating differentiation. The medical applications of dECM-based scaffolds have addressed critical challenges, including poor mechanical strength and insufficient stability. For promoting the reconstruction of damaged tissues or organs, different types of dECM-based composite platforms have been designed to mimic tissue microenvironment, including by integrating with natural polymer or/and syntenic polymer or adding bioactive factors. In this review, we summarized the research progress of dECM-based composite scaffolds in regenerative medicine, highlighting the critical challenges and future perspectives related to the medical application of these composite materials.

Keywords: bioactive factors; composites; decellularized extracellular matrix; polymer; tissue engineering.

Graphical abstract

Figure 1.

Compositions and applications of dECM-based composite scaffolds for tissue engineering.

Figure 2.

(A, B) SEM images of PCL and PCL-MECM scaffolds. (C, D) Biomechanical assessment. (E) SEM images of meniscal fibrochondrocytes after 3 days on various scaffolds. Adapted with permission from Ref. [43].

Figure 3.

(A, B) Stress–strain curve and compressive modulus values of PLGA-DSC and DSC scaffolds. (C, D) H&E staining images of the SCI area at 7 days after implantation. (E) High-magnification H&E staining images of PLGA-DSC and (F) DSC scaffolds. (G) Immunostaining images of the PLGA-DSC and (H) DSC scaffolds. (I) The quantification of α-SMA staining density. Adapted with permission from Ref. [52].

Figure 4.

Schematic illustrations and results of the hybrid hydrogel applied onto corneal defect in situ for long-term regenerative repair. Adapted with permission from Ref. [77].

Figure 5.

(A) The immunohistochemistry staining, (B) the semiquantitative analysis of COL-II after culturing BMSC on various scaffolds. Quantitative determination of (C) GAG and (D) DNA. The chondrogenic genes expression of (E) COL-II, (F) SOX 9, (G) AGG and (H) COL X. Adapted with permission from Ref. [108].

Figure 6.

(A) Schematic diagram showing the fabrication of hydrogel microspheres functionalized with dental pulp dECM and their application in regenerative endodontic treatment. (B, C) Dentin phosphophorym immunofluorescence analysis of hDPSCs. (D, E) Odontogenic-related gene mRNA expression levels. Adapted with permission from Ref. [131].

Figure 7.

(A) Schematic illustration of a vascular graft implanted into the descending abdominal aortas of Sprague–Dawley rats. (B) Color doppler ultrasound images after implantation. (C) The patency analysis. (D) SEM and CD31 immunofluorescent staining images of the luminal surface of the vascular grafts. Adapted with permission from Ref. [149].

Figure 8.

(A) Representative macroscopic images of the repaired tissues. (B) Macroscopic total scores, (C) macroscopic color, (D) defect filling (E) and macroscopic surface at 6 months. (F) Macroscopic total scores, (G) macroscopic color, (H) defect filling and (I) macroscopic surface at 12 months. Adapted with permission from Ref. [165].

Figure 9.

(A) Representative optical images of the zone of inhibition against bacteria. (B) Quantitative analysis of zone of inhibition. (C) Confocal images of the rBMSC cells. (D) The rBMSCs viability in different scaffolds. Adapted with permission from Ref. [175].

Figure 10.

(A) An overview illustrating 3D-printed different scaffolds implanted in rat knee osteochondral defects. (B) Representative MRI images. (C) Representative 3D reconstructed micro-CT images at defect sites. Quantitative analysis of (D) bone volume/total volume, (E) trabecular number and (F) trabecular thickness for regenerated bone tissues in the defects. Adapted with permission from Ref. [217].