Recent advances in 3D-printed polylactide and polycaprolactone-based biomaterials for tissue engineering applications.

Tissue development, wound healing, pathogenesis, regeneration, and homeostasis rely upon coordinated and dynamic spatial and temporal remodeling of extracellular matrix (ECM) molecules. ECM reorganization and normal physiological tissue function, require the establishment and maintenance of biological, chemical, and mechanical feedback mechanisms directed by cell-matrix interactions. To replicate the physical and biological environment provided by the ECM in vivo, methods have been developed to decellularize and solubilize tissues which yield organ and tissue-specific bioactive hydrogels. While these biomaterials retain several important traits of the native ECM, the decellularizing process, and subsequent sterilization, and solubilization result in fragmented, cleaved, or partially denatured macromolecules. The final product has decreased viscosity, moduli, and yield strength, when compared to the source tissue, limiting the compatibility of isolated decellularized ECM (dECM) hydrogels with fabrication methods such as extrusion bioprinting. This review describes the physical and bioactive characteristics of dECM hydrogels and their role as biomaterials for biofabrication. In this work, critical variables when selecting the appropriate tissue source and extraction methods are identified. Common manual and automated fabrication techniques compatible with dECM hydrogels are described and compared. Fabrication and post-manufacturing challenges presented by the dECM hydrogels decreased mechanical and structural stability are discussed as well as circumvention strategies. We further highlight and provide examples of the use of dECM hydrogels in tissue engineering and their role in fabricating complex in vitro 3D microenvironments.

Decellularized ECM hydrogels: prior use considerations, applications, and opportunities in tissue engineering and biofabrication.

Extracellular matrix (ECM)-based bioinks has attracted much attention in recent years for 3D printing of native-like tissue constructs. Due to organ unavailability, human placental ECM can be an alternative source for the construction of 3D print composite scaffolds for the treatment of deep wounds. In this study, we use different concentrations (1.5%, 3% and 5%w/v) of ECM derived from the placenta, sodium-alginate and gelatin to prepare a printable bioink biomimicking natural skin. The printed hydrogels' morphology, physical structure, mechanical behavior, biocompatibility, and angiogenic property are investigated. The optimized ECM (5%w/v) 3D printed scaffold is applied on full-thickness wounds created in a mouse model. Due to their unique native-like structure, the ECM-based scaffolds provide a non-cytotoxic microenvironment for cell adhesion, infiltration, angiogenesis, and proliferation. In contrast, they do not show any sign of immune response to the host. Notably, the biodegradation, swelling rate, mechanical property, cell adhesion and angiogenesis properties increase with the increase of ECM concentrations in the construct. The ECM 3D printed scaffold implanted into deep wounds increases granulation tissue formation, angiogenesis, and re-epithelialization due to the presence of ECM components in the construct, when compared with printed scaffold with no ECM and no treatment wound. Overall, our findings demonstrate that the 5% ECM 3D scaffold supports the best deep wound regeneration in vivo, produces a skin replacement with a cellular structure comparable to native skin. 

https://doi.org/10.1016/j.mtbio.2023.100666

3D-printed placental-derived bioinks for skin tissue regeneration with improved angiogenesis and wound healing properties

Alginate sulfate/ECM composite hydrogel containing electrospun nanofiber with encapsulated human adipose-derived stem cells for cartilage tissue engineering.

Attempts are being made to develop an ideal wound dressing with excellent biomechanical and biological properties. Here, a thermos-responsive hydrogel is fabricated using chitosan (CTS) with various concentrations (1%, 2.5%, and 5% w/v) of solubilized placental extracellular matrix (ECM) and 20% β-glycerophosphate to optimize a smart wound dressing hydrogel with improved biological behavior. The thermo-responsive CTS (TCTS) alone or loaded with ECMs (ECM-TCTS) demonstrate uniform morphology using SEM. TCTS and ECM1%-TCTS and ECM2.5%-TCTS show a gelation time of 5 min at 37°C, while no gel formation was observed at 4°C and 25°C. ECM5%-TCTS formed gel at both 25°C and 37°C. The degradation and swelling ratios increase as the ECM content of the hydrogel increase. All the constructs show excellent biocompatibility in vitro and in vivo, however, the hydrogels with a higher concentration of ECM demonstrate better cell adhesion for fibroblast cells and induce expression of angiogenic factors (VEGF and VEGFR) from HUVEC. Only the ECM5%-TCTS has antibacterial activity against Acinetobacter baumannii ATCC 19606. The data obtained from the current study suggest the ECM2.5%-TCTS as an optimized smart biomimetic wound dressing with improved angiogenic properties now promises to proceed with pre-clinical and clinical investigations. This article is protected by copyright. All rights reserved.

Chitosan-placental ECM composite thermos-responsive hydrogel as a biomimetic wound dressing with angiogenic property.

Various composite scaffolds with different fabrication techniques have been applied in cartilage tissue engineering. In this study, poly ɛ-caprolactone (PCL) was printed by fused deposition modeling method, and the prepared scaffold was filled with Alginate (Alg): Alginate-Sulfate (Alg-Sul) hydrogel to provide a better biomimetic environment and emulate the structure of glycosaminoglycans properly. Furthermore, to enhance chondrogenesis, different concentrations of decellularized extracellular matrix (dECM) were added to the hydrogel. For cellular analyses, the adipose-derived mesenchymal stem cells were seeded on the hydrogel and the results of MTT assay, live/dead staining, and SEM images revealed that the scaffold with 1% dECM had better viscosity, cell viability, and proliferation. The study was conducted on the optimized scaffold (1% dECM) to determine mechanical characteristics, chondrogenic differentiation, and results demonstrated that the scaffold showed mechanical similarity to the native nasal cartilage tissue along with possessing appropriate biochemical features, which makes this new formulation based on PCL/dECM/Alg:Alg-Sul a promising candidate for further in-vivo studies.

An additive manufacturing-based 3D printed poly ɛ-caprolactone/alginate sulfate/extracellular matrix construct for nasal cartilage regeneration.

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An additive manufacturing-based 3D printed poly ɛ-caprolactone/alginate sulfate/extracellular matrix construct for nasal cartilage regeneration.