Stem Cell-Laden Hydrogel-Based 3D Bioprinting for Bone and Cartilage Tissue Engineering

Abstract

Tremendous advances in tissue engineering and regenerative medicine have revealed the potential of fabricating biomaterials to solve the dilemma of bone and articular defects by promoting osteochondral and cartilage regeneration. Three-dimensional (3D) bioprinting is an innovative fabrication technology to precisely distribute the cell-laden bioink for the construction of artificial tissues, demonstrating great prospect in bone and joint construction areas. With well controllable printability, biocompatibility, biodegradability, and mechanical properties, hydrogels have been emerging as an attractive 3D bioprinting material, which provides a favorable biomimetic microenvironment for cell adhesion, orientation, migration, proliferation, and differentiation. Stem cell-based therapy has been known as a promising approach in regenerative medicine; however, limitations arise from the uncontrollable proliferation, migration, and differentiation of the stem cells and fortunately could be improved after stem cells were encapsulated in the hydrogel. In this review, our focus was centered on the characterization and application of stem cell-laden hydrogel-based 3D bioprinting for bone and cartilage tissue engineering. We not only highlighted the effect of various kinds of hydrogels, stem cells, inorganic particles, and growth factors on chondrogenesis and osteogenesis but also outlined the relationship between biophysical properties like biocompatibility, biodegradability, osteoinductivity, and the regeneration of bone and cartilage. This study was invented to discuss the challenge we have been encountering, the recent progress we have achieved, and the future perspective we have proposed for in this field.

Keywords: 3D bioprinting; bone; cartilage; hydrogel; stem cell.

FIGURE 1

Schematic illustration of 3D bioprinting of hydrogels scaffold for repair of bone and cartilage defect. Pre-processing: prepare a mixture using hydrogel, stem cells, and growth factors; bioprinting: successful 3D bioprinting of biomaterials with physiological cell density in a designed way; post-processing: crosslinking of bioprinted constructs by UV-ray.

FIGURE 2

Schematic images of (A) extrusion-based, (B) inkjet-based, (C) laser-assisted, and (D) stereolithography 3D bioprinting system. (A) Extrusion-based 3D bioprinting: extrusion bioprinters use pneumatics, piston, or screw force to continuously extrude a liquid cell-hydrogel solution. (B) Inkjet-based 3D bioprinting: the printer heads are deformed by a thermal or piezoelectric actuator and squeezed to generate droplets of a controllable size. (C) Laser-assisted 3D bioprinting: laser bioprinters use a laser to vaporize a region in the donor layer (top) forming a bubble that propels a suspended bioink to fall onto the substrate. (D) Stereolithography 3D bioprinting: stereolithographic printers use a digital UV or visible light projector to selectively cross-link bioinks plane-by-plane.

FIGURE 3

Mechanisms of osteogenesis and chondrogenesis. In bone remodeling sites, MSCs aggregate and form mesenchymal condensations. Then, bone is formed in two ways: intramembranous ossification and endochondral ossification. During the intramembranous ossification process, MSCs are differentiated into pre-osteoblasts, then they lost proliferation capacity and mature into osteoblasts, which secret alkaline phosphatase and osteocalcin that participate in the secretion, maturation, and mineralization of the extracellular matrix (ECM). In endochondral ossification, differentiated chondrocytes either proliferate in cartilage elements or exhibit hypertrophic maturation for subsequent endochondral ossification.

FIGURE 4

Current challenges and solutions for bone and cartilage tissue engineering.