No abstract

Three-dimensional (3D) printing provides a new approach of fabricating implantable products because it permits a flexible manner to extrude complex and customized shapes of the tissue scaffolds. Compared with other printable biomaterials, the polyurethane elastomer has several merits, including excellent mechanical properties and good biocompatibility. However, some intrinsic behavior, especially its high melting point and slow rate of degradation, hampered its application in 3D printed tissue engineering. Herein, we developed a 3D printable amino acid modified biodegradable waterborne polyurethane (WBPU) using a water-based green chemistry process. The flexibility of this material endows better compliance with tissue during implantation and prevents high modulus transplants from scratching surrounding tissues. The histocompatibility experiments show that the WBPU induces no apparent acute rejection or inflammation in vivo. We successfully fabricated a highly flexible WBPU scaffold by deposition 3D printing technology at a low temperature (50°C ~ 70 °C), and the printed products could support the adhesion and proliferation of chondrocytes and fibroblasts. The printed blocks possessed controllable degradability due to the different amounts of hydrophilic chain extender and did not cause accumulation of acidic products. In addition, we demonstrated that our WBPU is highly applicable for implantable tissue engineering because there is no cytotoxicity during its degradation. Taken together, we envision that this printable WBPU can be used as an alternative biomaterial for tissue engineering with low temperature printing, biodegradability, and compatibility.

Tissue-engineered ear cartilage scaffold based on three-dimensional (3D) bioprinting technology presents a new strategy for ear reconstruction in individuals with microtia. Natural hydrogel is a promising material due to its excellent biocompatibility and low immunogenicity. However, insufficient mechanical property required for cartilage is one of the major issues pending to be solved. In this study, the gelatin methacryloyl (GelMA) hydrogel reinforced with bacterial nanocellulose (BNC) was developed to enhance the biomechanical properties and printability of the hydrogel. The results revealed that the addition of 0.375% BNC significantly increased the mechanical properties of the hydrogel and promoted cell migration in the BNC-reinforced hydrogel. Constructs bioprinted with chondrocyte-laden BNC/GelMA hydrogel bio-ink formed mature cartilage in nude mice with higher Young’s modulus and glycosaminoglycan content. Finally, an auricle equivalent with a precise shape, high mechanics, and abundant cartilage-specific matrix was developed in vivo. In this study, we developed a potentially useful hydrogel for the manufacture of auricular cartilage grafts for microtia patients.

Large-scale skin injuries are usually accompanied by impaired wound healing, resulting in scar formation, or significant morbidity and mortality. The aim of this study is to explore the in vivo application of 3D-printed tissue-engineered skin substitute using innovative biomaterial loaded with human adipose-derived stem cells (hADSCs) in wound healing. Adipose tissue was decellularized, and extracellular matrix components were lyophilized and solubilized to obtain adipose tissue decellularized extracellular matrix (dECM) pre-gel. The newly designed biomaterial is composed of adipose tissue dECM pre-gel, methacrylated gelatin (GelMA), and methacrylated hyaluronic acid (HAMA). Rheological measurement was performed to evaluate the phase-transition temperature and the storage and loss modulus at this temperature. Tissue-engineered skin substitute loaded with hADSCs was fabricated by 3D printing. We used nude mice to establish full-thickness skin wound healing model and divided them into four groups randomly: (A) Full-thickness skin graft treatment group, (B) 3D-bioprinted skin substitute treatment group as the experimental group, (C) microskin graft treatment group, and (D) control group. The amount of DNA in each milligram of dECM was 24.5 ± 7.1 ng, fulfilling the currently accepted decellularization criteria. The solubilized adipose tissue dECM was thermo-sensitive biomaterial and underwent a sol-gel phase transition when temperature rises. The dECM-GelMA-HAMA precursor undergoes a gel-sol phase transition at 17.5°C, where the storage and loss modulus of the precursor is about 8 Pa. The scanning electron microscope showed that the interior of crosslinked dECM-GelMA-HAMA hydrogel is 3D porous network structure with suitable porosity and pore size. The shape of the skin substitute is stable with regular grid-like scaffold structure. Wound healing in the experimented animals was accelerated after being treated with 3D-printed skin substitute, which attenuate inflammatory response, increase blood perfusion around the wound, as well as promote re-epithelialization, collagen deposition and alignment, and angiogenesis. In summary, 3D-printed dECM-GelMA-HAMA tissue-engineered skin substitute loaded with hADSCs, which can be fabricated by 3D printing, can accelerate wound healing and improve healing quality by promoting angiogenesis. The hADSCs and the stable 3D-printed stereoscopic grid-like scaffold structure play a critical role in promoting wound healing.