Biomimetic Trachea Regeneration Using a Modular Ring Strategy Based on Poly(Sebacoyl Diglyceride)/Polycaprolactone for Segmental Trachea Defect Repair

Nerve tissue engineering is one of the most promising methods to restore nerve systems in human health care. Scaffold design has pivotal role in nerve tissue engineering. Polymer blending is one of the most effective methods for providing new, desirable biocomposites for tissue-engineering applications. Random and aligned PCL/gelatin biocomposite scaffolds were fabricated by varying the ratios of PCL and gelatin concentrations. Chemical and mechanical properties of PCL/gelatin nanofibrous scaffolds were measured by FTIR, porometry, contact angle and tensile measurements, while the in vitro biodegradability of the different nanofibrous scaffolds were evaluated too. PCL/gelatin 70:30 nanofiber was found to exhibit the most balanced properties to meet all the required specifications for nerve tissue and was used for in vitro culture of nerve stem cells (C17.2 cells). MTS assay and SEM results showed that the biocomposite of PCL/gelatin 70:30 nanofibrous scaffolds enhanced the nerve differentiation and proliferation compared to PCL nanofibrous scaffolds and acted as a positive cue to support neurite outgrowth. It was found that the direction of nerve cell elongation and neurite outgrowth on aligned nanofibrous scaffolds is parallel to the direction of fibers. PCL/gelatin 70:30 nanofibrous scaffolds proved to be a promising biomaterial suitable for nerve regeneration.

Abstract Biomacromolecules with poor mechanical properties cannot satisfy the stringent requirement for load‐bearing as bioscaffolds. Herein, a biodegradable high‐strength supramolecular polymer strengthened hydrogel composed of cleavable poly(N‐acryloyl 2‐glycine) (PACG) and methacrylated gelatin (GelMA) (PACG‐GelMA) is successfully constructed by photo‐initiated polymerization. Introducing hydrogen bond‐strengthened PACG contributes to a significant increase in the mechanical strengths of gelatin hydrogel with a high tensile strength (up to 1.1 MPa), outstanding compressive strength (up to 12.4 MPa), large Young's modulus (up to 320 kPa), and high compression modulus (up to 837 kPa). In turn, the GelMA chemical crosslinking could stabilize the temporary PACG network, showing tunable biodegradability by adjusting ACG/GelMA ratios. Further, a biohybrid gradient scaffold consisting of top layer of PACG‐GelMA hydrogel‐Mn2+ and bottom layer of PACG‐GelMA hydrogel‐bioactive glass is fabricated for repair of osteochondral defects by a 3D printing technique. In vitro biological experiments demonstrate that the biohybrid gradient hydrogel scaffold not only supports cell attachment and spreading but also enhances gene expression of chondrogenic‐related and osteogenic‐related differentiation of human bone marrow stem cells. Around 12 weeks after in vivo implantation, the biohybrid gradient hydrogel scaffold significantly facilitates concurrent regeneration of cartilage and subchondral bone in a rat model.

Microtia is a congenital external ear malformation that can seriously influence the psychological and physiological well-being of affected children. The successful regeneration of human ear-shaped cartilage using a tissue engineering approach in a nude mouse represents a promising approach for auricular reconstruction. However, owing to technical issues in cell source, shape control, mechanical strength, biosafety, and long-term stability of the regenerated cartilage, human tissue engineered ear-shaped cartilage is yet to be applied clinically. Using expanded microtia chondrocytes, compound biodegradable scaffold, and in vitro culture technique, we engineered patient-specific ear-shaped cartilage in vitro. Moreover, the cartilage was used for auricle reconstruction of five microtia patients and achieved satisfactory aesthetical outcome with mature cartilage formation during 2.5 years follow-up in the first conducted case. Different surgical procedures were also employed to find the optimal approach for handling tissue engineered grafts. In conclusion, the results represent a significant breakthrough in clinical translation of tissue engineered human ear-shaped cartilage given the established in vitro engineering technique and suitable surgical procedure. This study was registered in Chinese Clinical Trial Registry (ChiCTR-ICN-14005469).