Quanquan Ma

The fabrication of biomimetic biphasic CAN-PAC hydrogel with a seamless interfacial layer applied in osteochondral defect repair

Cartilage tissue engineering based on biomimetic scaffolds has become a rapidly developing strategy for repairing cartilage defects. In this study, a biphasic CAN-PAC hydrogel for osteochondral defect (OCD) regeneration was fabricated based on the density difference between the two layers via a thermally reactive, rapid cross-linking method. The upper hydrogel was cross-linked by CSMA and NIPAm, and the lower hydrogel was composed of PECDA, AAm and PEGDA. The interface between the two layers was first grafted by the physical cross-linking of calcium gluconate and alginate, followed by the chemical cross-linking of the carbon-carbon double bonds in the other components. The pore sizes of the upper and lower hydrogels were ~187.4 and ~112.6 μm, respectively. The moduli of the upper and lower hydrogels were ~0.065 and ~0.261 MPa. This prepared bilayer hydrogel exhibited the characteristics of mimetic composition, mimetic structure and mimetic stiffness, which provided a microenvironment for sustaining cell attachment and viability. Meanwhile, the biodegradability and biocompatibility of the CAN-PAC hydrogel were examined in vivo. Furthermore, an osteochondral defect model was developed in rabbits, and the bilayer hydrogels were implanted into the defect. The regenerated tissues in the bilayer hydrogel group exhibited new translucent cartilage and repaired subchondral bone, indicating that the hydrogel can enhance the repair of osteochondral defects.

Curved microstructures promote osteogenesis of mesenchymal stem cells via the RhoA/ROCK pathway.

Cells in the osteon reside in a curved space, accordingly, the curvature of the microenvironment is an important geometric feature in bone formation. However, it is not clear how curved microstructures affect cellular behaviour in bone tissue.

Anti-inflammatory and Antioxidative Effects of Tetrahedral DNA Nanostructures via the Modulation of Macrophage Responses

Tetrahedral DNA nanostructures (TDNs) are a new type of nanomaterials that have recently attracted attention in the field of biomedicine. However, the practical application of nanomaterials is often limited owing to the host immune response. Here, the response of RAW264.7 macrophages to TDNs was comprehensively evaluated. The results showed that TDNs had no observable cytotoxicity and could induce polarization of RAW264.7 cells to the M1 type. TDNs attenuated the expression of NO IL-1β (interleukin-1β), IL-6 (interleukin-6), and TNF-α (tumor necrosis factor-α) in LPS-induced RAW264.7 cells by inhibiting MAPK phosphorylation. In addition, TDNs inhibited LPS-induced reactive oxygen species (ROS) production and cell apoptosis by up-regulating the mRNA expression of antioxidative enzyme heme oxygenase-1 (HO-1). The findings of this study demonstrated that TDNs have great potential as a novel theranostic agent because of their anti-inflammatory and antioxidant activities, high bioavailability, and ease of targeting.

Electrospun Poly (3-Hydroxybutyrate-Co-4-Hydroxybutyrate)/Graphene Oxide Scaffold: Enhanced Properties and Promoted in Vivo Bone Repair in Rats

Bone tissue engineering emerges as an advantageous technique to achieve tissue regeneration. Its scaffolds must present excellent biomechanical properties, where bare polymers poorly perform. Development of new biomaterials with high osteogenic capacity is urgently pursued. In this study, an electrospun poly(3-hydroxybutyrate-co-4-hydroxybutyrate)/graphene oxide (P34HB/GO) nanofibrous scaffold is successfully fabricated and characterized. The effects of GO amount on scaffold morphology, biomechanical properties, and cellular behaviors are investigated. GO reduces the fiber diameter and enhances porosity, hydrophilicity, mechanical properties, cellular performance, and osteogenic differentiation of scaffolds. P34HB/GO triumphs over P34HB in in vivo bone regeneration in critical-sized calvarial defect of rats. We believe that this study is the first to evaluate the capability of in vivo bone repair of electrospun P34HB/GO scaffold. With facile fabrication process, favorable porous structures, enhanced biomechanical properties, and fast osteogenic capability, P34HB/GO scaffold holds practical potentials for bone tissue engineering application.

Effect of Tetrahedral DNA Nanostructures on Proliferation and Osteo/Odontogenic Differentiation of Dental Pulp Stem Cells via Activation of the Notch Signaling Pathway

Dental pulp stem cells (DPSCs) derived from the human dental pulp tissue have multiple differentiation capabilities, such as osteo/odontogenic differentiation. Therefore, DPSCs are deemed as ideal stem cell sources for tissue regeneration. As new nanomaterials based on DNA, tetrahedral DNA nanostructures (TDNs) have tremendous potential for biomedical applications. Here, the authors aimed to explore the part played by TDNs in proliferation and osteo/odontogenic differentiation of DPSCs, and attempted to investigate if these cellular responses could be driven by activating the canonical Notch signaling pathway. Upon exposure to TDNs, proliferation and osteo/odontogenic differentiation of DPSCs were dramatically enhanced, accompanied by up regulation of Notch signaling. In general, our study suggested that TDNs can significantly promote proliferation and osteo/odontogenic differentiation of DPSCs, and this remarkable discovery can be applied in tissue engineering and regenerative medicine to develop a significant and novel method for bone and dental tissue regeneration.

Stiffness regulates the proliferation and osteogenic/odontogenic differentiation of human dental pulp stem cells via the WNT signalling pathway

Researches showed that stiffness of the extracellular matrix can affect the differentiation of many stem cells. Dental pulp stem cells (DPSCs) are a promising type of adult stem cell. However, we know little about whether and how the behaviour of DPSCs is influenced by stiffness.

Hypoxia triggers angiogenesis by increasing expression of LOX genes in 3-D culture of ASCs and ECs

Objectives: This study aimed to investigate the expression changes of LOX (lysyl oxidase) family genes, VEGFA, and VEGFB under hypoxic conditions in a co‐culture system of ASCs (adipose‐derived stromal cells) and ECs (endothelial cells). Materials and methods: ASCs and ECs were co‐cultured under hypoxic and normal oxygen conditions in a 1:1 ratio, and the formation of vessel‐like was detected at 7 days. The transwell co‐culture system was used and cell lysates were collected at 7 days after co‐culture in hypoxic and normal oxygen condition. Semi‐quantitative PCR was performed to quantify the mRNA expression of VEGFA, VEGFB, and the LOX genes (LOX, LOXL‐1, LOXL‐2, LOXL‐3, and LOXL‐4). Expression changes were determined by densitomery. Results: Enhanced angiogenesis was detected in the co‐culture of ASCs and ECs under hypoxic conditions. Among the genes screened, VEGFA, VEGFB, LOXL‐1, and LOXL‐3 in ECs, both mono‐cultured and co‐cultured, were significantly enhanced after culturing under hypoxic conditions. In ASCs, VEGFB, LOXL‐1, and LOXL‐3 were upregulated. Conclusions: Contact co‐culture between ASCs and ECs promotes angiogenesis under hypoxia. LOXL‐1 and LOXL‐3 expressions were increased in both ASCs and ECs and might play important roles in the enhanced angiogenesis promoted by hypoxia. HIGHLIGHTSLOX, LOXL‐1, and LOXL‐3 may play important roles in angiogenesis triggered by hypoxia.This finding will help us acknowledge the role of the LOX family in tumor tissues.This finding may help in solving some clinical problems, especially in tumor therapy and regenerative medicine.The exact mechanism of angiogenesis promotion by hypoxia through enhancing LOX expression still needs further exploration.

Effect of substrate stiffness on proliferation and differentiation of periodontal ligament stem cells

The aim of this study was to understand the effect of substrate stiffness (a mechanical factor of the extracellular matrix) on periodontal ligament stem cells (PDLSCs) and its underlying mechanism.

Application of Stem Cells and the Factors Influence Their Differentiation in Cartilage Tissue Engineering

Articular cartilage is a unique tissue which contents only one cell type and lack the ability to heal spontaneously. Current treatment for cartilage defects include non-operative treatment, traditional operative treatment and the cartilage tissue engineering. Among these treatments cartilage tissue engineering have drawn attention to the scientists in recent years. Standard tissue engineering requires three factors: seed cells, scaffold and growth factors. Mature chondrocytes were first used as a seed cell in cartilage tissue engineering. While stem cells, however, have become a new candidate for cartilage tissue engineering. Main sources of stem cell in cartilage tissue engineering consist of embryonic stem cells (ESCs), mesenchymal stem cells (MSCs) and other kinds of stem cells.

Reconstruction of Mandible: A Fully Digital Workflow From Visualized Iliac Bone Grafting to Implant Restoration

PURPOSE Although digital aids can help surgeons compensate for the shortcomings of traditional mandibular reconstruction techniques to perform surgery more precisely and effectively, the use of these digital techniques has often been fragmented, divided, and incomplete. This article describes the workflow of a fully digital mandibular reconstruction to explore the proper indications and discusses innovations based on the accuracy and effectiveness of digital techniques. MATERIALS AND METHODS A restoration-oriented mandibular reconstruction was performed by applying different digital techniques. Preoperative virtual surgery and rapid prototyping were used to aid the vascularized iliac bone graft surgery, which offered a solid basis for the ensuing treatment. Subsequently, implant rehabilitation was accomplished with the assistance of computer-assisted design and manufacture, laser treatment, and selective laser melting techniques. RESULT The workflow of the fully digital mandibular reconstruction successfully achieved a restoration-oriented treatment. These predictable, accurate, and effective digital techniques improved the consistency of pretreatment design and follow-up treatment. The treatment sequence achieved high predictability and reproducibility owing to the use of digital techniques. CONCLUSION This study shows that a digital workflow can be predictable, accurate, and effective, which suggests that it could be a valid digital protocol for developing a treatment sequence for patients with jaw defects caused by trauma, congenital anomalies, or mandibular tumor resection.