Taoran Tian

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.

PCL-PEG-PCL film promotes cartilage regeneration in vivo.

Management of chondral defects has long been a challenge due to poor self‐healing capacity of articular cartilage. Many approaches, ranging from symptomatic treatment to structural cartilage regeneration, have obtained very limited satisfactory results. Cartilage tissue engineering, which involves optimized combination of novel scaffolds, cell sources and growth factors, has emerged as a promising strategy for cartilage regeneration and repair. In this study, the aim was to investigate the role of poly(ε‐caprolactone)‐poly(ethylene glycol)‐poly(ε‐caprolactone) (PCL‐PEG‐PCL, PCEC) PCEC scaffold in cartilage repair.

Angiogenesis in a 3D model containing adipose tissue stem cells and endothelial cells is mediated by canonical Wnt signaling

Adipose-derived stromal cells (ASCs) have gained great attention in regenerative medicine. Progress in our understanding of adult neovascularization further suggests the potential of ASCs in promoting vascular regeneration, although the specific cues that stimulate their angiogenic behavior remain controversial. In this study, we established a three-dimensional (3D) angiogenesis model by co-culturing ASCs and endothelial cells (ECs) in collagen gel and found that ASC-EC-instructed angiogenesis was regulated by the canonical Wnt pathway. Furthermore, the angiogenesis that occurred in implants collected after injections of our collagen gel-based 3D angiogenesis model into nude mice was confirmed to be functional and also regulated by the canonical Wnt pathway. Wnt regulation of angiogenesis involving changes in vessel length, vessel density, vessel sprout, and connection numbers occurred in our system. Wnt signaling was then shown to regulate ASC-mediated paracrine signaling during angiogenesis through the nuclear translocation of β-catenin after its cytoplasmic accumulation in both ASCs and ECs. This translocation enhanced the expression of nuclear co-factor Lef-1 and cyclin D1 and activated the angiogenic transcription of vascular endothelial growth factor A (VEGFA), basic fibroblast growth factor (bFGF), and insulin-like growth factor 1 (IGF-1). The angiogenesis process in the 3D collagen model appeared to follow canonical Wnt signaling, and this model can help us understand the importance of the canonical Wnt pathway in the use of ASCs in vascular regeneration.

Fabrication of Calcium Phosphate Microflowers and Their Extended Application in Bone Regeneration

The structure of materials is known to play an important role in material function. Nowadays, flowerlike structures have gained attention for studies not only in analytical chemistry, but also in biomaterial design. In this study, flowerlike structures were applied in bone regeneration in the form of calcium phosphate microflowers. The material was synthesized by a simple and environmentally friendly method. We characterized the structure and properties of the microflower using various methods. Cytotoxicity and osteogenesis-related gene regulations of the microflower were investigated in vitro. Cell uptake was observed by immunofluorescence. Rat calvarial critical-size defect models were successfully established to further confirm the enhanced bone regeneration ability of this material. We expect that this novel study will be of practical importance for the extended application of flowerlike materials and will provide new insights into the optimization of the morphology of calcium phosphate materials.

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.

Injectable and thermosensitive TGF-β1-loaded PCEC hydrogel system for in vivo cartilage repair

Chondral defects pose a great challenge for clinicians to manage owing to the limited capacity for self-healing. Various traditional approaches have been adopted for the repair of these defects with unsatisfactory results. Cartilage tissue engineering techniques have emerged as promising strategies to enhance regeneration and overcome these traditional shortcomings. The cell-homing based technique is considered the most promising owing to its unique advantages. Thermosensitive hydrogels have been applied as scaffolds for biomedical applications with smart sol–gel response for altering environmental temperature. Transforming growth factor (TGF)-β1 is considered to be capable of promoting chondrogenesis. In this study, a novel TGF-β1-loaded poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone) (PCEC) hydrogel was fabricated using simple procedures. Hydrogel characterization, rheological testing, component analysis, and assessment of sol–gel transition, in vitro degradation, and TGF-β1 release confirmed that this material possesses a porous microstructure with favorable injectability and sustained drug release. Full-thickness cartilage defects were induced on rat knees for in vivo cartilage repair for eight weeks. Micro-CT and histological evaluation provided further evidence of the optimal capacity of this novel hydrogel for cartilage regeneration with respect to that of other methods. Moreover, our results demonstrated that the cell-free hydrogel is thermosensitive, injectable, biodegradable, and capable of in vivo cartilage repair and possesses high potential and benefits for acellular cartilage tissue engineering and clinical application in the future.

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.