Jinfeng Liao

Nanomaterials and bone regeneration

The worldwide incidence of bone disorders and conditions has been increasing. Bone is a nanomaterials composed of organic (mainly collagen) and inorganic (mainly nano-hydroxyapatite) components, with a hierarchical structure ranging from nanoscale to macroscale. In consideration of the serious limitation in traditional therapies, nanomaterials provide some new strategy in bone regeneration. Nanostructured scaffolds provide a closer structural support approximation to native bone architecture for the cells and regulate cell proliferation, differentiation, and migration, which results in the formation of functional tissues. In this article, we focused on reviewing the classification and design of nanostructured materials and nanocarrier materials for bone regeneration, their cell interaction properties, and their application in bone tissue engineering and regeneration. Furthermore, some new challenges about the future research on the application of nanomaterials for bone regeneration are described in the conclusion and perspectives part.

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.

The Effect of shape on Cellular Uptake of Gold Nanoparticles in the forms of Stars, Rods, and Triangles

Gold nanomaterials have attracted considerable interest as vehicles for intracellular drug delivery. In our study, we synthesized three different shapes of methylpolyethylene glycol coated-anisotropic gold nanoparticles: stars, rods, and triangles. The cellular internalization of these nanoparticles by RAW264.7 cells was analyzed, providing a parametric evaluation of the effect of shape. The efficiency of cellular uptake of the gold nanoparticles was found to rank in the following order from lowest to highest: stars, rods, and triangles. The possible mechanisms of cellular uptake for the three types of gold nanoparticles were examined, and it was found that different shapes tended to use the various endocytosis pathways in different proportions. Our study, which has demonstrated that shape can modulate the uptake of nanoparticles into RAW264.7 cells and that triangles were the shape with the most efficient cellular uptake, provides useful guidance toward the design of nanomaterials for drug delivery.

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.

Tea Polyphenol–Functionalized Graphene/Chitosan as an Experimental Platform with Improved Mechanical Behavior and Bioactivity

In this study, water-soluble, one-step highly reduced and functionalized graphene oxide was prepared via a facile, environment-friendly method by using tea polyphenol (TP), which acted as both reducing agent and stabilizer. The product obtained, that is, tea polyphenol-reduced graphene oxide (TPG), was used as a reinforcing building block for the modification of a mechanically weak chitosan (CS), TPG/CS. The morphology and physicochemical and mechanical properties of the composite were examined by various characterizations. The tensile strength and elastic modulus of CS were greatly improved by TPG, as compared to the findings for GO incorporation. Additionally, to our knowledge, this study is an in-depth analysis of the osteoblast functions of CS/TPG, including aspects such as cell cytotoxicity, proliferation, and expression of ossification genes, alkaline phosphatase (ALP), and Runt-related transcription factor (Runx2), which showed advantages in favorably modulating cellular activity. It was concluded that TPG/CS showed a higher elastic modulus, better hydrophilicity, and excellent biocompatibility than the pristine chitosan for promoting the proliferation and differentiation of osteoblasts, as well as for accelerating the expression of ALP and Runx2 (as shown by reverse transcription polymerase chain reaction (RT-PCR)). These results may provide new prospects for the use of TPG in the modification of biomaterials and for broadening the application of TPG in biological fields.

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.

The Research Advances of Nanomaterials Inducing Osteogenic and Chondrogenic Differentiation of Stem Cells

Nanomaterials because of their unique chemical and mechanic properties and biomimetic characteristics have attracted great attention in biomedicine and tissue engineering. Stem cells have the potential of multi-directional differentiation. Nanomaterials inducing osteogenic and chondrogenic differentiation of stem cells promotes the development of bone and cartilage tissue engineering. They are devided into inorganic nanomaterials and polymer nanomaterials. Each material has different effect in stem cell osteogenic and chondrogenic differentiation. Changing the size, shape and surface chemistry would generate new effects. Even more, they can achieve much enhanced osteochondral differentiation of stem cells through surface connected with bioactive molecules such as drugs, proteins and growth factors and incorporated into other nanomaterials. In this chapter, we list some extensive researched nanomaterials and focus on their influence in osteogenic and chondrogenic differentiation of stem cells.