Current Stem Cell Research & Therapy - Volume 13, Issue 7, 2018

Hydrogels are degradable polymeric networks, in which cross-links play a vital role in structure formation and degradation. Cross-linking is a stabilization process in polymer chemistry that leads to the multi-dimensional extension of polymeric chains, resulting in network structures. By crosslinking, hydrogels are formed into stable structures that differ from their raw materials. Generally, hydrogels can be prepared from either synthetic or natural polymers. Based on the types of cross-link junctions, hydrogels can be categorized into two groups: the chemically cross-linked and the physically cross-linked. Chemically cross-linked gels have permanent junctions, in which covalent bonds are present between different polymer chains, thus leading to excellent mechanical strength. Although chemical cross-linking is a highly resourceful method for the formation of hydrogels, the cross-linkers used in hydrogel preparation should be extracted from the hydrogels before use, due to their reported toxicity, while, in physically cross-linked gels, dissolution is prevented by physical interactions, such as ionic interactions, hydrogen bonds or hydrophobic interactions. Physically cross-linked methods for the preparation of hydrogels are the alternative solution for cross-linker toxicity. Both methods will be discussed in this review.

Background: Cartilage has limited ability for self-repairing, prompting the search for cartilage substitutes that can repair cartilage defects. Hydrogels have attracted attention as cartilage substitutes, since their mechanical properties, swelling ability and lubricating behavior are similar to extracellular matrix of articular cartilage. Hydrogels can be of natural, synthetic or hybrid origin, and hydrogels can encapsulate stem cells and/or be loaded with growth factors to promote cell differentiation into a chondrogenic phenotype. Objective and Results: This review summarizes basic research advances in using hydrogels to repair cartilage defects. The raw materials, stem cells and growth factors used to prepare hydrogels are discussed. Conclusion: Substantial success has been achieved in small animal models of cartilage repair and regeneration, but further research is needed to improve hydrogels' mechanical properties and their integration with surrounding tissues.

Local cartilage or osteochondral lesions are painful and harmful. Besides pain and limited function of joints, cartilage defect is considered as one of the leading extrinsic risk factors for osteoarthritis (OA). Thus, clinicians and scientists have paid great attention to regenerative therapeutic methods for the early treatment of cartilaginous defects. Regenerative medicine, showing great hope for regenerating cartilage tissue, relies on the combination of biodegradable scaffolds and particular biological factors, such as growth factors, genetic cues. Among all biomaterials, hydrogels have become a promising type of scaffolds for simultaneous cell growth and drug delivery in cartilage tissue engineering. A wide range of animal models have been applied in testing repair with hydrogels in cartilage defects. This review summarized the current animal models used to test hydrogels technologies for the regeneration of cartilage. Advantages and disadvantages in the establishment of the cartilage defect animal models among different species were emphasized, as well as the feasibility of replication of diseases in animals.

Cartilage, constituted with a relatively hypocellular structure and lacking of neural and vascular connections, is not a well self-repairing tissue. Cartilage tissue engineering involving bulk of biomaterials has been put forward as a strategy for articular cartilage lesions. The most complicated issue for cartilage repairing is to simulate the highly hierarchical structure, extracellular matrix (ECM) composition and even mechanical features. Electrospinning can produce flexible, dense fibrous membranes with moderate mechanical properties and biological features with different constitution of polymer, orientation, diameter and morphology of fibers, or cooperation forms with other strategies. In our review, four classes are mentioned for cartilage tissue engineering and kinds of biomaterials to be utilized.

Cartilage tissue engineering is emerging as a therapeutic approach for the repair and regeneration of cartilage tissue defects resulting from trauma and disease. It is still essential to explore approaches that employ combinations of ideal seed cells, biomaterials, and growth factors to repair defect areas because cartilage lacks spontaneous regenerative capabilities and traditional treatments do not fully satisfy clinical requirements. The purpose of this review is to summarize key advances in this area with an emphasis on adult stem cells because these cells possess a self-renewal ability and the potential for multi-directional differentiation when cultured under appropriate conditions, such as chondrocyte differentiation to synthesize cartilage-specific matrix proteins. Additionally, hydrogels and their synergistic action with growth factors to co-regulate cell behaviors and cartilage regeneration will be addressed. Hydrogels are three-dimensional water-swollen networks that provide a unique microenvironment to promote the chondrogenic phenotype by encapsulating cells as a functional cartilage substitute in a defect area. Ultimately, this review presents the prospect of combining adult stem cells, hydrogels, and growth factors using interdisciplinary approaches that may lead to significant breakthroughs in cartilage regeneration in the future.

Cartilage tissue engineering is an emerging technique for the regeneration of cartilage tissue damaged as a result of trauma or disease. As the propensity for healing and regenerative capabilities of articular cartilage are limited, its repair remains one of the most challenging issues of musculoskeletal medicine. Clinical treatments intended to promote the success and complete repair of partial- and fullthickness articular cartilage defects are still unpredictable. However, one of the most exciting theories is that treatment of damaged articular cartilage can be realized with cartilage tissue engineering. This notion has prompted tissue engineering research involving cells, stimulating factors and scaffolds, either alone or in combination. With these perspectives, this review aims to present a summary of cartilage tissue engineering including development, recent progress, and major steps taken toward the regeneration of functional cartilage tissue. In addition, we discussed the role of stimulating factors, including growth factors, gene therapies, biophysical stimuli, and bioreactors, as well as scaffolds, including natural, synthetic, and nanostructured scaffolds, in cartilage tissue regeneration. Special emphasis was placed on cell source, including chondrocytes, fibroblasts, and stem cells, as an important component of cartilage tissue engineering techniques. In conclusion, continued development of cartilage tissue engineering will support future applications for patients suffering from diseased cartilage tissue problems and osteoarthritis.

Background: The articular cartilage is unique in that it contains only a single type of cell and shows poor ability for spontaneous healing. Currently, approaches for treating cartilage defects include surgical and nonsurgical approaches, as well as cartilage tissue engineering. For standard cartilage tissue engineering, three elements are required, i.e., a scaffold, growth factors, and seed cells. With advancements in stem cell research, the main sources of cells for cartilage tissue engineering are embryonic and mesenchymal stem cells, which have been shown to be promising alternatives in recent years. Objective: In this review, we focus on the applications of various stem cells in cartilage tissue engineering. Results: Under certain conditions, several types of stem cells, including embryonic stem cells, mesenchymal stem cells, induced pluripotent stem cells, and cartilage progenitor cells, showed potential for applications in chondrogenic differentiation. Conclusion: Stem cells can be developed as important cell sources for cartilage tissue engineering if appropriate microenvironments and bioactive factors are supplied. However, further studies are needed to determine the ideal cell type for cartilage repair, particularly using in vivo and clinical studies.

Background: Cellular differentiation occurs in a complicated microenvironment containing multiple components including soluble factors and physical cues. In addition to biochemical composition, physical cues are also crucial in determining cellular behaviors. Objective: To better understand the interaction between physical signals and cells, we discuss the effects of physical cues on cellular behaviors, especially chondrogenic differentiation in vitro. Furthermore, the mechanisms by which these physical signals are transmitted from the extracellular matrix into the cell are also considered. Results: Physical cues can dramatically regulate specific cellular functions in cartilage tissue engineering. Integrin and FAs act as mechano-sensors to transmit physical cues from the ECM into cytoskeleton- signaling network. Meanwhile, the RhoA/ROCK signaling pathway and YAP/TAZ play indispensable roles in cell and ECM linkages. Conclusion: The investigation of physical cues clarifies cellular behaviors. This information can be applied to tissue engineering scaffold and biological material production in the future.

The management of chondral defects has been a challenge for a long time because of the poor self-healing capacity of articular cartilage. Many approaches ranging from symptomatic treatment to structural cartilage regeneration are not that successful with very limited satisfactory results. Chondral defects caused by tumor, trauma, infection, congenital malformations are very common in clinical trials. It seriously affects the patient's physical function and quality of life. The appearance of cartilage tissue engineering has brought good news for cartilage defect repair. Through this review, we are aimed at reviewing the progress of the types and preparation techniques of scaffold materials in cartilage tissue engineering.

Background: Cartilage injury has always been puzzled for clinicians. The treatments used clinically for cartilage injury usually bring about fibrocartilage. The emergence of tissue engineering lights up the hope of cartilage repair. Objective: This review will sum up the existing learnings about electrospun fibers, revolving about the electrospinning materials, micromorphology, improvements and electrospun technologies newly developed in cartilage repair and regeneration. Results: Electrospun fibers as scaffolds for cartilage regeneration have been one of researching hotspots for years. The studies about new electrospun materials and new electrospinning technologies greatly promoted the development of this field. Conclusion: Electrospun fibers have showed great potential in cartilage regeneration. But there is still a long way to go before clinical application. The material embellishment and structure imitation should be highlighted in future.

Cartilage, as a nanostructured tissue, because of its awfully poor capacity for inherent regeneration and complete hierarchical structure, is severely difficult to regenerate after damages. Tissue engineering methods have provided a great contribution for cartilage repair. Nanomaterials have special superiority in regulating stem cell behaviors due to their special mechanical and biological properties and biomimetic characteristics. Therefore, they have been given great attention in tissue regeneration. Nanomaterials are divided into organic and inorganic nanomaterials. They provide the microenvironment to support differentiation of stem cells. Nanomaterials inducing stem cells to differentiate into chondrocyte phenotypes would be a benefit for cartilage tissue regeneration, then promoting the development of cartilage tissue engineering. In this review, we summarized the important roles of nanomaterials in chondrogenic differentiation of stem cells.

Nerve injury is a large problem that produces much pain in patients. Injury to the nervous system causes serious consequences and affects a person's quality of life. The development of tissue engineering has created a brighter future for nerve regeneration, and research has not stopped since the discovery of stem cells. Stem cells are a type of pluripotent cell that exhibits the capacity of selfdifferentiation and proliferation. Many studies have demonstrated the ability of stem cells to differentiate into other types of cells, including neurons, after induction with trophic factors in vivo and in vitro. Scientists have isolated a variety of stem cells from different organs and tissues in the human body and demonstrated that these cells were efficacious in regenerative medicine. The use of these cells provides a non-surgical method for the treatment of neurological diseases, such as nerve defects. However, many problems must be resolved before using these cells in the clinical field. The microenvironment and delivery methods of cells also affect the regeneration process. The present article comprehensively summarizes the progress of stem cells in the field of nerve regeneration in the recent decades.