Figure - available from: Journal of Biomedical Materials Research Part B Applied Biomaterials
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MTT assay results expressed as % basal, taking as basal the cell viability under control conditions at 24 hr. RAW 264.7 macrophages cultured for 24 and 48 hr with chitosan, CHT; poly(l‐lactic acid), PLLA; and CHT + PLLA microspheres. Data represent the mean ± SEM
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The objective of this study was to test a regenerative medicine strategy for the regeneration of articular cartilage. This approach combines microfracture of the subchondral bone with the implant at the site of the cartilage defect of a supporting biomaterial in the form of microspheres aimed at creating an adequate biomechanical environment for th...
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... On the other hand, it allows mesenchymal cells to easily migrate from the subchondral bone if the implantation of the support material is combined with an injury to the subchondral bone with techniques such as microfracture. This strategy allowed the formation of a tissue with all the characteristics of hyaline cartilage in a rabbit knee model [23]. ...
The aim of this work is to study the effect of platelet factors on the differentiation of mesenchymal stem cells (MSCs) to hyaline cartilage chondrocytes in a three-dimensional environment. MSCs were cultured in a microgel environment with a chondrogenic medium. The microgel consisted of microspheres that combine gelatin and platelet-rich plasma (PRP). The gelatin/PRP microdroplets were produced by emulsion. The gelatin containing the microdroplets was enzymatically gelled, retaining PRP and, just before seeding the cells, platelets were activated by adding calcium chloride so that platelet growth factors were released into the culture media but not before. Platelet activation was analyzed before activation to rule out the possibility that the gelatin cross-linking process itself activated the platelets. The gene expression of characteristic chondrogenic markers and miRNA expression were analyzed in cells cultured in a differentiation medium and significant differences were found between gelation/PRP microgels and those containing only pure gelatin. In summary, the gelatin microspheres effectively encapsulated platelets that secreted and released factors that significantly contributed to cellular chondrogenic differentiation. At the same time, the microgel constituted a 3D medium that provided the cells with adherent surfaces and the possibility of three-dimensional cell–cell contact.
... The cells are seeded into the space between the microspheres, whose surface can be functionalised to provide cell adhesion sequences [14][15][16], while the microspheres themselves can support the release of growth factors during culture [17,18]. The same strategy can be used for in vivo tissue regeneration [19]. ...
Alginate hydrogels can be used to develop a three-dimensional environment in which various cell types can be grown. Cross-linking the alginate chains using reversible ionic bonds opens up great possibilities for the encapsulation and subsequent release of cells or drugs. However, alginate also has a drawback in that its structure is not very stable in a culture medium with cellular activity. This work explored the stability of alginate microspheres functionalised by grafting specific biomolecules onto their surface to form microgels in which biomimetic microspheres surrounded the cells in the culture, reproducing the natural microenvironment. A study was made of the stability of the microgel in different typical culture media and the formation of polyelectrolyte multilayers containing polylysine and heparin. Multiple myeloma cell proliferation in the culture was tested in a bioreactor under gentle agitation.
... Recently, bioactive drugs loaded CS microspheres (CMs) advanced their osteogenic potential in tissue regeneration and controlled drug delivery applications [15]. Additionally, CMs has been employed to synthesize CMs/polymer scaffold for the treatment of bone defects [16]. Li et al. reported that adiponectin-loaded CMs embedded in PLGA/β-TCP scaffold increased bone formation and mineralization [17]. ...
The development of functional materials for osteoporosis is ultimately required for bone remodeling. However, grafts were accompanied by increasing pro-inflammatory cytokines that impaired bone formation. In this work, nano-hydroxyapatite (n-HA)/resveratrol (Res)/chitosan (CS) composite microspheres were designed to create a beneficial microenvironment and help improve the osteogenesis by local sustained release of Res. Study of in vitro release confirmed the feasibility of n-HA/Res/CS microspheres for controlled Res release. Notably, microspheres had anti-inflammatory activity evidenced by the decreased expression of pro-inflammatory cytokines TNF-α, IL-1β and iNOS in RAW264.7 cells in a dose dependent manner. Further, enhanced adhesion and proliferation of BMSCs seeded onto microspheres demonstrated that composite microspheres were conducive to cell growth. The ability to enhance osteo-differentiation was supported by up-regulation of Runx2, ALP, Col-1 and OCN, and substantial mineralization in osteogenic medium. When implanted into bone defects in the osteoporotic rat femoral condyles, enhanced entochondrostosis and bone regeneration suggested that the n-HA/Res/CS composite microspheres were more favorable for impaired fracture healing. The results indicated that optimized n-HA/Res/CS composite microspheres could serve as promising multifunctional fillers for osteoporotic bone defect/fracture treatment.
... In recent years, many studies have demonstrated the effects of COX-2 inhibitors on bone, however, the effects of COX-2 inhibitors (such as Etoricoxib) on subchondral bone in OA are still unclear, especially the role of COX-2 inhibitors on its microstructure [11,[22][23][24]. The microscopic biomechanical environment of knee subchondral bone is very important for the repair/degeneration of subchondral bone cells [25]. ...
Etoricoxib, a selective Cyclooxygenase-2 (COX-2) inhibitor, is commonly used in osteoarthritis (OA) for pain relief, however, little is known about the effects on subchondral bone. In the current study, OA was induced via destabilization of the medial meniscus (DMM) in C57BL/6 mice. Two days after surgery, mice were treated with different concentrations of Etoricoxib. Four weeks after treatment, micro computed tomography (Micro-CT) analysis, histological analysis, atomic force microscopy (AFM) analysis, and scanning electron microscopy (SEM) were performed to evaluate OA progression. We demonstrated that Etoricoxib inhibited osteophyte formation in the subchondral bone. However, it also reduced the bone volume fraction (BV/TV), lowered trabecular thickness (Tb.Th), and more microfractures and pores were observed in the subchondral bone. Moreover, Etoricoxib reduced the elastic modulus of subchondral bone. Exposure to Etoricoxib further increased the empty/total osteocyte ratio of the subchondral bone. Etoricoxib did not show significant improvement in articular cartilage destruction and synovial inflammation in early OA. Together, our observations suggested that although Etoricoxib can relieve OA-induced pain and inhibit osteophyte formation in the subchondral bone, it can also change the microstructures and biomechanical properties of subchondral bone, promote subchondral bone loss, and reduce subchondral bone quality in early OA mice.
Articular cartilage regeneration is one of the challenges faced by orthopedic surgeons. Microcarrier applications have made great advances in cartilage tissue engineering in recent years and enable cost-effective cell expansion, thus providing permissive microenvironments for cells. In addition, microcarriers can be loaded with proteins, factors, and drugs for cartilage regeneration. Some microcarriers also have the advantages of injectability and targeted delivery. The application of microcarriers with these characteristics can overcome the limitations of traditional methods and provide additional advantages. In terms of the transformation potential, microcarriers have not only many advantages, such as providing sufficient and beneficial cells, factors, drugs, and microenvironments for cartilage regeneration, but also many application characteristics; for example, they can be injected to reduce invasiveness, transplanted after microtissue formation to increase efficiency, or combined with other stents to improve mechanical properties. Therefore, this technology has enormous potential for clinical transformation. In this review, we focus on recent advances in microcarriers for cartilage regeneration. We compare the characteristics of microcarriers with other methods for repairing cartilage defects, provide an overview of the advantages of microcarriers, discuss the potential of microcarrier systems, and present an outlook for future development.
Translational potential of this article
We reviewed the advantages and recent advances of microcarriers for cartilage regeneration. This review could give many scholars a better understanding of microcarriers, which can provide doctors with potential methods for treating patients with cartilage injure.
Regenerative medicine is an interdisciplinary field aiming to restore the function of diseased or damaged tissues by combining cells, bioactive molecules and biomaterial scaffolds. Polysaccharides have gained growing interest over the last years as promising biomaterials for scaffolds fabrication due to their natural origin, resemblance to the extracellular matrix, biocompatibility and non-toxicity. This Chapter presents the range of polysaccharides used in regenerative medicine applications. In the first part of the Chapter we will focus on the physicochemical and biological properties of the most common polysaccharides employed in tissue engineering applications. We will also present the functionalization/modification approaches employed to obtain polysaccharide derivatives with properties that render them particularly attractive for use in scaffold fabrication for tissue regeneration. In the second part, of the Chapter we will discuss the applications of polysaccharide-based materials in the regeneration of bone, cartilage, cardiovascular, neural and skin tissues, as well as in wound healing.
Recent studies have shown the relevance of growing mesenchymal stem cells (MSCs) in three-dimensional environments with respect to the monolayer cell culture on an adherent substrate. In this sense, macroporous scaffolds and hydrogels have been used as three-dimensional (3D) supports. In this work, we explored the culture of MSCs in a 3D environment created by microspheres, prepared with a fumarate-vinyl acetate copolymer and chitosan. In this system, the environment that the cells feel has similarities to that found by the cells encapsulated in a hydrogel, but the cells have the ability to reorganize their environment since the microspheres are mobile. We evaluated their biocompatibility in vitro using RAW 264.7 macrophages and bone marrow mesenchymal stem cells (BMSCs). The results with RAW 264.7 cells showed good cell viability, without evident signs of cytotoxicity. BMSCs not only proliferate, but also rearrange to grow in clusters, thus highlighting the advantages of microspheres as 3D environments.
