scholarly journals An Approach to In Vitro Manufacturing of Hypertrophic Cartilage Matrix for Bone Repair

2017 ◽  
Vol 4 (4) ◽  
pp. 35 ◽  
Author(s):  
Bach Quang Le ◽  
Clemens Van Blitterswijk ◽  
Jan De Boer
Polymers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 2302
Author(s):  
Qingwen Yu ◽  
Zhiyuan Meng ◽  
Yichao Liu ◽  
Zehao Li ◽  
Xing Sun ◽  
...  

After an osteosarcoma excision, recurrence and bone defects are significant challenges for clinicians. In this study, the curcumin (Cur) loaded chitosan (CS) nanoparticles (CCNP) encapsulated silk fibroin (SF)/hyaluronic acid esterified by methacrylate (HAMA) (CCNPs-SF/HAMA) hydrogel for the osteosarcoma therapy and bone regeneration was developed by photocuring and ethanol treatment. The micro or nanofibers networks were observed in the CCNPs-SF/HAMA hydrogel. The FTIR results demonstrated that alcohol vapor treatment caused an increase in β-sheets of SF, resulting in the high compression stress and Young’s modulus of CCNPs-SF/HAMA hydrogel. According to the water uptake analysis, SF caused a slight decrease in water uptake of CCNPs-SF/HAMA hydrogel while CCNPs could enhance the water uptake of it. The swelling kinetic results showed that both the CCNPs and the SF increased the swelling ratio of CCNPs-SF/HAMA hydrogel. The accumulative release profile of CCNPs-SF/HAMA hydrogel showed that the release of Cur from CCNPs-SF/HAMA hydrogel was accelerated when pH value was decreased from 7.4 to 5.5. Besides, compared with CCNPs, the CCNPs-SF/HAMA hydrogel had a more sustainable drug release, which was beneficial for the long-term treatment of osteosarcoma. In vitro assay results indicated that CCNPs-SF/HAMA hydrogel with equivalent Cur concentration of 150 μg/mL possessed both the effect of anti-cancer and promoting the proliferation of osteoblasts. These results suggest that CCNPs-SF/HAMA hydrogel with superior physical properties and the bifunctional osteosarcoma therapy and bone repair may be an excellent candidate for local cancer therapy and bone regeneration.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Sebastian Kühn ◽  
Joanna Freyse ◽  
Passant Atallah ◽  
Jörg Rademann ◽  
Uwe Freudenberg ◽  
...  

Abstract The delivery of chemotactic signaling molecules via customized biomaterials can effectively guide the migration of cells to improve the regeneration of damaged or diseased tissues. Here, we present a novel biohybrid hydrogel system containing two different sulfated glycosaminoglycans (sGAG)/sGAG derivatives, namely either a mixture of short heparin polymers (Hep-Mal) or structurally defined nona-sulfated tetrahyaluronans (9s-HA4-SH), to precisely control the release of charged signaling molecules. The polymer networks are described in terms of their negative charge, i.e. the anionic sulfate groups on the saccharides, using two parameters, the integral density of negative charge and the local charge distribution (clustering) within the network. The modulation of both parameters was shown to govern the release characteristics of the chemotactic signaling molecule SDF-1 and allows for seamless transitions between burst and sustained release conditions as well as the precise control over the total amount of delivered protein. The obtained hydrogels with well-adjusted release profiles effectively promote MSC migration in vitro and emerge as promising candidates for new treatment modalities in the context of bone repair and wound healing.


Polymers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1797
Author(s):  
Manuel Toledano ◽  
Marta Vallecillo-Rivas ◽  
María T. Osorio ◽  
Esther Muñoz-Soto ◽  
Manuel Toledano-Osorio ◽  
...  

Barrier membranes are employed in guided bone regeneration (GBR) to facilitate bone in-growth. A bioactive and biomimetic Zn-doped membrane with the ability to participate in bone healing and regeneration is necessary. The aim of the present study is to state the effect of doping the membranes for GBR with zinc compounds in the improvement of bone regeneration. A literature search was conducted using electronic databases, such as PubMed, MEDLINE, DIMDI, Embase, Scopus and Web of Science. A narrative exploratory review was undertaken, focusing on the antibacterial effects, physicochemical and biological properties of Zn-loaded membranes. Bioactivity, bone formation and cytotoxicity were analyzed. Microstructure and mechanical properties of these membranes were also determined. Zn-doped membranes have inhibited in vivo and in vitro bacterial colonization. Zn-alloy and Zn-doped membranes attained good biocompatibility and were found to be non-toxic to cells. The Zn-doped matrices showed feasible mechanical properties, such as flexibility, strength, complex modulus and tan delta. Zn incorporation in polymeric membranes provided the highest regenerative efficiency for bone healing in experimental animals, potentiating osteogenesis, angiogenesis, biological activity and a balanced remodeling. Zn-loaded membranes doped with SiO2 nanoparticles have performed as bioactive modulators provoking an M2 macrophage increase and are a potential biomaterial for promoting bone repair. Zn-doped membranes have promoted pro-healing phenotypes.


2021 ◽  
Vol 11 (12) ◽  
pp. 2313-2320
Author(s):  
Jian Zhao ◽  
Wei Li ◽  
Xin Dong ◽  
Jiying Chen

Based on bioactive glasses (BG) of 58S, sol–gel method is used to prepare strontium oxide substituted bioactive glasses (SrO-BG) with different strontium content. SrO-BG and nano hydroxyapatite (HAp) composite materials were synthesized using precipitation method. The phase composition and morphologies of the prepared materials were examined by x-ray diffraction (XRD) and scanning electron microscopy (SEM) techniques. The dissolution and bio-mineralization of SrO-BG and SrO-BG/HAp composites in SBF are investigated by immersion method. The effects of secretion components of macrophages regulated by strontium doped SrO-BG/HAp composites on the osteogenic differentiation (OD) of bone marrow mesenchymal stem cells (BMSCs) are analyzed. The results demonstrate that the SrO-BG can inhibit the dissolution of BG. Different proportions of SrO-BG/HAp composites show good ability to induce HAp in SBF. The bio-mineralization ability of SrO-BG/HAp composites increases with the increase of SrO-BG content. The results of dissolution behavior and bio-mineralization of SrO-BG/HAp composite show that the dissolution rate of each ion can be controlled by adjusting the content of SrO-BG in the composite, and then the degradation rate can effectively be controlled. The results of in vitro experiments show that SrO-BG/HAp composites with 2%, 5% and 8% strontium content are more effective in promoting M2 polarization of macrophages than SrO-BG/HAp composites with 0% strontium content. Among them, 5% strontium doped SrO-BG/HAp has the strongest effect on M2 polarization of macrophages, and the secretion of macrophages regulated by 5% strontium doped SrO-BG/HAp composite is more conducive to bone repair.


2018 ◽  
Vol 33 (5) ◽  
pp. 543-557 ◽  
Author(s):  
Jianfei Cao ◽  
Yue Lu ◽  
Hechun Chen ◽  
Lifang Zhang ◽  
Chengdong Xiong

Poly(etheretherketone) exhibits good biocompatibility, excellent mechanical properties, and bone-like stiffness. However, the natural bio-inertness of pure poly(etheretherketone) hinders its applications in biomedical field, especially when direct bone-implant osteo-integration is desired. For developing an alternative biomaterial for load-bearing orthopedic application, combination of bioactive fillers with poly(etheretherketone) matrix is a feasible approach. In this study, a bioactive multi-walled carbon nanotubes/calcium polyphosphate/poly(etheretherketone) composite was prepared through a compounding and injection-molding process for the first time. Bioactive calcium polyphosphate was added to polymer matrix to enhance the bioactivity of the composite, and incorporation of multi-walled carbon nanotubes to composite was aimed to improve both the mechanical property and biocompatibility. Furthermore, the microstructures, surface hydrophilicity, and mechanical property of multi-walled carbon nanotubes/calcium polyphosphate/poly(etheretherketone) composite, as well as the cellular responses of MC3T3-E1 osteoblast cells to this material were investigated. The mechanical testing revealed that mechanical performance of the resulting ternary composite was significantly enhanced by adding the multi-walled carbon nanotubes and the mechanical values obtained were close to or higher than those of human cortical bone. More importantly, cell culture tests showed that initial cell adhesion, cell viability, and osteogenic differentiation of MC3T3-E1 cells were significantly promoted on the multi-walled carbon nanotubes/calcium polyphosphate/poly(etheretherketone) composite. Accordingly, the multi-walled carbon nanotubes/calcium polyphosphate/poly(etheretherketone) composite may be used as a promising bone repair material in dental and orthopedic applications.


Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1408
Author(s):  
Susumu Horikoshi ◽  
Mikihito Kajiya ◽  
Souta Motoike ◽  
Mai Yoshino ◽  
Shin Morimoto ◽  
...  

Three-dimensional clumps of mesenchymal stem cells (MSCs)/extracellular matrix (ECM) complexes (C-MSCs) can be transplanted into tissue defect site with no artificial scaffold. Importantly, most bone formation in the developing process or fracture healing proceeds via endochondral ossification. Accordingly, this present study investigated whether C-MSCs generated with chondro-inductive medium (CIM) can induce successful bone regeneration and assessed its healing process. Human bone marrow-derived MSCs were cultured with xeno-free/serum-free (XF) growth medium. To obtain C-MSCs, confluent cells that had formed on the cellular sheet were scratched using a micropipette tip and then torn off. The sheet was rolled to make a round clump of cells. The cell clumps, i.e., C-MSCs, were maintained in XF-CIM. C-MSCs generated with XF-CIM showed enlarged round cells, cartilage matrix, and hypertrophic chondrocytes genes elevation in vitro. Transplantation of C-MSCs generated with XF-CIM induced successful bone regeneration in the SCID mouse calvaria defect model. Immunofluorescence staining for human-specific vimentin demonstrated that donor human and host mouse cells cooperatively contributed the bone formation. Besides, the replacement of the cartilage matrix into bone was observed in the early period. These findings suggested that cartilaginous C-MSCs generated with XF-CIM can induce bone regeneration via endochondral ossification.


2018 ◽  
Vol 75 (10) ◽  
pp. 4515-4529 ◽  
Author(s):  
Adriana C. Motta ◽  
Vitor de Miranda Fedrizzi ◽  
Maria Lourdes Peri Barbo ◽  
Eliana A. R. Duek

2000 ◽  
Vol 113 (1) ◽  
pp. 59-69 ◽  
Author(s):  
M.F. Carlevaro ◽  
S. Cermelli ◽  
R. Cancedda ◽  
F. Descalzi Cancedda

Vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) induces endothelial cell migration and proliferation in culture and is strongly angiogenic in vivo. VEGF synthesis has been shown to occur in both normal and transformed cells. The receptors for the factor have been shown to be localized mainly in endothelial cells, however, the presence of VEGF synthesis and the VEGF receptor in cells other than endothelial cells has been demonstrated. Neoangiogenesis in cartilage growth plate plays a fundamental role in endochondral ossification. We have shown that, in an avian in vitro system for chondrocyte differentiation, VEGF was produced and localized in cell clusters totally resembling in vivo cartilage. The factor was synthesized by hypertrophic chondrocytes and was released into their conditioned medium, which is highly chemotactic for endothelial cells. Antibodies against VEGF inhibited endothelial cell migration induced by chondrocyte conditioned media. Similarly, endothelial cell migration was inhibited also by antibodies directed against the VEGF receptor 2/Flk1 (VEGFR2). In avian and mammalian embryo long bones, immediately before vascular invasion, VEGF was distinctly localized in growth plate hypertrophic chondrocytes. In contrast, VEGF was not observed in quiescent and proliferating chondrocytes earlier in development. VEGF receptor 2 colocalized with the factor both in hypertrophic cartilage in vivo and hypertrophic cartilage engineered in vitro, suggesting an autocrine loop in chondrocytes at the time of their maturation to hypertrophic cells and of cartilage erosion. Regardless of cell exposure to exogenous VEGF, VEGFR-2 phosphorylation was recognized in cultured hypertrophic chondrocytes, supporting the idea of an autocrine functional activation of signal transduction in this non-endothelial cell type as a consequence of the endogenous VEGF production. In summary we propose that VEGF is actively responsible for hypertrophic cartilage neovascularization through a paracrine release by chondrocytes, with invading endothelial cells as a target. Furthermore, VEGF receptor localization and signal transduction in chondrocytes strongly support the hypothesis of a VEGF autocrine activity also in morphogenesis and differentiation of a mesoderm derived cell.


2022 ◽  
pp. 088532822110492
Author(s):  
Zhenbao Zhang ◽  
Xirao Sun ◽  
Jingxin Yang ◽  
Chengyue Wang

Magnesium (Mg) alloy with good mechanical properties and biodegradability is considered as one of the ideal bone repair materials. However, the rapid corrosion of Mg-based metals can pose harm to the function of an implant in clinical applications. In this study, micro-arc oxidation coating was prepared on the surface of the Mg–Ca matrix, then the chitosan and mineralized collagen (nano-hydroxyapatite/collagen; nHAC) were immobilized on the surface of the MAO/Mg–Ca matrix to construct the CS-nHAC/Mg–Ca composites of different component proportions (the ratio of CS to nHAC is 2:1, 1:1, and 1:2, respectively). The corrosion resistance, osteogenic activity, and angiogenic ability were extensively investigated. The results indicated that the CS-nHAC reinforcement materials can improve the corrosion resistance of the Mg matrix significantly and promote the proliferation and adhesion of mouse embryo osteoblast precursor cells (MC3T3-E1) and human umbilical vein endothelial cells (HUVECs). In addition, the CS-nHAC/Mg–Ca composites can not only promote the alkaline phosphatase (ALP) activity and extracellular matrix mineralization of MC3T3-E1 cells but also enhance the migration motility and vascular endothelial growth factor (VEGF) expression of HUVECs. Meanwhile, the 2CS-1nHAC/Mg–Ca composite exhibited the optimum function characteristics compared with other samples. Therefore, considering the improvement of corrosion resistance and biocompatibility, the CS-nHAC/Mg–Ca composites are expected to be a promising orthopedic implant.


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