In this work the bone tissue remodelling analysis of the femur bone due to the insertion of a stem is analysed. The innovation of this numerical application lies on the use of an efficient advanced ...discretization meshless technique to obtain the variable fields required by the remodelling process.
The remodelling algorithm used in this work allows to update locally and gradually the bone tissue density of the model. Based on the minimization of the strain energy density (SED), the remodelling algorithm uses a phenomenological bone tissue mathematical law, which permits to correlate the bone apparent density with its own mechanical properties. Comparing with other numerical approaches, the advanced discretization meshless technique used in this work allows to obtain smoother and more accurate SED fields, leading to more reliable remodelling predictions.
The numerical remodelling results obtained for the femoral diaphysis after the insertion of the stem are in accordance with the clinical observation and with other numerical approaches results available in the literature.
Bionanocomposites formed by combining biodegradable polymers and nanosized osteoconductive inorganic solids have been regarded as promising biomimetic systems which possess much improved structural ...and functional properties for bone tissue regeneration. In this study three-dimensional nanocomposite scaffolds based on calcium phosphate (Ca-P)/poly(hydroxybutyrate–co-hydroxyvalerate) (PHBV) and carbonated hydroxyapatite (CHAp)/poly(
l-lactic acid) (PLLA) nanocomposite microspheres were successfully fabricated using selective laser sintering, which is a rapid prototyping technology. The sintered scaffolds had controlled material microstructure, totally interconnected porous structure and high porosity. The morphology and mechanical properties of Ca-P/PHBV and CHAp/PLLA nanocomposite scaffolds as well as PHBV and PLLA polymer scaffolds were studied. In vitro biological evaluation showed that SaOS-2 cells had high cell viability and normal morphology and phenotype after 3 and 7
days culture on all scaffolds. The incorporation of Ca-P nanoparticles significantly improved cell proliferation and alkaline phosphatase activity for Ca-P/PHBV scaffolds, whereas CHAp/PLLA nanocomposite scaffolds exhibited a similar level of cell response compared with PLLA polymer scaffolds. The nanocomposite scaffolds provide a biomimetic environment for osteoblastic cell attachment, proliferation and differentiation and have great potential for bone tissue engineering applications.
The rebuilding of the normal functioning of the damaged human body bone tissue is one of the main objectives of bone tissue engineering (BTE). Fabricated scaffolds are mostly treated as artificial ...supports and as materials for regeneration of neo bone tissues and must closely biomimetic the native extracellular matrix of bone. The materials used for developing scaffolds should be biodegradable, nontoxic, and biocompatible. For the resurrection of bone disorder, specifically natural and synthetic polymers such as chitosan, PCL, gelatin, PGA, PLA, PLGA, etc. meet the requirements for serving their functions as artificial bone substitute materials. Gelatin is one of the potential candidates which could be blended with other polymers or composites to improve its physicochemical, mechanical, and biological performances as a bone graft. Scaffolds are produced by several methods including electrospinning, self-assembly, freeze-drying, phase separation, fiber drawing, template synthesis, etc. Among them, freeze-drying and electrospinning are among the popular, simplest, versatile, and cost-effective techniques. The design and preparation of freeze-dried and electrospun scaffolds are of intense research over the last two decades. Freeze-dried and electrospun scaffolds offer a distinctive architecture at the micro to nano range with desired porosity and pore interconnectivity for selective movement of small biomolecules and play its role as an appropriate matrix very similar to the natural bone extracellular matrix. This review focuses on the properties and functionalization of gelatin-based polymer and its composite in the form of bone scaffolds fabricated primarily using lyophilization and electrospinning technique and their applications in BTE.
Critical-sized bone defects resulting from severe trauma and open fractures cannot spontaneously heal and require surgical intervention. Limitations of traditional bone grafting include immune ...rejection and demand-over-supply issues leading to the development of novel tissue-engineered scaffolds. Nuciferine (NF), a plant-derived alkaloid, has excellent therapeutic properties, but its osteogenic potential is yet to be reported. Furthermore, the bioavailability of NF is obstructed due to its hydrophobicity, requiring an efficient drug delivery system, such as chitosan (CS) hydrogel. We designed and fabricated polylactic acid (PLA) scaffolds via 3D printing and integrated them with NF-containing CS hydrogel to obtain the porous biocomposite scaffolds (PLA/CS-NF). The fabricated scaffolds were subjected to in vitro physicochemical characterization, cytotoxicity assays, and osteogenic evaluation studies. Scanning electron microscopic studies revealed uniform pore size distribution on PLA/CS-NF scaffolds. An in vitro drug release study showed a sustained and prolonged release of NF. The cyto-friendly nature of NF in PLA/CS-NF scaffolds towards mouse mesenchymal stem cells (mMSCs) was observed. Also, cellular and molecular level studies signified the osteogenic potential of NF in PLA/CS-NF scaffolds on mMSCs. These results indicate that the PLA/CS-NF scaffolds could promote new bone formation and have potential applications in bone tissue engineering.
Substantial tissue loss, such as in large bone defects, represents a clinical challenge for which regenerative therapies and tissue engineering strategies aim at offering treatment alternatives to ...conventional replacement approaches by metallic implants. 3D printing technologies provide endless opportunities to shape scaffold structures that could support endogenous regeneration. However, it remains unclear which of the numerous parameters at hand eventually enhance tissue regeneration. In the last decades, a significant effort has been made in the development of computer tools to optimize scaffold designs. Here, we aim at giving a more comprehensive overview summarizing current computer optimization framework technologies. We confront these with the most recent advances in scaffold mechano-biological optimization, discuss their limitations and provide suggestions for future development. We conclude that the field needs to move forward to not only optimize scaffolds to avoid implant failures but to improve their mechano-biological behaviour: providing an initial stimulus for fast tissue organisation and healing and accounting for remodelling, scaffold degradation and consecutive filling with host tissue. So far, modelling approaches fall short in including the various scales of tissue dynamics. With this review, we wish to stimulate a move towards multi-dynamic mechano-biological optimization of 3D-printed scaffolds.
Large bone defects represent a clinical challenge for which tissue engineering strategies aim at offering alternatives to conventional treatment strategies. 3D printing technologies provide endless opportunities to shape scaffold structures that could support endogenous regeneration. However, it remains unclear which of the numerous parameters at hand eventually enhance tissue regeneration. In the last decades, a significant effort has been made in the development of computer tools to optimize scaffold designs. This review summarizes current computer optimization frameworks and most recent advances in mechano-biological optimization of bone scaffolds to better stimulate bone regeneration. We wish to stimulate a move towards multi-dynamic mechano-biological optimization of 3D-printed scaffolds.
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To analyze the extant literature describing the application of gene therapy to spinal fusion.
A systematic review of the English-language literature was performed. The search query was designed to ...include all published studies examining gene therapy approaches to promote spinal fusion. Approaches were classified as ex vivo (delivery of genetically modified cells) or in vivo (delivery of growth factors via vectors). The primary endpoint was fusion rate. Random effects meta-analyses were performed to calculate the overall odds ratio (OR) of fusion using a gene therapy approach and overall fusion rate. Subgroup analyses of fusion rate were also performed for each gene therapy approach.
Of 1179 results, 35 articles met criteria for inclusion (all preclinical), of which 26 utilized ex vivo approaches and 9 utilized in vivo approaches. Twenty-seven articles (431 animals) were included in the meta-analysis. Gene therapy use was associated with significantly higher fusion rates (OR 77; 95% confidence interval {CI}: 31, 192; P < 0.001); ex vivo strategies had a greater effect (OR 136) relative to in vivo strategies (OR 18) (P = 0.017). The overall fusion rate using a gene therapy approach was 80% (95% CI: 62%, 93%; P < 0.001); overall fusion rates were significantly higher in subjects treated with ex vivo compared to in vivo strategies (90% vs. 42%; P = 0.011). For both ex vivo and in vivo approaches, the effect of gene therapy on fusion was independent of animal model.
Gene therapy may augment spinal fusion; however, future investigation in clinical populations is necessary.
Bioprinting can be defined as 3D patterning of living cells and other biologics by filling and assembling them using a computer-aided layer-by-layer deposition approach to fabricate living tissue and ...organ analogs for tissue engineering. The presence of cells within the ink to use a 'bio-ink' presents the potential to print 3D structures that can be implanted or printed into damaged/diseased bone tissue to promote highly controlled cell-based regeneration and remineralization of bone. In this study, it was shown for the first time that chitosan solution and its composite with nanostructured bone-like hydroxyapatite (HA) can be mixed with cells and printed successfully. MC3T3-E1 pre-osteoblast cell laden chitosan and chitosan-HA hydrogels, which were printed with the use of an extruder-based bioprinter, were characterized by comparing these hydrogels to alginate and alginate-HA hydrogels. Rheological analysis showed that all groups had viscoelastic properties. It was also shown that under simulated physiological conditions, chitosan and chitosan-HA hydrogels were stable. Also, the viscosity values of the bio-solutions were in an applicable range to be used in 3D bio-printers. Cell viability and proliferation analyses documented that after printing with bio-solutions, cells continued to be viable in all groups. It was observed that cells printed within chitosan-HA composite hydrogel had peak expression levels for early and late stages osteogenic markers. It was concluded that cells within chitosan and chitosan-HA hydrogels had mineralized and differentiated osteogenically after 21 days of culture. It was also discovered that chitosan is superior to alginate, which is the most widely used solution preferred in bioprinting systems, in terms of cell proliferation and differentiation. Thus, applicability and printability of chitosan as a bio-printing solution were clearly demonstrated. Furthermore, it was proven that the presence of bone-like nanostructured HA in alginate and chitosan hydrogels improved cell viability, proliferation and osteogenic differentiation.
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