Utilizing osteocyte derived factors to enhance cell viability and osteogenic matrix deposition within IPN hydrogels

Many bone defects arising due to traumatic injury, disease, or surgery are unable to regenerate, requiring intervention. More than four million graft procedures are performed each year to treat these defects making bone the second most commonly transplanted tissue worldwide. However, these types of graft suffer from a limited supply, a second surgical site, donor site morbidity, and pain. Due to the unmet clinical need for new materials to promote skeletal repair, this study aimed to produce novel biomimetic materials to enhance stem/stromal cell osteogenesis and bone repair by recapitulating aspects of the biophysical and biochemical cues found within the bone microenvironment. Utilizing a collagen type I-alginate interpenetrating polymer network we fabricated a material which mirrors the mechanical and structural properties of unmineralized bone, consisting of a porous fibrous matrix with a young's modulus of 64 kPa, both of which have been shown to enhance mesenchymal stromal/stem cell (MSC) osteogenesis. Moreover, by combining this material with biochemical paracrine factors released by statically cultured and mechanically stimulated osteocytes, we further mirrored the biochemical environment of the bone niche, enhancing stromal/stem cell viability, differentiation, and matrix deposition. Therefore, this biomimetic material represents a novel approach to promote skeletal repair

Bioactive SrO-SiO2 glass with well-ordered mesopores: Characterization, physiochemistry and biological properties

For a biomaterial to be considered suitable for bone repair it should ideally be both bioactive and have a capacity for controllable drug delivery; as such, mesoporous SiO2 glass has been proposed as a new class of bone regeneration material by virtue of its high drug-loading ability and generally good biocompatibility. It does, however, have less than optimum bioactivity and controllable drug delivery properties. In this study, we incorporated strontium (Sr) into mesoporous SiO2 in an effort to develop a bioactive mesoporous SrO–SiO2 (Sr–Si) glass with the capacity to deliver Sr2+ ions, as well as a drug, at a controlled rate, thereby producing a material better suited for bone repair. The effects of Sr2+ on the structure, physiochemistry, drug delivery and biological properties of mesoporous Sr–Si glass were investigated. The prepared mesoporous Sr–Si glass was found to have an excellent release profile of bioactive Sr2+ ions and dexamethasone, and the incorporation of Sr2+ improved structural properties, such as mesopore size, pore volume and specific surface area, as well as rate of dissolution and protein adsorption. The mesoporous Sr–Si glass had no cytotoxic effects and its release of Sr2+ and SiO44− ions enhanced alkaline phosphatase activity – a marker of osteogenic cell differentiation – in human bone mesenchymal stem cells. Mesoporous Sr–Si glasses can be prepared to porous scaffolds which show a more sustained drug release. This study suggests that incorporating Sr2+ into mesoporous SiO2 glass produces a material with a more optimal drug delivery profile coupled with improved bioactivity, making it an excellent material for bone repair applications. Keywords: Mesoporous Sr–Si glass; Drug delivery; Bioactivity; Bone repair; Scaffold

Enhanced Osteogenesis of Adipose-Derived Stem Cells by Regulating Bone Morphogenetic Protein Signaling Antagonists and Agonists.

UnlabelledAlthough adipose-derived stem cells (ASCs) are an attractive cell source for bone tissue engineering, direct use of ASCs alone has had limited success in the treatment of large bone defects. Although bone morphogenetic proteins (BMPs) are believed to be the most potent osteoinductive factors to promote osteogenic differentiation of ASCs, their clinical applications require supraphysiological dosage, leading to high medical burden and adverse side effects. In the present study, we demonstrated an alternative approach that can effectively complement the BMP activity to maximize the osteogenesis of ASCs without exogenous application of BMPs by regulating levels of antagonists and agonists to BMP signaling. Treatment of ASCs with the amiloride derivative phenamil, a positive regulator of BMP signaling, combined with gene manipulation to suppress the BMP antagonist noggin, significantly enhanced osteogenic differentiation of ASCs through increased BMP-Smad signaling in vitro. Furthermore, the combination approach of noggin suppression and phenamil stimulation enhanced the BMP signaling and bone repair in a mouse calvarial defect model by adding noggin knockdown ASCs to apatite-coated poly(lactic-coglycolic acid) scaffolds loaded with phenamil. These results suggest novel complementary osteoinductive strategies that could maximize activity of the BMP pathway in ASC bone repair while reducing potential adverse effects of current BMP-based therapeutics.SignificanceAlthough stem cell-based tissue engineering strategy offers a promising alternative to repair damaged bone, direct use of stem cells alone is not adequate for challenging healing environments such as in large bone defects. This study demonstrates a novel strategy to maximize bone formation pathways in osteogenic differentiation of mesenchymal stem cells and functional bone formation by combining gene manipulation with a small molecule activator toward osteogenesis. The findings indicate promising stem cell-based therapy for treating bone defects that can effectively complement or replace current osteoinductive therapeutics

Use of natural resins in repairing damaged timber beams – An experimental investigation

Different techniques including the application of steel elements, composite materials and polymeric resins have been used in the past to repair damaged timber beams. However, there is a growing need to replace these materials with those with minimal environmental impact. In addition, stringent requirements of conservation authorities on the compatibility between repair and parent materials have also necessitated search for innovative repair materials for timber beams. Therefore, an increasing shift of focus towards the use of materials derived from natural sources in repairing and reinforcing timber structures is currently experienced. This paper presents the results of an exploratory study on the use of natural resins (rosin and bone glue) in repairing oak timber beams. 15 oak timber beams with cross section dimensions of 67 x 67 mm and 1100 mm in length were tested in four-point bending to failure. Undamaged, damaged (unrepaired) and damaged but repaired timber beams (with rosin and bone glue) were tested. The effectiveness of the repair material and technique was analysed based on the bending capacity and mid span deflection at failure. The initial results show negligible effectiveness of rosin in repairing timber beams. In fact, about 16% reduction (average) in load carrying capacity with a corresponding 5% decrease (average) in maximum displacement was recorded. Relatively higher level of effectiveness was recorded with the use of bone glue (about 10 % average increase in load carrying capacity). However, over 30% corresponding average increase in the maximum displacement was also recorded. Further work investigating different repair techniques and other natural resins is presently underway

Bone repair in adult rats with osteoporosis

The bone repair is a key point in modern medicine. The process of bone repair involves not only the injured bone tissue but also all surrounding tissues and leads changes in whole body. Also numerous pathology can affect the bone repair process and even leads a disregeneration. There are a lot of articles about the bone repair pathology in case of diabetis, other endocrine pathology, water and salts disbalance and so on. And one of principal disease that can affect bone healing process is a osteoporosis that is a pathology of calcium and phosphorus metabolism and leads the lost of bone density and decreasing its mechanical properties. When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/3579

CaSiO3 microstructure modulating the in vitro and in vivo bioactivity of poly(lactide-co-glycolide) microspheres

Poly (lactide-co-glycolide) (PLGA) microspheres have been used for regenerative medicine due to their ability for drug delivery and generally good biocompatibility, but they lack adequate bioactivity for bone repair application. CaSiO3 (CS) has been proposed as a new class of material suitable for bone tissue repair due to its excellent bioactivity. In this study, we set out to incorporate CS into PLGA microspheres to investigate how the phase structure (amorphous and crystal) of CS influences the in vitro and in vivo bioactivity of the composite microspheres, with a view to the application for bone regeneration. X-ray diffraction (XRD), N2 adsorption-desorption analysis and scanning electron microscopy (SEM) were used to analyze the phase structure, surface area/pore volume, and microstructure of amorphous CS (aCS) and crystal CS (cCS), as well as their composite microspheres. The in vitro bioactivity of aCS and cCS – PLGA microspheres was evaluated by investigating their apatite-mineralization ability in simulated body fluids (SBF) and the viability of human bone mesenchymal stem cells (BMSCs). The in vivo bioactivity was investigated by measuring their de novo bone-formation ability. The results showed that the incorporation of both aCS and cCS enhanced the in vitro and in vivo bioactivity of PLGA microspheres. cCS/PLGA microspheres improved better in vitro BMSC viability and de novo bone-formation ability in vivo, compared to aCS/PLGA microspheres. Our study indicates that controlling the phase structure of CS is a promising method to modulate the bioactivity of polymer microsphere system for potential bone tissue regeneration

A radiographic survey of eggshell powder effect on tibial bone defect repair tested in dog

Abstract. Objective: Nowadays, skeletal system injuries are of major importance. In addition, it is recommended to use materials for hard tissue repair in open or closed fractures. It is important to use complex minerals with a beneficial effect on hard tissue repair, stimulating cell growth in the bone. Materials that could help avoid bone fracture inflammatory reaction and speed up bone fracture repair are of utmost importance in the treatment of bone fractures.Material and Method: Similar to minerals, the inner eggshell membrane consists of carbohydrates, lipids, proteins with high pH, high calcium absorptive capacity and with faster bone fracture repair ability. In the present radiographic survey, eggshell-derived bone graft substitutes were used for bone defect repair in 8 dog tibia, measuring bone density on the day of implant placement and 30 and 60 days after placement. Results: In fact, the result of this study shows the difference in bone growth and misshapen bones between treatment and control sites. Conclusion: Cell growth was adequate in treatment sites and misshapen bones were less frequent here than in control sites

Systemic DKK1 neutralization enhances human adipose-derived stem cell mediated bone repair

: Progenitor cells from adipose tissue are able to induce bone repair; however, inconsistent or unreliable efficacy has been reported across preclinical and clinical studies. Soluble inhibitory factors, such as the secreted Wnt signaling antagonists Dickkopf-1 (DKK1), are expressed to variable degrees in human adipose-derived stem cells (ASCs), and may represent a targetable "molecular brake" on ASC mediated bone repair. Here, anti-DKK1 neutralizing antibodies were observed to increase the osteogenic differentiation of human ASCs in vitro, accompanied by increased canonical Wnt signaling. Human ASCs were next engrafted into a femoral segmental bone defect in NOD-Scid mice, with animals subsequently treated with systemic anti-DKK1 or isotype control during the repair process. Human ASCs alone induced significant but modest bone repair. However, systemic anti-DKK1 induced an increase in human ASC engraftment and survival, an increase in vascular ingrowth, and ultimately improved bone repair outcomes. In summary, anti-DKK1 can be used as a method to augment cell-mediated bone regeneration, and could be particularly valuable in the contexts of impaired bone healing such as osteoporotic bone repair

Cell Therapy and Tissue Engineering in Bone Defect Reconstruction; A Review

Background: Extensive research on bone tissue engineering as a novel therapeutic approach to design and fabricate suitable scaffolds is in progress to overcome the limitations of conventional bone repair techniques. In recent years, tissue engineering and remedial medicine have come up with the strategy of designing, fabricating, and optimizing synthetic and natural scaffolds containing cells and growth factors to facilitate the direct and indirect mechanisms of bone tissue repair in the body. Based on many studies, cellular source, cell medium condition, and biological scaffolds are critical factors in bone defect repair in the field of tissue engineering.Aim: In this review, we focus on the combination of mesenchymal cells derived from the human adipose tissue, stem cell-to-bone differentiation medium, and biocompatible polyvinyl alcohol-graphene oxide scaffolds in bone lesion repair to gain a better understanding of each factor. This would, in turn, help us design and develop optimal therapeutic approaches for bone repair and regeneration. Conclusion: The combination of mesenchymal cells and biocompatible scaffolds proved promising in the process of bone lesion repair