Focal adhesions are polyproteins linked to extracellular matrix and cytoskeleton,which play an important role in the process of transforming force signals into intracellular chemical signals and subsequently triggerin...Focal adhesions are polyproteins linked to extracellular matrix and cytoskeleton,which play an important role in the process of transforming force signals into intracellular chemical signals and subsequently triggering related physiological or pathological reactions.The cytoskeleton is a network of protein fibers in the cytoplasm,which is composed of microfilaments,microtubules,intermediate filaments,and cross-linked proteins.It is a very important structure for cells to maintain their basic morphology.This review summarizes the process of fluid shear stress transduction mediated by focal adhesion and the key role of the cytoskeleton in this process,which focuses on the focal adhesion and cytoskeleton systems.The important proteins involved in signal transduction in focal adhesion are introduced emphatically.The relationship between focal adhesion and mechanical transduction pathways are discussed.In this review,we discuss the relationship between fluid shear stress and associated diseases such as atherosclerosis,as well as its role in clinical research and drug development.展开更多
Next-generation synthetic bone graft therapies will most likely be composed of resorbable polymers in combination with bioactive components.In this article,we continue our exploration of E1001(1k),a tyrosine-derived p...Next-generation synthetic bone graft therapies will most likely be composed of resorbable polymers in combination with bioactive components.In this article,we continue our exploration of E1001(1k),a tyrosine-derived polycarbonate,as an orthopedic implant material.Specifically,we use E1001(1k),which is degradable,nontoxic,and osteoconductive,to fabricate porous bone regeneration scaffolds that were enhanced by two different types of calcium phosphate(CP)coatings:in one case,pure dicalcium phosphate dihydrate was precipitated on the scaffold surface and throughout its porous structure(E1001(1k)+CP).In the other case,bone matrix minerals(BMM)such as zinc,manganese and fluoride were co-precipitated within the dicalcium phosphate dihydrate coating(E1001(1k)+BMM).These scaffold compositions were compared against each other and against ChronOS(Synthes USA,West Chester,PA,USA),a clinically used bone graft substitute(BGS),which served as the positive control in our experimental design.This BGS is composed of poly(lactide co-e-caprolactone)and beta-tricalcium phosphate.We used the established rabbit calvaria critical-sized defect model to determine bone regeneration within the defect for each of the three scaffold compositions.New bone formation was determined after 2,4,6,8 and 12 weeks by micro-computerized tomography(mCT)and histology.The experimental tyrosine-derived polycarbonate,enhanced with dicalcium phosphate dihydrate,E1001(1k)+CP,supported significant bone formation within the defects and was superior to the same scaffold containing a mix of BMM,E1001(1k)+BMM.The comparison with the commercially available BGS was complicated by the large variability in bone formation observed for the laboratory preparations of E1001(1k)scaffolds.At all time points,there was a trend for E1001(1k)+CP to be superior to the commercial BGS.However,only at the 6-week time point did this trend reach statistical significance.Detailed analysis of the μCT data suggested an increase in bone formation from 2 through 12 weeks in implant sites treated with E1001(1k)+CP.At 2 and 4 weeks post-implantation,bone formation occurred at the interface where the E1001(1k)+CP scaffold was in contact with the bone borders of the implant site.Thereafter,during weeks 6,8 and 12 bone formation progressed throughout the E1001(1k)+CP test implants.This trend was not observed with E1001(1k)+BMM scaffolds or the clinically used BGS.Our results suggest that E1001(1k)+CP should be tested further for osteoregenerative applications.展开更多
基金the Innovative Research Team of Taizhou Polytechnic College(No.TZYTD-16-4)Natural Science Research General Project of Jiangsu Higher Education Institutions(No.18KJD350002)the Doctoral Research Foundation of Taizhou Polytechnic College(No.1322819004).
文摘Focal adhesions are polyproteins linked to extracellular matrix and cytoskeleton,which play an important role in the process of transforming force signals into intracellular chemical signals and subsequently triggering related physiological or pathological reactions.The cytoskeleton is a network of protein fibers in the cytoplasm,which is composed of microfilaments,microtubules,intermediate filaments,and cross-linked proteins.It is a very important structure for cells to maintain their basic morphology.This review summarizes the process of fluid shear stress transduction mediated by focal adhesion and the key role of the cytoskeleton in this process,which focuses on the focal adhesion and cytoskeleton systems.The important proteins involved in signal transduction in focal adhesion are introduced emphatically.The relationship between focal adhesion and mechanical transduction pathways are discussed.In this review,we discuss the relationship between fluid shear stress and associated diseases such as atherosclerosis,as well as its role in clinical research and drug development.
基金This research was sponsored by the Armed Forces Institute of Regenerative Medicine(AFIRM)award number W81XWH-08-2-0034The US Army Medical Research Acquisition Activity,820 Chandler Street,Fort Detrick MD 21702-5014 is the awarding and administering acquisition office。
文摘Next-generation synthetic bone graft therapies will most likely be composed of resorbable polymers in combination with bioactive components.In this article,we continue our exploration of E1001(1k),a tyrosine-derived polycarbonate,as an orthopedic implant material.Specifically,we use E1001(1k),which is degradable,nontoxic,and osteoconductive,to fabricate porous bone regeneration scaffolds that were enhanced by two different types of calcium phosphate(CP)coatings:in one case,pure dicalcium phosphate dihydrate was precipitated on the scaffold surface and throughout its porous structure(E1001(1k)+CP).In the other case,bone matrix minerals(BMM)such as zinc,manganese and fluoride were co-precipitated within the dicalcium phosphate dihydrate coating(E1001(1k)+BMM).These scaffold compositions were compared against each other and against ChronOS(Synthes USA,West Chester,PA,USA),a clinically used bone graft substitute(BGS),which served as the positive control in our experimental design.This BGS is composed of poly(lactide co-e-caprolactone)and beta-tricalcium phosphate.We used the established rabbit calvaria critical-sized defect model to determine bone regeneration within the defect for each of the three scaffold compositions.New bone formation was determined after 2,4,6,8 and 12 weeks by micro-computerized tomography(mCT)and histology.The experimental tyrosine-derived polycarbonate,enhanced with dicalcium phosphate dihydrate,E1001(1k)+CP,supported significant bone formation within the defects and was superior to the same scaffold containing a mix of BMM,E1001(1k)+BMM.The comparison with the commercially available BGS was complicated by the large variability in bone formation observed for the laboratory preparations of E1001(1k)scaffolds.At all time points,there was a trend for E1001(1k)+CP to be superior to the commercial BGS.However,only at the 6-week time point did this trend reach statistical significance.Detailed analysis of the μCT data suggested an increase in bone formation from 2 through 12 weeks in implant sites treated with E1001(1k)+CP.At 2 and 4 weeks post-implantation,bone formation occurred at the interface where the E1001(1k)+CP scaffold was in contact with the bone borders of the implant site.Thereafter,during weeks 6,8 and 12 bone formation progressed throughout the E1001(1k)+CP test implants.This trend was not observed with E1001(1k)+BMM scaffolds or the clinically used BGS.Our results suggest that E1001(1k)+CP should be tested further for osteoregenerative applications.
