Tissue regeneration requires structural holding and movement support using tissue-type-specific aids such as bone casts,skin bandages,and joint protectors.Currently,an unmet need exists in aiding breast fat regenerati...Tissue regeneration requires structural holding and movement support using tissue-type-specific aids such as bone casts,skin bandages,and joint protectors.Currently,an unmet need exists in aiding breast fat regeneration as the breast moves following continuous body motion by exposing the breast fat to dynamic stresses.Here,the concept of elastic structural holding is applied to develop a shape-fitting moldable membrane for breast fat regeneration(“adipoconductive”)after surgical defects are made.The membrane has the following key characteristics:(a)It contains a panel of honeycomb structures,thereby efficiently handling motion stress through the entire membrane;(b)a strut is added into each honeycomb in a direction perpendicular to gravity,thereby suppressing the deformation and stress concentration upon lying and standing;and(c)thermo-responsive moldable elastomers are used to support structural holding by suppressing large deviations of movement that occur sporadically.The elastomer became moldable upon a temperature shift above T_(m).The structure can then be fixed as the temperature decreases.As a result,the membrane promotes adipogenesis by activating mechanotransduction in a fat miniature model with pre-adipocyte spheroids under continuous shaking in vitro and in a subcutaneous implant placed on the motion-prone back areas of rodents in vivo.展开更多
Differentiation of human bone marrow-derived mesenchymal stem cells(hMSCs)is regulated by a variety of cues of their surrounding microenvironments.In particular,mechanical properties of cell culture matrices have been...Differentiation of human bone marrow-derived mesenchymal stem cells(hMSCs)is regulated by a variety of cues of their surrounding microenvironments.In particular,mechanical properties of cell culture matrices have been recently disclosed to play a pivotal role in stem cell differentiation.However,it remains elusive how viscosity affects the chondrogenic differentiation of hMSCs during three-dimensional(3 D)culture.In this study,a 3 D culture system that was established by embedding viscous gelatin solution in chemically cross-linked gelatin hydrogels was used for 3 D culture of hMSCs in gelatin solutions with different viscosities.The influence of solution viscosity on chondrogenic differentiation of hMSCs was investigated.Viscous gelatin solutions promoted cell proliferation in the order of low,middle and high viscosity while elastic hydrogels restricted cell proliferation.High viscosity gelatin solution led to increased production of the cartilaginous matrix.Under the synergistic stimulation of chondrogenic induction factors,high viscosity was beneficial for the chondrogenic differentiation of hMSCs.The results suggested the role of viscosity should be considered as one of the dominant mechanical cues affecting stem cell differentiation.展开更多
基金This study was financially supported by the Korea Medical Device Development Fund Grant funded by the Ministry of Science and iCT,the Ministry of Trade,Industry and Energy,the Ministry of Health&Welfare,the Ministry of Food and'Drug Safety(grant nos.1711138302 and KMDF_PR_20200901_0152-01)the National Research Foundation of Korea(NRF)funded by the Korean government(MSIT)(grant nos.2019R1A2C2010802 and 2021R1A6A3A13044778)+1 种基金the Brain Korea 21 PLUS Project for Medical Science of Yonsei Universitythe MD-PhD/Medical Scientist Training Program through the Korea Health Industry Development Institute(KHIDI),funded by the Ministry of Health and Welfare.
文摘Tissue regeneration requires structural holding and movement support using tissue-type-specific aids such as bone casts,skin bandages,and joint protectors.Currently,an unmet need exists in aiding breast fat regeneration as the breast moves following continuous body motion by exposing the breast fat to dynamic stresses.Here,the concept of elastic structural holding is applied to develop a shape-fitting moldable membrane for breast fat regeneration(“adipoconductive”)after surgical defects are made.The membrane has the following key characteristics:(a)It contains a panel of honeycomb structures,thereby efficiently handling motion stress through the entire membrane;(b)a strut is added into each honeycomb in a direction perpendicular to gravity,thereby suppressing the deformation and stress concentration upon lying and standing;and(c)thermo-responsive moldable elastomers are used to support structural holding by suppressing large deviations of movement that occur sporadically.The elastomer became moldable upon a temperature shift above T_(m).The structure can then be fixed as the temperature decreases.As a result,the membrane promotes adipogenesis by activating mechanotransduction in a fat miniature model with pre-adipocyte spheroids under continuous shaking in vitro and in a subcutaneous implant placed on the motion-prone back areas of rodents in vivo.
基金financially supported by JSPS KAKENHI(Nos.18K19947,18K19945 and 19H04475)。
文摘Differentiation of human bone marrow-derived mesenchymal stem cells(hMSCs)is regulated by a variety of cues of their surrounding microenvironments.In particular,mechanical properties of cell culture matrices have been recently disclosed to play a pivotal role in stem cell differentiation.However,it remains elusive how viscosity affects the chondrogenic differentiation of hMSCs during three-dimensional(3 D)culture.In this study,a 3 D culture system that was established by embedding viscous gelatin solution in chemically cross-linked gelatin hydrogels was used for 3 D culture of hMSCs in gelatin solutions with different viscosities.The influence of solution viscosity on chondrogenic differentiation of hMSCs was investigated.Viscous gelatin solutions promoted cell proliferation in the order of low,middle and high viscosity while elastic hydrogels restricted cell proliferation.High viscosity gelatin solution led to increased production of the cartilaginous matrix.Under the synergistic stimulation of chondrogenic induction factors,high viscosity was beneficial for the chondrogenic differentiation of hMSCs.The results suggested the role of viscosity should be considered as one of the dominant mechanical cues affecting stem cell differentiation.