There is no efficient tracking system available for the therapeutic molecules delivered to cartilage.The dense matrix covering the cartilage surface is the main biological barrier that the therapeutic molecules must o...There is no efficient tracking system available for the therapeutic molecules delivered to cartilage.The dense matrix covering the cartilage surface is the main biological barrier that the therapeutic molecules must overcome.In this study,we aimed to establish a system that can dynamically and effectively track the therapeutic molecules delivered to cartilage.To this aim,we adopted bovine and human cartilage explants as ex vivo models for chondrocyte-targeted exosome dispersion.The efficiency of drug delivery was evaluated using frozen sections.The results of this study showed that the penetration and distribution of chondrocyte-targeted exosomes in cartilage explants can be tracked dynamically.Thus,ex vivo cartilage explants provide an effective and economic system to evaluate therapeutic drugs encapsulated in chondrocyte-targeted exosomes in preclinical studies.展开更多
Full-thickness skin wounds are have continued to be reconstructive challenges in dermal and skin appendage regeneration, and skin substitutes are promising tools for addressing these reconstructive procedures. Herein,...Full-thickness skin wounds are have continued to be reconstructive challenges in dermal and skin appendage regeneration, and skin substitutes are promising tools for addressing these reconstructive procedures. Herein, the one-step fabrication of a cell sheet integrated with a biomimetic hydrogel as a tissue engineered skin for skin wound healing generated in one step is introduced. Briefly, cell sheets with rich extracellular matrix, high cell density, and good cell connections were integrated with biomimetic hydrogel to fabricate gel + human skin fibroblasts (HSFs) sheets and gel + human umbilical vein endothelial cells (HUVECs) sheets in one step for assembly as a cell sheet-laden hydrogel (CSH). The designed biomimetic hydrogel formed with UV crosslinking and ionic crosslinking exhibited unique properties due to the photo-generated aldehyde groups, which were suitable for integrating into the cell sheet, and ionic crosslinking reduced the adhesive force toward the substrate. These properties allowed the gel + cell sheet film to be easily released from the substrate. The cells in the harvested cell sheet maintained excellent viability, proliferation, and definite migration abilities inside the hydrogel. Moreover, the CSH was implanted into a full-thickness skin defects to construct a required dermal matrix and cell microenvironment. The wound closure rate reached 60.00 ± 6.26% on the 2nd day, accelerating mature granulation and dermis formation with skin appendages after 14 days. This project can provide distinct guidance and strategies for the complete repair and regeneration of full-thickness skin defects, and provides a material with great potential for tissue regeneration in clinical applications.展开更多
基金National Natural Science Foundation of China(Nos.81972116,81972085,81772394,31900046)Key Program of Natural Science Foundation of Guangdong Province(No.2018B0303110003)+3 种基金Guangdong International Cooperation Project(No.2021A0505030011)Shenzhen Science and Technology Projects(Nos.GJHZ20200731095606019,JCYJ20170817172023838,JCYJ20170306092215436,JCYJ20170413161649437)China Postdoctoral Science Foundation(No.2020M682907)Special Funds for the Construction of High Level Hospitals in Guangdong Province.
文摘There is no efficient tracking system available for the therapeutic molecules delivered to cartilage.The dense matrix covering the cartilage surface is the main biological barrier that the therapeutic molecules must overcome.In this study,we aimed to establish a system that can dynamically and effectively track the therapeutic molecules delivered to cartilage.To this aim,we adopted bovine and human cartilage explants as ex vivo models for chondrocyte-targeted exosome dispersion.The efficiency of drug delivery was evaluated using frozen sections.The results of this study showed that the penetration and distribution of chondrocyte-targeted exosomes in cartilage explants can be tracked dynamically.Thus,ex vivo cartilage explants provide an effective and economic system to evaluate therapeutic drugs encapsulated in chondrocyte-targeted exosomes in preclinical studies.
基金supported by the Shenzhen Basic Research Project Natural Science Foundation(JCYJ20210324103210027)the National Natural Science Foundation of China(No.81771502 and 82273265)+1 种基金the Department of Health of Zhejiang Province(No.2018KY473)PhD Basic Research Initiation Project(RCBS20200714114856171).
文摘Full-thickness skin wounds are have continued to be reconstructive challenges in dermal and skin appendage regeneration, and skin substitutes are promising tools for addressing these reconstructive procedures. Herein, the one-step fabrication of a cell sheet integrated with a biomimetic hydrogel as a tissue engineered skin for skin wound healing generated in one step is introduced. Briefly, cell sheets with rich extracellular matrix, high cell density, and good cell connections were integrated with biomimetic hydrogel to fabricate gel + human skin fibroblasts (HSFs) sheets and gel + human umbilical vein endothelial cells (HUVECs) sheets in one step for assembly as a cell sheet-laden hydrogel (CSH). The designed biomimetic hydrogel formed with UV crosslinking and ionic crosslinking exhibited unique properties due to the photo-generated aldehyde groups, which were suitable for integrating into the cell sheet, and ionic crosslinking reduced the adhesive force toward the substrate. These properties allowed the gel + cell sheet film to be easily released from the substrate. The cells in the harvested cell sheet maintained excellent viability, proliferation, and definite migration abilities inside the hydrogel. Moreover, the CSH was implanted into a full-thickness skin defects to construct a required dermal matrix and cell microenvironment. The wound closure rate reached 60.00 ± 6.26% on the 2nd day, accelerating mature granulation and dermis formation with skin appendages after 14 days. This project can provide distinct guidance and strategies for the complete repair and regeneration of full-thickness skin defects, and provides a material with great potential for tissue regeneration in clinical applications.
