Androgenetic alopecia(AGA),the most prevalent clinical hair loss,lacks safe and effective treatments due to downregulated angiogenic genes and insufficient vascularization in the perifollicular microenvironment of the...Androgenetic alopecia(AGA),the most prevalent clinical hair loss,lacks safe and effective treatments due to downregulated angiogenic genes and insufficient vascularization in the perifollicular microenvironment of the bald scalp in AGA patients.In this study,a hyaluronic acid(HA)based hydrogel-formed microneedle(MN)was designed,referred to as V-R-MNs,which was simultaneously loaded with vascular endothelial growth factor(VEGF)and the novel hair loss drug Ritlecitinib,the latter is encapsulated in slowly biodegradable polyhydroxyalkanoates(PHAs)nanoparticles(R-PHA NPs)for minimally invasive AGA treatment.The integration of HA based hydrogel alongside PHA nanoparticles significantly bolstered the mechanical characteristics of microneedles and enhanced skin penetration efficiency.Due to the biosafety,mechanical strength,and controlled degradation properties of HA hydrogel formed microneedles,V-R-MNs can effectively penetrate the skin’s stratum corneum,facilitating the direct delivery of VEGF and Ritlecitinib in a minimally invasive,painless and long-term sustained release manner.V-R-MNs not only promoted angiogenesis and improve the immune microenvironment around the hair follicle to promote the proliferation and development of hair follicle cells,but also the application of MNs to the skin to produce certain mechanical stimulation could also promote angiogenesis.In comparison to the clinical drug minoxidil for AGA treatment,the hair regeneration effect of V-R-MN in AGA model mice is characterized by a rapid onset of the anagen phase,improved hair quality,and greater coverage.This introduces a new,clinically safer,and more efficient strategy for AGA treatment,and serving as a reference for the treatment of other related diseases.展开更多
Infection and rejection in musculoskeletal trauma often pose challenges for natural healing,prompting the exploration of biomimetic organ and tissue transplantation as a common alternative solution.Polyhydroxyalkanoat...Infection and rejection in musculoskeletal trauma often pose challenges for natural healing,prompting the exploration of biomimetic organ and tissue transplantation as a common alternative solution.Polyhydroxyalkanoates(PHAs)are a large family of biopolyesters synthesised in microorganism,demonstrating excellent biocompatibility and controllable biodegradability for tissue remodelling and drug delivery.With different monomer-combination and polymer-types,multi-mechanical properties of PHAs making them have great application prospects in medical devices with stretching,compression,twist in long time,especially in musculoskeletal tissue engineering.This review systematically summarises the applications of PHAs in multiple tissues repair and drug release,encompassing areas such as bone,cartilage,joint,skin,tendons,ligament,cardiovascular tissue,and nervous tissue.It also discusses challenges encountered in their application,including high production costs,potential cytotoxicity,and uncontrollable particle size distribution.In conclusion,PHAs offer a compelling avenue for musculoskeletal system applications,striking a balance between biocompatibility and mechanical performance.However,addressing challenges in their production and application requires further research to unleash their full potential in tackling the complexities of musculoskeletal regeneration.展开更多
基金supported by Grants from National Natural Science Foundation of China(Grant No.s 31900950 and 32000944)the Project Supported by Natural Science Basic Research Plan in Shaanxi Province of China(Grant No.2024JC-YBMS-706)+1 种基金Collaborative Innovation Project of Zigong Medical Big Data and Artificial Intelligence Research Institute(Grant No.2023-YGY-1-02)Key Science and Technology Plan Project of Zigong(Grant No.2022ZCNKY07)。
文摘Androgenetic alopecia(AGA),the most prevalent clinical hair loss,lacks safe and effective treatments due to downregulated angiogenic genes and insufficient vascularization in the perifollicular microenvironment of the bald scalp in AGA patients.In this study,a hyaluronic acid(HA)based hydrogel-formed microneedle(MN)was designed,referred to as V-R-MNs,which was simultaneously loaded with vascular endothelial growth factor(VEGF)and the novel hair loss drug Ritlecitinib,the latter is encapsulated in slowly biodegradable polyhydroxyalkanoates(PHAs)nanoparticles(R-PHA NPs)for minimally invasive AGA treatment.The integration of HA based hydrogel alongside PHA nanoparticles significantly bolstered the mechanical characteristics of microneedles and enhanced skin penetration efficiency.Due to the biosafety,mechanical strength,and controlled degradation properties of HA hydrogel formed microneedles,V-R-MNs can effectively penetrate the skin’s stratum corneum,facilitating the direct delivery of VEGF and Ritlecitinib in a minimally invasive,painless and long-term sustained release manner.V-R-MNs not only promoted angiogenesis and improve the immune microenvironment around the hair follicle to promote the proliferation and development of hair follicle cells,but also the application of MNs to the skin to produce certain mechanical stimulation could also promote angiogenesis.In comparison to the clinical drug minoxidil for AGA treatment,the hair regeneration effect of V-R-MN in AGA model mice is characterized by a rapid onset of the anagen phase,improved hair quality,and greater coverage.This introduces a new,clinically safer,and more efficient strategy for AGA treatment,and serving as a reference for the treatment of other related diseases.
基金the National Natural Science Foundation of China,Nos.31900950 and 32000944 and Key Science and Technology Plan Projects in Zigong,No.2022ZCNKY07.
文摘Infection and rejection in musculoskeletal trauma often pose challenges for natural healing,prompting the exploration of biomimetic organ and tissue transplantation as a common alternative solution.Polyhydroxyalkanoates(PHAs)are a large family of biopolyesters synthesised in microorganism,demonstrating excellent biocompatibility and controllable biodegradability for tissue remodelling and drug delivery.With different monomer-combination and polymer-types,multi-mechanical properties of PHAs making them have great application prospects in medical devices with stretching,compression,twist in long time,especially in musculoskeletal tissue engineering.This review systematically summarises the applications of PHAs in multiple tissues repair and drug release,encompassing areas such as bone,cartilage,joint,skin,tendons,ligament,cardiovascular tissue,and nervous tissue.It also discusses challenges encountered in their application,including high production costs,potential cytotoxicity,and uncontrollable particle size distribution.In conclusion,PHAs offer a compelling avenue for musculoskeletal system applications,striking a balance between biocompatibility and mechanical performance.However,addressing challenges in their production and application requires further research to unleash their full potential in tackling the complexities of musculoskeletal regeneration.
