In recent years,the field of mechanomaterials has emerged at the interface of mechanics,materials science,biology,medicine and data science,where materials are proactively designed or programmed to achieve targeted fu...In recent years,the field of mechanomaterials has emerged at the interface of mechanics,materials science,biology,medicine and data science,where materials are proactively designed or programmed to achieve targeted functionalities by leveraging the fundamental mechanics principles and force-geometry-property relationships.In the biological context,one may likewise introduce mechanobiomaterials as a field with the following goals:(1)proactive design or programming of materials for precisely mediating biomechanical environment of living systems for tissue repair/restoration;(2)proactive control/programming of living systems themselves by an external field via force-structure-function relationships.Here,we will discuss an example of research in mechanobiomaterials on using mechanics to guide the design of acellular epicardial patches for the treatment of myocardial infarction.This technology aims to employ a biocompatible material patch to help reverse left ventricular remodeling and restore heart function after myocardial infarction by increasing the mechanical integrity of damaged heart tissues.However,its application is currently limited by widely scattered therapeutic efficacy.Here,we develop a biomechanics-based simulation platform that allows us to test,design and optimize the performance of an epicardial patch.We show that the widely scattered therapeutic efficacy of this technology can be attributed to a“pre-strain sensitivity”caused by attaching an elastic patch to a dynamically beating heart.To mitigate this challenge,we introduce a viscoelastic epicardial patch,designed at the so-called‘gel point’of the material,that effectively accommodates the cyclic deformation of the myocardium.This then leads to the fabrication and experimentally validated epicardial patch that outperforms all existing ones in restoring heart function after both acute and subacute myocardial infarction in rats.Our study also demonstrates the potential of employing viscoelastic interfaces for better integration of synthetic materials with biological tissues.展开更多
Objective:Drug-loaded mucoadhesive silk fibroin(SF)microneedle patch can overcome the limitations of low bioavailability and significant pain associated with traditional treatment methods,such as topical application o...Objective:Drug-loaded mucoadhesive silk fibroin(SF)microneedle patch can overcome the limitations of low bioavailability and significant pain associated with traditional treatment methods,such as topical application or injection of triamcinolone for oral submucous fibrosis(OSF).However,these systems release the drug too quickly,failing to meet the clinical requirements.This study aims to construct a mucoadhesive SF microneedle patch pre-assembled with silk fibroin nanospheres(SFN)and explore its ability to sustain the release of triamcinolone in the treatment of OSF.Methods:SFN was pre-assembled via precipitation reaction and characterized by scanning electron microscope(SEM)for the morphology.The particle size andζ-potential were measured by dynamic light scattering(DLS).Triamcinolone was loaded onto SFN using a diffusional post-loading method.The effective loading of triamcinolone was confirmed using Fourier-transform infrared spectroscopy(FTIR).The concentration of unloaded triamcinolone was quantified by high-performance liquid chromatography.Drug encapsulation efficiency and loading capacity of SFN were then calculated to determine the optimal amount of drug loading.The SFN suspension was pre-mixed with SF solution to prepare the microneedle under-layer.The microneedle morphology was observed by SEM.Compression mechanical tests were performed to evaluate the fracture force of microneedles at different nanosphere contents(5%,10%,and 20%),determining the optimal pre-mixing ratio.Ex-vivo mouse oral mucosa permeation studies were performed to ascertain the insertion depth of the microneedles via histological sections.The adhesive top layer was synthesized using SF and tannic acid,with FTIR confirming its successful synthesis.Its viscoelasticity was characterized by a rheometer,and differential scanning calorimetry analyzed thermal properties.Tensile tests evaluated the interfacial bonding strength between the adhesive layer and microneedle base to ensure no detachment during use.Adhesion to wet oral mucosal tissues was tested and compared to commercial oral patches.Under the optimized conditions,the double-layered mucoadhesive microneedle patch with pre-assembled nanospheres was prepared.Its cell compatibility was evaluated by cell counting kit-8(CCK-8),live/dead staining,and phalloidin staining after co culturing with fibroblasts.The drug release experiment was conducted to demonstrate its sustained release efficacy.Results:SFN(mean diameter 46.25 nm)was successfully prepared.The maximum drug encapsulation efficiency was(63.88±1.09)%(corresponding loading capacity of SFN was(27.41±3.06)%when the weight ratio of triamcinolone/SFN was 0.5.The corporation of SFN did not affect microneedle morphology.The mechanical properties of microneedles decreased with increasing nanosphere amount.Only the fracture force of the group with 5%SFN[(0.07±0.01)N/needle]exceeded the minimum force required for mucosal penetration,thus selected as the optimal pre-mixing ratio.Histological sections confirmed that the SFN microneedles could penetrate the epithelial layer and deliver drugs to OSF affected areas.Adhesion strength between the microneedle base and top layer was(94.8±6.89)kPa,confirming strong bonding with no detachment during use.The wet adhesive strength of the double-layered mucoadhesive microneedle patch[(41.28±7.43)kPa]was significantly enhanced compared to commercial oral patches(4.5 kPa,P<0.01).CCK-8 and live/dead staining results confirmed no significant cytotoxicity.Drug release experiment showed the double-layered mucoadhesive microneedle patch with pre-assembled SFN enabled sustained release time of triamcinolone from 4 days to 14 days.Conclusion:Pre-assembling nanospheres in mucoadhesive SF microneedle patches can extend triamcinolone release time,meeting clinical requirements for sustained drug delivery.展开更多
文摘In recent years,the field of mechanomaterials has emerged at the interface of mechanics,materials science,biology,medicine and data science,where materials are proactively designed or programmed to achieve targeted functionalities by leveraging the fundamental mechanics principles and force-geometry-property relationships.In the biological context,one may likewise introduce mechanobiomaterials as a field with the following goals:(1)proactive design or programming of materials for precisely mediating biomechanical environment of living systems for tissue repair/restoration;(2)proactive control/programming of living systems themselves by an external field via force-structure-function relationships.Here,we will discuss an example of research in mechanobiomaterials on using mechanics to guide the design of acellular epicardial patches for the treatment of myocardial infarction.This technology aims to employ a biocompatible material patch to help reverse left ventricular remodeling and restore heart function after myocardial infarction by increasing the mechanical integrity of damaged heart tissues.However,its application is currently limited by widely scattered therapeutic efficacy.Here,we develop a biomechanics-based simulation platform that allows us to test,design and optimize the performance of an epicardial patch.We show that the widely scattered therapeutic efficacy of this technology can be attributed to a“pre-strain sensitivity”caused by attaching an elastic patch to a dynamically beating heart.To mitigate this challenge,we introduce a viscoelastic epicardial patch,designed at the so-called‘gel point’of the material,that effectively accommodates the cyclic deformation of the myocardium.This then leads to the fabrication and experimentally validated epicardial patch that outperforms all existing ones in restoring heart function after both acute and subacute myocardial infarction in rats.Our study also demonstrates the potential of employing viscoelastic interfaces for better integration of synthetic materials with biological tissues.
基金supported by the National Key Research and Development Program(2022YFC2402900)the Key Research and Development Program of Hainan Province(ZDYF2024SHFZ128)the Science and Technology Innovation Program of Hunan Province(2022RC1213),China.
文摘Objective:Drug-loaded mucoadhesive silk fibroin(SF)microneedle patch can overcome the limitations of low bioavailability and significant pain associated with traditional treatment methods,such as topical application or injection of triamcinolone for oral submucous fibrosis(OSF).However,these systems release the drug too quickly,failing to meet the clinical requirements.This study aims to construct a mucoadhesive SF microneedle patch pre-assembled with silk fibroin nanospheres(SFN)and explore its ability to sustain the release of triamcinolone in the treatment of OSF.Methods:SFN was pre-assembled via precipitation reaction and characterized by scanning electron microscope(SEM)for the morphology.The particle size andζ-potential were measured by dynamic light scattering(DLS).Triamcinolone was loaded onto SFN using a diffusional post-loading method.The effective loading of triamcinolone was confirmed using Fourier-transform infrared spectroscopy(FTIR).The concentration of unloaded triamcinolone was quantified by high-performance liquid chromatography.Drug encapsulation efficiency and loading capacity of SFN were then calculated to determine the optimal amount of drug loading.The SFN suspension was pre-mixed with SF solution to prepare the microneedle under-layer.The microneedle morphology was observed by SEM.Compression mechanical tests were performed to evaluate the fracture force of microneedles at different nanosphere contents(5%,10%,and 20%),determining the optimal pre-mixing ratio.Ex-vivo mouse oral mucosa permeation studies were performed to ascertain the insertion depth of the microneedles via histological sections.The adhesive top layer was synthesized using SF and tannic acid,with FTIR confirming its successful synthesis.Its viscoelasticity was characterized by a rheometer,and differential scanning calorimetry analyzed thermal properties.Tensile tests evaluated the interfacial bonding strength between the adhesive layer and microneedle base to ensure no detachment during use.Adhesion to wet oral mucosal tissues was tested and compared to commercial oral patches.Under the optimized conditions,the double-layered mucoadhesive microneedle patch with pre-assembled nanospheres was prepared.Its cell compatibility was evaluated by cell counting kit-8(CCK-8),live/dead staining,and phalloidin staining after co culturing with fibroblasts.The drug release experiment was conducted to demonstrate its sustained release efficacy.Results:SFN(mean diameter 46.25 nm)was successfully prepared.The maximum drug encapsulation efficiency was(63.88±1.09)%(corresponding loading capacity of SFN was(27.41±3.06)%when the weight ratio of triamcinolone/SFN was 0.5.The corporation of SFN did not affect microneedle morphology.The mechanical properties of microneedles decreased with increasing nanosphere amount.Only the fracture force of the group with 5%SFN[(0.07±0.01)N/needle]exceeded the minimum force required for mucosal penetration,thus selected as the optimal pre-mixing ratio.Histological sections confirmed that the SFN microneedles could penetrate the epithelial layer and deliver drugs to OSF affected areas.Adhesion strength between the microneedle base and top layer was(94.8±6.89)kPa,confirming strong bonding with no detachment during use.The wet adhesive strength of the double-layered mucoadhesive microneedle patch[(41.28±7.43)kPa]was significantly enhanced compared to commercial oral patches(4.5 kPa,P<0.01).CCK-8 and live/dead staining results confirmed no significant cytotoxicity.Drug release experiment showed the double-layered mucoadhesive microneedle patch with pre-assembled SFN enabled sustained release time of triamcinolone from 4 days to 14 days.Conclusion:Pre-assembling nanospheres in mucoadhesive SF microneedle patches can extend triamcinolone release time,meeting clinical requirements for sustained drug delivery.
