Recent Progress in Cartilage Tissue Engineering--Our Experience and Future Directions

Given the limited spontaneous repair that follows cartilage injury, demand is growing for tissue engi- neering approaches for cartilage regeneration. There are two major applications for tissue-engineered cartilage. One is in orthopedic surgery, in which the engineered cartilage is usually used to repair cartilage defects or loss in an articular joint or meniscus in order to restore the joint function. The other is for head and neck reconstruction, in which the engineered cartilage is usually applied to repair cartilage defects or loss in an auricle, trachea, nose, larynx, or eyelid. The challenges faced by the engineered car- tilage for one application are quite different from those faced by the engineered cartilage for the other application. As a result, the emphases of the engineering strategies to generate cartilage are usually quite different for each application. The statuses of preclinical animal investigations and of the clinical translation of engineered cartilage are also at different levels for each application. The aim of this review is to provide an opinion piece on the challenges, current developments, and future directions for cartilage engineering for both applications.

Eco-friendly glucose assisted structurally simplified high-efficiency tin-lead mixed perovskite solar cells

Achieving highly-efficient and stable perovskite solar cells(PSCs) with a simplified structure remains challenging, despite the tremendous potential for reducing preparation cost and facile processability by removing hole transport layer(HTL). In this work, eco-friendly glucose(Gl) as an interface modifier for HTL-free narrow bandgap tin-lead(Sn-Pb) PSCs is proposed. Gl not only enhances the wettability of the indium tin oxide to promote perovskite heterogeneous nucleation on substrate, but also realizes defect passivation by interacting with uncoordinated Pb^(2+) and Sn^(2+) in perovskite films. As a result, the quality of the perovskite films has been significantly improved, accompanied by reduced defects of bottom interface and optimized energy level structure of device, leading to an efficiency increase and a less nonradiative voltage loss of 0.102 V(for a bandgap of ~1.26 eV). Consequently, the optimized PSC delivers an unprecedented efficiency over 21% with high open-circuit voltage and enhanced stability, outperforming the control device. This work demonstrates a cost-effective approach to develop simplified structure high efficiency HTL-free Sn-Pb PSC.

Enhancing cartilage regeneration and repair through bioactive and biomechanical modification of 3D acellular dermal matrix

Acellular dermal matrix(ADM)shows promise for cartilage regeneration and repair.However,an effective decellularization technique that removes cellular components while preserving the extracellular matrix,the transformation of 2D-ADM into a suitable 3D scaffold with porosity and the enhancement of bioactive and biomechanical properties in the 3D-ADM scaffold are yet to be fully addressed.In this study,we present an innovative decellularization method involving 0.125%trypsin and 0.5%SDS and a 1%Triton X-100 solution for preparing ADM and converting 2D-ADM into 3D-ADM scaffolds.These scaffolds exhibit favorable physicochemical properties,exceptional biocompatibility and significant potential for driving cartilage regeneration in vitro and in vivo.To further enhance the cartilage regeneration potential of 3D-ADM scaffolds.we incorporated porcine-derived small intestinal submucosa(SIS)for bioactivity and calcium sulfate hemihydrate(CSH)for biomechanical reinforcement.The resulting 3D-ADM+SIS scaffolds displayed heightened biological activity,while the 3D-ADM+CSH scaffolds notably bolstered biomechanical strength.Both scaffold types showed promise for cartilage regeneration and repair in vitro and in vivo,with considerable improvements observed in repairing cartilage defects within a rabbit articular cartilage model.In summary,this research introduces a versatile 3D-ADM scaffold with customizable bioactive and biomechanical properties,poised to revolutionize the field of cartilageregeneration.

Mechanically skin-like and water-resistant self-healing bioelastomer for high-tension wound healing

The biomedical application of self-healing materials in wet or(under)water environments is quite challenging because the insulation and dissociation effects of water molecules significantly reduce the reconstruction of material–interface interactions.Rapid closure with uniform tension of high-tension wounds is often difficult,leading to further deterioration and scarring.Herein,a new type of thermosetting water-resistant self-healing bioelastomer(WRSHE)was designed by synergistically incorporating a stable polyglycerol sebacate(PGS)covalent crosslinking network and triple hybrid dynamic networks consisting of reversible disulfide metathesis(SS),and dimethylglyoxime urethane(Dou)and hydrogen bonds.And a resveratrol-loaded WRSHE(Res@WRSHE)was developed by a swelling,absorption,and crosslinked network locking strategy.WRSHEs exhibited skin-like mechanical properties in terms of nonlinear modulus behavior,biomimetic softness,high stretchability,and good elasticity,and they also achieved ultrafast and highly efficient self-healing in various liquid environments.For wound-healing applications of high-tension full-thickness skin defects,the convenient surface assembly by self-healing of WRSHEs provides uniform contraction stress to facilitate tight closure.Moreover,Res@WRSHEs gradually release resveratrol,which helps inflammatory response reduction,promotes blood vessel regeneration,and accelerates wound repair.

Instant trachea reconstruction using 3D-bioprinted C-shape biomimetic trachea based on tissue-specific matrix hydrogels

Currently,3D-bioprinting technique has emerged as a promising strategy to offer native-like tracheal substitutes for segmental trachea reconstruction.However,there has been very limited breakthrough in tracheal repair using 3D-bioprinted biomimetic trachea owing to the lack of ideal bioinks,the requirement for precise structural biomimicking,and the complexity of multi-step surgical procedures by mean of intramuscular pre-implantation.Herein,we propose a one-step surgical technique,namely direct end-to-end anastomosis using C-shape 3D-bioprinted biomimetic trachea,for segmental trachea defect repair.First,two types of tissue-specific matrix hydrogels were exploited to provide mechanical and biological microenvironment conducive to the specific growth ways of cartilage and fibrous tissue respectively.In contrast to our previous O-shape tracheal design,the tubular structure of alternating C-shape cartilage rings and connecting vascularized-fibrous-tissue rings was meticulously designed for rapid 3D-bioprinting of tracheal constructs with optimal printing paths and models.Furthermore,in vivo trachea regeneration in nude mice showed satisfactory mechanical adaptability and efficient physiological regeneration.Finally,in situ segmental trachea reconstruction by direct end-to-end anastomosis in rabbits was successfully achieved using 3D-bioprinted C-shape biomimetic trachea.This study demonstrates the potential of advanced 3D-bioprinting for instant and efficient repair of segmental trachea defects.

Bioprinting and regeneration of auricular cartilage using a bioactive bioink based on microporous photocrosslinkable acellular cartilage matrix

Tissue engineering provides a promising strategy for auricular reconstruction.Although the first international clinical breakthrough of tissue-engineered auricular reconstruction has been realized based on polymer scaffolds,this approach has not been recognized as a clinically available treatment because of its unsatisfactory clinical efficacy.This is mainly since reconstruction constructs easily cause inflammation and deformation.In this study,we present a novel strategy for the development of biological auricle equivalents with precise shapes,low immunogenicity,and excellent mechanics using auricular chondrocytes and a bioactive bioink based on biomimetic microporous methacrylate-modified acellular cartilage matrix(ACMMA)with the assistance of gelatin methacrylate(GelMA),poly(ethylene oxide)(PEO),and polycaprolactone(PCL)by integrating multi-nozzle bioprinting technology.Photocrosslinkable ACMMA is used to emulate the intricacy of the cartilage-specific microenvironment for active cellular behavior,while GelMA,PEO,and PCL are used to balance printability and physical properties for precise structural stability,form the microporous structure for unhindered nutrient exchange,and provide mechanical support for higher shape fidelity,respectively.Finally,mature auricular cartilage-like tissues with high morphological fidelity,excellent elasticity,abundant cartilage lacunae,and cartilage-specific ECM deposition are successfully regenerated in vivo,which provides new opportunities and novel strategies for the fabrication and regeneration of patient-specific auricular cartilage.

Large-sized bone defect repair by combining a decalcified bone matrix framework and bone regeneration units based on photo-crosslinkable osteogenic microgels

Physiological repair of large-sized bone defects is great challenging in clinic due to a lack of ideal grafts suitable for bone regeneration.Decalcified bone matrix(DBM)is considered as an ideal bone regeneration scaffold,but low cell seeding efficiency and a poor osteoinductive microenvironment greatly restrict its application in large-sized bone regeneration.To address these problems,we proposed a novel strategy of bone regeneration units(BRUs)based on microgels produced by photo-crosslinkable and microfluidic techniques,containing both the osteogenic ingredient DBM and vascular endothelial growth factor(VEGF)for accurate biomimic of an osteoinductive microenvironment.The physicochemical properties of microgels could be precisely controlled and the microgels effectively promoted adhesion,proliferation,and osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)in vitro.BRUs were successfully constructed by seeding BMSCs onto microgels,which achieved reliable bone regeneration in vivo.Finally,by integrating the advantages of BRUs in bone regeneration and the advantages of DBM scaffolds in 3D morphology and mechanical strength,a BRU-loaded DBM framework successfully regenerated bone tissue with the desired 3D morphology and effectively repaired a large-sized bone defect of rabbit tibia.The current study developed an ideal bone biomimetic microcarrier and provided a novel strategy for bone regeneration and large-sized bone defect repair.

Reaction mechanism of arsenic capture by a calcium-based sorbent during the combustion of arsenic-contaminated biomass: A pilot-scale experience

Large quantities of contaminated biomass due to phytoremediation were disposed through combustion in low-income rural regions of China.This process provided a solution to reduce waste volume and disposal cost.Pilot-scale combustion trials were conducted for in site disposal at phytoremediation sites.The reaction mechanism of arsenic capture during pilot-scale combustion should be determined to control the arsenic emission in flue gas.This study investigated three Pteris vittata L.biomass with a disposal capacity of 600 kg/d and different arsenic concentrations from three sites in China.The arsenic concentration in flue gas was greater than that of the national standard in the trial with no emission control,and the arsenic concentration in biomass was 486 mg/kg.CaO addition notably reduced arsenic emission in flue gas,and absorption was efficient when CaO was mixed with biomass at 10% of the total weight.For the trial with 10% CaO addition,arsenic recovery from ash reached 76%,which is an ~8-fold increase compared with the control.Synchrotron radiation analysis confirmed that calcium arsenate is the dominant reaction product.

Moisture influence in emerging neuromorphic device

Conduction filament formation,redox reaction,and mobile ion migration in solid electrolytes underpin the memristive devices,all of which are partially influenced or fully dominated by the moisture.The moisture-based physical-chemistry mechanism provides an electric tunable method to create enough dissociate conductance states for neuromorphic computing,but overconcentration moisture will corrode electrode and then causes device invalidation.This perspective goal is that surveys the moisture-dependency of dynamic at interfaces or/and switching function layer,clarifies the bottlenecks that the memristive device facing in terms of water molecule-related reaction,and gives the possible solutions.

Dominant role of in situ native cartilage niche for determining the cartilage type regenerated by BMSCs

Tissue-engineered cartilage regeneration by bone marrow stromal cells(BMSCs)is considered an ideal method.However,how to regulate BMSCs to regenerate specific types of cartilage remains unclear,which significantly limits its clinical translation and leads to suboptimal clinical effects.Herein,we systematically explored the role of native ear and articular cartilage niches on the differentiation fate of BMSCs and the type of regenerated cartilage.First,we prepared two types of acellular cartilage sheets(ACSs)and two types of chondrocytes.Then green fluorescent protein-labeled BMSCs were seeded on two types of ACSs with or without corresponding types of chondrocytes using a sandwich model and directed or cross-implanted them into native cartilage niches.After one year of in vivo culture,cell tracking and the results of histological results showed that the native cartilage niches were capable of regulating BMSCs regeneration into specific types of cartilage that were consistent with the cartilage types of the implanted sites.Furthermore,even when the type of niche formed by ACSs or the biomimetic cartilage niche constructed by specific types of ACSs and specific types of chondrocytes did not match with the native cartilage niche,the native cartilage niche continued to determine the type of cartilage regenerated by implanted BMSCs and chondrocytes.All our results provide sufficient evidence for specific types of cartilage regeneration using chondrogenic potential cells,such as mesenchymal stem cells and chondrocytes.

4-Axis printing microfibrous tubular scaffold and tracheal cartilage application

Long-segment defects remain a major problem in clinical treatment of tubular tissue reconstruction.The design of tubular scaffold with desired structure and functional properties suitable for tubular tissue regeneration remains a great challenge in regenerative medicine.Here,we present a reliable method to rapidly fabricate tissueengineered tubular scaffold with hierarchical structure via 4-axis printing system.The fabrication process can be adapted to various biomaterials including hydrogels,thermoplastic materials and thermosetting materials.Using polycaprolactone(PCL)as an example,we successfully fabricated the scaffolds with tunable tubular architecture,controllable mesh structure,radial elasticity,good flexibility,and luminal patency.As a preliminary demonstration of the applications of this technology,we prepared a hybrid tubular scaffold via the combination of the 4-axis printed elastic poly(glycerol sebacate)(PGS)bio-spring and electrospun gelatin nanofibers.The scaffolds seeded with chondrocytes formed tubular mature cartilage-like tissue both via in vitro culture and subcutaneous implantation in the nude mouse,which showed great potential for tracheal cartilage reconstruction.

Tissue engineering of cartilage,tendon and bone

Tissue engineering aims to produce a functional tissue replacement to repair defects.Tissue reconstruction is an essential step toward the clinical application of engineered tissues.Significant progress has recently been achieved in this field.In our laboratory,we focus on construction of cartilage,tendon and bone.The purpose of this review was to summarize the advances in the engineering of these three tissues,particularly focusing on tissue regeneration and defect repair in our laboratory.In cartilage engineering,articular cartilage was reconstructed and defects were repaired in animal models.More sophisticated tissues,such as cartilage in the ear and trachea,were reconstructed both in vitro and in vivo with specific shapes and sizes.Engineered tendon was generated in vitro and in vivo in many animal models with tenocytes or dermal fibroblasts in combination with appropriate mechanical loading.Cranial and limb bone defects were also successfully regenerated and repaired in large animals.Based on sophisticated animal studies,several clinical trials of engineered bone have been launched with promising preliminary results,displaying the high potential for clinical application.

Elastic Fiber‑Reinforced Silk Fibroin Scaffold with A Double‑Crosslinking Network for Human Ear‑Shaped Cartilage Regeneration

Tissue engineering provides a promising approach for regenerative medicine.The ideal engineered tissue should have the desired structure and functional properties suitable for uniform cell distribution and stable shape fidelity in the full period of in vitro culture and in vivo implantation.However,due to insufficient cell infiltration and inadequate mechanical properties,engineered tissue made from porous scaffolds may have an inconsistent cellular composition and a poor shape retainability,which seriously hinders their further clinical application.In this study,silk fibroin was integrated with silk short fibers with a physical and chemical double-crosslinking network to fabricate fiber-reinforced silk fibroin super elastic absorbent sponges(Fr-SF-SEAs).The Fr-SF-SEAs exhibited the desirable synergistic properties of a honeycomb structure,hygroscopicity and elasticity,which allowed them to undergo an unconventional cyclic compression inoculation method to significantly promote cell diffusion and achieve a uniform cell distribution at a high-density.Furthermore,the regenerated cartilage of the Fr-SF-SEAs scaffold withstood a dynamic pressure environment after subcutaneous implantation and maintained its precise original structure,ultimately achieving human-scale ear-shaped cartilage regeneration.Importantly,the SF-SEAs prepara-tion showed valuable universality in combining chemicals with other bioactive materials or drugs with reactive groups to construct microenvironment bionic scaffolds.The established novel cell inoculation method is highly versatile and can be readily applied to various cells.Based on the design concept of dual-network Fr-SF-SEAs scaffolds,homogenous and mature cartilage was successfully regenerated with precise and complicated shapes,which hopefully provides a platform strategy for tissue engineering for various cartilage defect repairs.

Chondrogenic medium in combination with a c-Jun N-terminal kinase inhibitor mediates engineered cartilage regeneration by regulating matrix metabolism and cell proliferation

Cartilage tissue engineering is a promising strategy for repairing cartilage defects.However,achieving satisfactory cartilage regeneration in vitro and maintaining its stability in vivo remains a challenge.The key to achieving this goal is establishing an efficient cartilage regeneration culture system to retain sufficient active cells with physiological functions,generate abundant cartilage extracellular matrix(ECM)and maintain a low level of cartilage ECM degradation.The current chondrogenic medium(CM)can effectively promote cartilage ECM production;however,it has a negative effect on cell proliferation.Meanwhile,the specific c-Jun N-terminal kinase pathway inhibitor SP600125 promotes chondrocyte proliferation but inhibits ECM synthesis.Here,we aimed to construct a three-dimensional cartilage regeneration model using a polyglycolic acid/polylactic acid scaffold in combination with chondrocytes to investigate the effect of different culture modes with CM and SP600125 on in vitro cartilage regeneration and their long-term outcomes in vivo systematically.Our results demonstrate that the long-term combination of CM and SP600125 made up for each other and maximized their respective advantages to obtain optimal cartilage regeneration in vitro.Moreover,the long-term combination achieved stable cartilage regeneration after implantation in vivo with a relatively low initial cell-seeding concentration.Therefore,the long-term combination of CM and SP600125 enhanced in vitro and in vivo cartilage regeneration stability with fewer initial seeding cells and thus optimized the cartilage regeneration culture system.