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The changing climate poses a growing challenge to the population health. The objective of this study was to assess the association between ambient temperature and cause-specific mortality in Suzhou. Based on the non-accidental mortality data collected during 2008-2022 in Suzhou, China, this study utilized an individual-level case-crossover design to evaluate the associations of temperature with cause-specific mortality. We applied a distributed lag nonlinear model with a maximum lag of 14 days to account for lag effects. Mortality risk due to extreme cold (<2.5th percentile) and extreme heat (>97.5th percentile) was analyzed. A total of 634,530 non-accidental deaths were analyzed in this study. An inverse J-shaped exposure-response relationship was observed between ambient temperature and non-accidental mortality, with the minimum mortality temperature (MMT) at 29.1â. The relative risk (RR) of mortality associated with extreme cold (2.5th percentile) was 1.37 [95â¯% confidence interval (CI): 1.30, 1.44], higher than estimate of 1.09 (95â¯%CI: 1.07, 1.11) for extreme heat (97.5th percentile) relative to the MMT. Heat effect lasted for 2-3 days, while cold effect could persist for almost 14 days. Higher mortality risk estimates were observed for cardiorespiratory deaths compared to total deaths, with statistically significant between-group differences. Consequently, this study provides first-hand evidence on the associations between ambient temperatures and mortality risks from various causes, which could help local government and policy-makers in designing targeted strategies and public health measures against the menace of climate change.
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Estudos Cross-Over , China/epidemiologia , Humanos , Feminino , Masculino , Mortalidade/tendências , Pessoa de Meia-Idade , Mudança Climática , Adulto , Temperatura , Exposição Ambiental/estatística & dados numéricos , Exposição Ambiental/efeitos adversos , Idoso , Causas de Morte , Adulto Jovem , Calor Extremo/efeitos adversosRESUMO
OBJECTIVE: Socioeconomic status (SES) has been proven to be associated with chronic obstructive pulmonary disease (COPD) in Western populations, but the evidence is very limited in China. This study aimed to investigate the association between SES and the risk of COPD incident. METHODS: This study was based on the China Kadoorie Biobank (CKB) project in Wuzhong District, Suzhou. A total of 45,484 adults aged 30-79 were included in the analysis during 2004-2008. We used Cox proportional hazard models to investigate the association between SES and the risk of COPD. Household income, education, private property and consumption potential was used to measure SES. Incident COPD cases were ascertained using hospitalization records, death certificates, and active follow-up. RESULTS: A total of 524 COPD cases were identified during a median follow-up of 11.2 years. Household income was inversely associated with the risk of COPD (Ptrend<0.005). The adjusted hazard ratios (95% confidence intervals) for incident COPD were 0.88 (0.69-1.14), 0.77 (0.60-0.99), and 0.42 (0.31-0.57) for participants with annual household income of 10,000 ~ 19,999 yuan, 20,000 ~ 34,999 yuan and ≥ 35,000 yuan respectively, in comparison to participants with an annual household income < 10,000 yuan. Furthermore, we found that education level, refrigerator use, private toilet, private phone, and motor vehicle were adversely associated with COPD risk, while ownership of newly renovated flats was positively correlated with COPD incident. CONCLUSIONS: This prospective study suggests that SES is associated with the risk of COPD in Chinese adults. Population-based COPD prevention strategies tailored for people with different SES could help reduce the burden of COPD in Chinese.
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Doença Pulmonar Obstrutiva Crônica , Classe Social , Humanos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , China/epidemiologia , Pessoa de Meia-Idade , Masculino , Feminino , Estudos Prospectivos , Adulto , Idoso , Fatores de Risco , Modelos de Riscos Proporcionais , IncidênciaRESUMO
Objectives: The characteristics of multimorbidity in the Chinese population are currently unclear. We aimed to determine the temporal change in multimorbidity prevalence, clustering patterns, and the association of multimorbidity with mortality from all causes and four major chronic diseases. Methods: This study analyzed data from the China Kadoorie Biobank study performed in Wuzhong District, Jiangsu Province. A total of 53,269 participants aged 30-79 years were recruited between 2004 and 2008. New diagnoses of 15 chronic diseases and death events were collected during the mean follow-up of 10.9 years. Yule's Q cluster analysis method was used to determine the clustering patterns of multimorbidity. A Cox proportional hazards model was used to estimate the associations of multimorbidity with mortalities. Results: The overall multimorbidity prevalence rate was 21.1% at baseline and 27.7% at the end of follow-up. Multimorbidity increased more rapidly during the follow-up in individuals who had a higher risk at baseline. Three main multimorbidity patterns were identified: (i) cardiometabolic multimorbidity (diabetes, coronary heart disease, stroke, and hypertension), (ii) respiratory multimorbidity (tuberculosis, asthma, and chronic obstructive pulmonary disease), and (iii) mental, kidney and arthritis multimorbidity (neurasthenia, psychiatric disorders, chronic kidney disease, and rheumatoid arthritis). There were 3,433 deaths during the follow-up. The mortality risk increased by 24% with each additional disease [hazard ratio (HR) = 1.24, 95% confidence interval (CI) = 1.20-1.29]. Compared with those without multimorbidity at baseline, both cardiometabolic multimorbidity and respiratory multimorbidity were associated with increased mortality from all causes and four major chronic diseases. Cardiometabolic multimorbidity was additionally associated with mortality from cardiovascular diseases and diabetes, with HRs of 2.64 (95% CI = 2.19-3.19) and 28.19 (95% CI = 14.85-53.51), respectively. Respiratory multimorbidity was associated with respiratory disease mortality, with an HR of 9.76 (95% CI = 6.22-15.31). Conclusion: The prevalence of multimorbidity has increased substantially over the past decade. This study has revealed that cardiometabolic multimorbidity and respiratory multimorbidity have significantly increased mortality rates. These findings indicate the need to consider high-risk populations and to provide local evidence for intervention strategies and health management in economically developed regions.
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Multimorbidade , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , China/epidemiologia , Idoso , Prevalência , Adulto , Análise por Conglomerados , Doença Crônica/epidemiologia , Doença Crônica/mortalidade , Modelos de Riscos Proporcionais , Bancos de Espécimes Biológicos , Mortalidade/tendências , Fatores de RiscoRESUMO
Commonly, articular osteochondral tissue exists significant differences in physiological architecture, mechanical function, and biological microenvironment. However, the development of biomimetic scaffolds incorporating upper cartilage, middle tidemark-like, and lower subchondral bone layers for precise articular osteochondral repair remains elusive. This study proposed here a novel strategy to construct the trilayered biomimetic hydrogel scaffolds with dual-differential microenvironment of both mechanical and biological factors. The cartilage-specific microenvironment was achieved through the grafting of kartogenin (KGN) into gelatin via p-hydroxyphenylpropionic acid (HPA)-based enzyme crosslinking reaction as the upper cartilage layer. The bone-specific microenvironment was achieved through the grafting of atorvastatin (AT) into gelatin via dual-crosslinked network of both HP-based enzyme crosslinking and glycidyl methacrylate (GMA)-based photo-crosslinking reactions as the lower subchondral bone layer. The introduction of tidemark-like middle layer is conducive to the formation of well-defined cartilage-bone integrated architecture. The in vitro experiments demonstrated the significant mechanical difference of three layers, successful grafting of drugs, good cytocompatibility and tissue-specific induced function. The results of in vivo experiments also confirmed the mechanical difference of the trilayered bionic scaffold and the ability of inducing osteogenesis and chondrogenesis. Furthermore, the articular osteochondral defects were successfully repaired using the trilayered biomimetic hydrogel scaffolds by the activation of endogenous recovery, which offers a promising alternative for future clinical treatment.
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Tissue-engineered bone has emerged as a promising alternative for bone defect repair due to the advantages of regenerative bone healing and physiological functional reconstruction. However, there is very limited breakthrough in achieving favorable bone regeneration due to the harsh osteogenic microenvironment after bone injury, especially the avascular and hypoxic conditions. Inspired by the bone developmental mode of endochondral ossification, a novel strategy is proposed for tolerant and rapid endochondral bone regeneration using framework-enhanced 3D biomineralized matrix hydrogels. First, it is meticulously designed 3D biomimetic hydrogels with both hypoxic and osteoinductive microenvironment, and then integrated 3D-printed polycaprolactone framework to improve their mechanical strength and structural fidelity. The inherent hypoxic 3D matrix microenvironment effectively activates bone marrow mesenchymal stem cells self-regulation for early-stage chondrogenesis via TGFß/Smad signaling pathway due to the obstacle of aerobic respiration. Meanwhile, the strong biomineralized microenvironment, created by a hybrid formulation of native-constitute osteogenic inorganic salts, can synergistically regulate both bone mineralization and osteoclastic differentiation, and thus accelerate the late-stage bone maturation. Furthermore, both in vivo ectopic osteogenesis and in situ skull defect repair successfully verified the high efficiency and mechanical maintenance of endochondral bone regeneration mode, which offers a promising treatment for craniofacial bone defect repair.
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Osso e Ossos , Hidrogéis , Osteogênese , Regeneração Óssea , Engenharia TecidualRESUMO
The harsh urethral microenvironment (UME) after trauma severely hinders the current hydrogel-based urethral repair. In fact, four-dimensional (4D) consideration to mimic time-dependent physiological processes is essential for scarless urethral reconstruction, which requires balancing extracellular matrix (ECM) deposition and remodeling at different healing stages. In this study, we develop a UME-adaptable 4D hydrogel dressing to sequentially provide an early-vascularized microenvironment and later-antifibrogenic microenvironment for scarless urethral reconstruction. With the combination of dynamic boronic ester crosslinking and covalent photopolymerization, the resultant gelatin methacryloyl phenylboronic acid/cis-diol-crosslinked (GMPD) hydrogels exhibit mussel-mimetic viscoelasticity, satisfactory adhesion, and acid-reinforced stability, which can adapt to harsh UME. In addition, a temporally on-demand regulatory (TOR) technical platform is introduced into GMPD hydrogels to create a time-dependent 4D microenvironment. As a result, physiological urethral recovery is successfully mimicked by means of an early-vascularized microenvironment to promote wound healing by activating the vascular endothelial growth factor (VEGF) signaling pathway, as well as a later-antifibrogenic microenvironment to prevent hypertrophic scar formation by timing transforming growth factor-ß (TGFß) signaling pathway inhibition. Both in vitro molecular mechanisms of the physiological healing process and in vivo scarless urethral reconstruction in a rabbit model are effectively verified, providing a promising alternative for urethral injury treatment.
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Hidrogéis , Procedimentos de Cirurgia Plástica , Animais , Coelhos , Hidrogéis/farmacologia , Fator A de Crescimento do Endotélio Vascular/farmacologia , Cicatrização , BandagensRESUMO
BACKGROUND: There is uncertainty about the optimum sleep duration for risk of different subtypes of stroke and ischaemic heart disease. METHODS: The present analyses involved 409,156 adults in the China Kadoorie Biobank study without a prior history of coronary heart disease or stroke or insomnia symptoms. The mean age of study participants was 52 years and 59% were women. Self-reported sleep duration including daytime napping was recorded using a questionnaire. The adjusted hazard ratios (HRs) for disease outcomes associated with sleep duration were estimated by Cox proportional hazards after adjustment for confounding factors. RESULTS: The overall mean (SD) sleep duration was 7.4 (1.4) hours. The associations of sleep duration with CVD types were U-shaped, with individuals reporting 7-8 h of sleep having the lowest risks. Compared with those who typically slept 7-8 h, individuals with very short sleep duration (≤ 5 h) had adjusted HRs of 1.10 (95% CI 1.04-1.16), 1.07 (1.01-1.13), 1.19 (1.06-1.33) and 1.23 (1.10-1.37) for total stroke, ischaemic stroke (IS), Intracerebral haemorrhage (ICH) and major coronary events (MCE), respectively. Likewise, individuals with very long sleep duration (≥ 10 h) had HRs of 1.12 (1.07-1.17), 1.08 (1.03-1.14), 1.23 (1.12-1.35) and 1.22 (1.10-1.34) for the same diseases, respectively, with little differences by sex and age. The patterns were similar for all-cause mortality. CONCLUSIONS: While abnormal sleep duration (≤ 6 h or ≥ 9 h) was associated with higher risks of CVD, the risks were more extreme for those reporting ≤ 5 or ≥ 10 h, respectively and such individuals should be prioritised for more intensive treatment for CVD prevention.
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Isquemia Encefálica , Doença das Coronárias , Acidente Vascular Cerebral , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Masculino , Acidente Vascular Cerebral/epidemiologia , Duração do Sono , Estudos Prospectivos , Isquemia Encefálica/epidemiologia , População do Leste Asiático , Doença das Coronárias/epidemiologiaRESUMO
Despite numerous studies on tissue-engineered injectable cartilage, it is still difficult to realize stable cartilage formation in preclinical large animal models because of suboptimal biocompatibility, which hinders further application in clinical settings. In this study, we proposed a novel concept of cartilage regeneration units (CRUs) based on hydrogel microcarriers for injectable cartilage regeneration in goats. To achieve this goal, hyaluronic acid (HA) was chosen as the microparticle to integrate gelatin (GT) chemical modification and a freeze-drying technology to create biocompatible and biodegradable HA-GT microcarriers with suitable mechanical strength, uniform particle size, a high swelling ratio, and cell adhesive ability. CRUs were then prepared by seeding goat autologous chondrocytes on the HA-GT microcarriers and culturing in vitro. Compared with traditional injectable cartilage methods, the proposed method forms relatively mature cartilage microtissue in vitro and improves the utilization rate of the culture space to facilitate nutrient exchange, which is necessary for mature and stable cartilage regeneration. Finally, these precultured CRUs were used to successfully regenerate mature cartilage in nude mice and in the nasal dorsum of autologous goats for cartilage filling. This study provides support for the future clinical application of injectable cartilage.
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Cabras , Hidrogéis , Animais , Camundongos , Hidrogéis/farmacologia , Camundongos Nus , Cartilagem , Regeneração , Gelatina/farmacologiaRESUMO
Three-dimensional (3D) bioprinted cartilage-mimicking substitutes for full-thickness articular cartilage defect repair have emerged as alternatives to in situ defect repair models. However, there has been very limited breakthrough in cartilage regeneration based on 3D bioprinting owing to the lack of ideal bioinks with printability, biocompatibility, bioactivity, and suitable physicochemical properties. In contrast to animal-derived natural polymers or acellular matrices, human-derived Wharton's jelly is biocompatible and hypoimmunogenic with an abundant source. Although acellular Wharton's jelly can mimic the chondrogenic microenvironment, it remains challenging to prepare both printable and biologically active bioinks from this material. Here, we firstly prepared methacryloyl-modified acellular Wharton's jelly (AWJMA) using a previously established photo-crosslinking strategy. Subsequently, we combined methacryloyl-modified gelatin with AWJMA to obtain a hybrid hydrogel that exhibited both physicochemical properties and biological activities that were suitable for 3D bioprinting. Moreover, bone marrow mesenchymal stem cell-loaded 3D-bioprinted cartilage-mimicking substitutes had superior advantages for the survival, proliferation, spreading, and chondrogenic differentiation of bone marrow mesenchymal stem cells, which enabled satisfactory repair of a model of full-thickness articular cartilage defect in the rabbit knee joint. The current study provides a novel strategy based on 3D bioprinting of cartilage-mimicking substitutes for full-thickness articular cartilage defect repair.
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Naturally occurring fluorescent proteins (FPs) are the most widely used tools for tracking cellular proteins and sensing cellular events. Here, we chemically evolved the self-labeling SNAP-tag into a palette of SNAP-tag mimics of fluorescent proteins (SmFPs) that possess bright, rapidly inducible fluorescence ranging from cyan to infrared. SmFPs are integral chemical-genetic entities based on the same fluorogenic principle as FPs, i.e., induction of fluorescence of non-emitting molecular rotors by conformational locking. We demonstrate the usefulness of these SmFPs in real-time tracking of protein expression, degradation, binding interactions, trafficking, and assembly, and show that these optimally designed SmFPs outperform FPs like GFP in many important ways. We further show that the fluorescence of circularly permuted SmFPs is sensitive to the conformational changes of their fusion partners, and that these fusion partners can be used for the development of single SmFP-based genetically encoded calcium sensors for live cell imaging.
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Correction for 'Reinforced hydrogel network building by a rapid dual-photo-coupling reaction for 3D printing' by Renjie Zhou et al., Chem. Commun., 2023, 59, 1963-1966, https://doi.org/10.1039/D2CC05677A.
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Background: Whether lifestyle improvement benefits in reducing cardiovascular diseases (CVD) events extend to hypertensive patients and whether these benefits differ between hypertensive and normotensive individuals is unclear. This study aimed to investigate the associations of an overall healthy lifestyle with the subsequent development of CVD among participants with hypertension and normotension. Methods: Using data from the Suzhou subcohort of the China Kadoorie Biobank study of 51,929 participants, this study defined five healthy lifestyle factors as nonsmoking or quitting for reasons other than illness; nonexcessive alcohol intake; relatively higher physical activity level; a relatively healthy diet; and having a standard waist circumference and body mass index. We estimated the associations of these lifestyle factors with CVD, ischemic heart disease (IHD) and ischemic stroke (IS). Results: During a follow-up of 10.1 years, this study documented 6,151 CVD incidence events, 1,304 IHD incidence events, and 2,243 IS incidence events. Compared to those with 0-1 healthy lifestyle factors, HRs for those with 4-5 healthy factors were 0.71 (95% CI: 0.62, 0.81) for CVD, 0.56 (95% CI: 0.42, 0.75) for IHD, and 0.63 (95% CI: 0.51, 0.79) for IS among hypertensive participants. However, we did not observe this association among normotensive participants. Stratified analyses showed that the association between a healthy lifestyle and IHD risk was stronger among younger participants, and the association with IS risk was stronger among hypertensive individuals with lower household incomes. Conclusion: Adherence to a healthy lifestyle pattern is associated with a lower risk of cardiovascular diseases among hypertensive patients, but this benefit is not as pronounced among normotensive patients.
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A facile hydrogel fabrication strategy based on a simultaneous dual-photo-coupling reaction (i.e., photoinduced S-nitrosylation and Schiff base reaction) was reported. This strategy allowed a strengthened three-arm crosslinking network to form in one step and the hydrogels obtained displayed rapid gelation, excellent mechanical strength and biocompatibility for cell encapsulated-3D printing in real time. Our hydrogel fabrication strategy will likely foster advances in biomaterials and the extreme speed and reinforced mechanical strength should significantly benefit 3D printing and related applications.
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Materiais Biocompatíveis , Hidrogéis , Impressão Tridimensional , Engenharia TecidualRESUMO
Tissue engineering is a promising strategy for cartilage defect repair. However, autologous cartilage regeneration is limited by additional trauma to the donor site and a long in vitro culture period. Alternatively, allogenic cartilage regeneration has attracted attention because of the unique advantages of an abundant donor source and immediate supply, but it will cause immune rejection responses (IRRs), especially in immunocompetent large animals. Therefore, a universal technique needs to be established to overcome IRRs for allogenic cartilage regeneration in large animals. In the current study, a hybrid synthetic-natural electrospun thermoplastic polyurethane/gelatin (TPU/GT) semipermeable membrane to explore the feasibility of stable allogenic cartilage regeneration by an immunoisolation strategy is developed. In vitro results demonstrated that the rationally designed electrospun TPU/GT membranes has ideal biocompatibility, semipermeability, and an immunoisolation function. In vivo results further showed that the semipermeable membrane (SPM) efficiently blocked immune cell attack, decreased immune factor production, and cell apoptosis of the regenerated allogenic cartilage. Importantly, TPU/GT-encapsulated cartilage-sheet constructs achieved stable allogeneic cartilage regeneration in a goat model. The current study provides a novel strategy for allogenic cartilage regeneration and supplies a new cartilage donor source to repair various cartilage defects.
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Cartilagem Articular , Cabras , Animais , Cartilagem , Engenharia Tecidual/métodos , Regeneração/fisiologia , Alicerces Teciduais , CondrócitosRESUMO
BACKGROUND: In China, the quantity of physical activity differs from that in Western countries. Substantial uncertainty remains about the relevance of physical activity for cancer subtypes among Chinese adults. OBJECTIVE: This study aimed to investigate the association between total daily physical activity and the incidence of common types of cancer. METHODS: A total of 53,269 participants aged 30-79 years were derived from the Wuzhong subcohort of the China Kadoorie Biobank study during 2004-2008. We included 52,938 cancer-free participants in the final analysis. Incident cancers were identified through linkage with the health insurance system and death registries. Cox proportional hazard models were introduced to assess the associations of total daily physical activity with the incidence of 6 common types of cancer. RESULTS: During a follow-up of 10.1 years, 3,674 cases of cancer were identified, including 794 (21.6%) from stomach cancer, 722 (19.7%) from lung cancer, 458 (12.5%) from colorectal cancer, 338 (9.2%) from liver cancer, 250 (6.8%) from breast cancer, and 231 (6.3%) from oesophageal cancer. Compared to the participants in the lowest quartile of physical activity levels, those in the highest quartile had an 11% lower risk for total cancer incidence (hazard ratio [HR]: 0.89, 95% confidence interval [CI]: 0.81-0.99), 25% lower risk for lung cancer incidence (HR: 0.75, 95% CI: 0.60-0.94), and 26% lower risk for colorectal cancer incidence (HR: 0.74, 95% CI: 0.55-1.00). There were significant interactions of physical activity with sex and smoking on total cancer (both P for interaction < 0.005), showing a lower risk for females and never smokers (HR: 0.92, 95% CI: 0.87-0.98 and HR: 0.93, 95% CI: 0.87-0.98, respectively). CONCLUSIONS: Higher physical activity levels are associated with a reduced risk of total, lung, and colorectal cancer.
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Neoplasias da Mama , Neoplasias Colorretais , Neoplasias Pulmonares , Adulto , Feminino , Humanos , Estudos Prospectivos , Fatores de Risco , População do Leste Asiático , Incidência , China/epidemiologia , Modelos de Riscos Proporcionais , Exercício Físico , Neoplasias da Mama/epidemiologia , Neoplasias Pulmonares/epidemiologia , Neoplasias Colorretais/epidemiologiaRESUMO
The fabrication of biphasic cartilage-bone integrated scaffolds is an attractive alternative for osteochondral repair but has proven to be extremely challenging. Existing three-dimensional (3D) scaffolds are insufficient to accurately biomimic the biphasic cartilage-bone integrated microenvironment. Currently, photo-crosslinkable hydrogels based on tissue-specific decellularized extracellular matrix (dECM) have been considered as an important technique to fabricate biomimetic scaffolds, but so far there has been no breakthrough in the photo-crosslinkable hydrogel scaffolds with biphasic cartilage-bone biomimetic microenvironment. Here, we report a novel strategy for the preparation of biomimetic cartilage-bone integrated scaffolds based on photo-crosslinkable cartilage/bone-derived dECM hydrogels, which are able to reconstruct biphasic cartilage-bone biomimetic microenvironment. The biphasic cartilage-bone integrated scaffolds provided a 3D microenvironment for osteochondral regeneration. The cartilage biomimetic scaffolds, consisting of cartilage-derived dECM hydrogels, efficiently regulated chondrogenesis of bone marrow mesenchymal stem cells (BMSCs). The bone biomimetic scaffolds, composed of cartilage/bone-derived dECM hydrogels, first regulated chondrogenesis of BMSCs, followed by endochondral ossification over time. Taken together, the biphasic cartilage-bone integrated tissue could be successfully reconstructed by subcutaneous culture based on cartilage-bone bilayered structural design. Furthermore, the biphasic cartilage-bone biomimetic scaffolds (cell-free) achieved satisfactory cartilage-bone integrated regeneration in the osteochondral defects of rabbits' knee joints.
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Tissue engineering technology provides a promising approach for large-scale bone reconstruction in cases of extensive chest wall defects. However, previous studies did not consider meticulous scaffold design specific to large-scale rib regeneration in terms of three-dimensional (3D) shape, proper porous structures, enough mechanical strength, and osteogenic microenvironments. Thus, there is an urgent need to develop an appropriate bone biomimetic scaffold (BBS) to address this problem. In this study, a BBS with controllable 3D morphology, appropriate mechanical properties, good biocompatibility and biodegradability, porous structure suitable for cell loading, and a biomimetic osteogenic inorganic salt (OIS) microenvironment was successfully prepared by integrating computer-aided design, 3D-printing, cast-molding, and freeze-drying technologies. The addition of the OIS in the scaffold substantially promoted ectopic bone regeneration in vivo, which might be attributed to the activation of osteogenic and angiogenic signaling pathways as well as upregulated expression of osteogenic genes. More importantly, dual long rib defects could be successfully repaired and medullary cavity recanalized by the rib-shaped mature cortical bone, which might be mediated by the activation of osteoclast signaling pathways. Thus, this paper presents a reliable BBS and proposes a new strategy for the repair of large-scale bone defects.
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Biomimética , Alicerces Teciduais , Regeneração Óssea , Osteogênese , Impressão Tridimensional , Costelas , Aço , Engenharia Tecidual/métodos , Alicerces Teciduais/químicaRESUMO
Functional segmental trachea reconstruction remains a remarkable challenge in the clinic. To date, functional trachea regeneration with alternant cartilage-fibrous tissue-mimetic structure similar to that of the native trachea relying on the three-dimensional (3D) bioprinting technology has seen very limited breakthrough. This fact is mostly due to the lack of tissue-specific bioinks suitable for both cartilage and vascularized fibrous tissue regeneration, as well as the need for firm interfacial integration between stiff and soft tissues. Here, a novel strategy is developed for 3D bioprinting of cartilage-vascularized fibrous tissue-integrated trachea (CVFIT), utilizing photocrosslinkable tissue-specific bioinks. Both cartilage- and fibrous tissue-specific bioinks created by this study provide suitable printability, favorable biocompatibility, and biomimetic microenvironments for chondrogenesis and vascularized fibrogenesis based on the multicomponent synergistic effect through the hybrid photoinitiated polymerization reaction. As such, the tubular analogs are successfully bioprinted and the ring-to-ring alternant structure is tightly integrated by the enhancement of interfacial bonding through the amidation reaction. The results from both the trachea regeneration and the in situ trachea reconstruction demonstrate the satisfactory tissue-specific regeneration along with realization of mechanical and physiological functions. This study thus illustrates the 3D-bioprinted native tissue-like trachea as a promising alternative for clinical trachea reconstruction.
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Bioimpressão , Engenharia Tecidual , Bioimpressão/métodos , Condrogênese , Impressão Tridimensional , Engenharia Tecidual/métodos , Traqueia/cirurgiaRESUMO
Because of the superior characteristics of photocrosslinkable hydrogels suitable for 3D cell-laden bioprinting, tissue regeneration based on photocrosslinkable hydrogels has become an important research topic. However, due to nutrient permeation obstacles caused by the dense networks and static culture conditions, there have been no successful reports on in vitro cartilage regeneration with certain thicknesses based on photocrosslinkable hydrogels. To solve this problem, hydrostatic pressure (HP) provided by the bioreactor was used to regulate the in vitro cartilage regeneration based on hybrid photocrosslinkable (HPC) hydrogel. Chondrocyte laden HPC hydrogels (CHPC) were cultured under 5 MPa HP for 8 weeks and evaluated by various staining and quantitative methods. Results demonstrated that CHPC can maintain the characteristics of HPC hydrogels and is suitable for 3D cell-laden bioprinting. However, HPC hydrogels with concentrations over 3% wt% significantly influenced cell viability and in vitro cartilage regeneration due to nutrient permeation obstacles. Fortunately, HP completely reversed the negative influences of HPC hydrogels at 3% wt%, significantly enhanced cell viability, proliferation, and extracellular matrix (ECM) deposition by improving nutrient transportation and up-regulating the expression of cartilage-specific genes, and successfully regenerated homogeneous cartilage with a thickness over 3 mm. The transcriptome sequencing results demonstrated that HP regulated in vitro cartilage regeneration primarily by inhibiting cell senescence and apoptosis, promoting ECM synthesis, suppressing ECM catabolism, and ECM structure remodeling. Evaluation of in vivo fate indicated that in vitro regenerated cartilage in the HP group further developed after implantation and formed homogeneous and mature cartilage close to the native one, suggesting significant clinical potential. The current study outlines an efficient strategy for in vitro cartilage regeneration based on photocrosslinkable hydrogel scaffolds and its in vivo application.