Perioperative Short-Term Glucocorticoids Do Not Increase Incidence of Complications after Total Joint Arthroplasty in Patients with Rheumatoid Arthritis.

OBJECTIVES: The safety and analgesic efficacy of perioperative glucocorticoids have been established for patients without rheumatoid arthritis. Therefore, our study aims to investigate whether similar benefits can be observed in patients with rheumatoid arthritis undergoing total joint arthroplasty. Specifically, we aim to explore the impact of perioperative glucocorticoid use on postoperative complications, opioid consumption, incidence of hypotension, hyperglycemia, 30-day mortality, and 90-day re-admission in this patient population. METHODS: Approval for the study protocol was obtained from the Medical Research Ethics Committee at Sichuan University, aligning with the principles outlined in the Declaration of Helsinki. We retrospectively analyzed a consecutive series of patients with rheumatoid arthritis who underwent total joint arthroplasty at our medical center between November 2009 and April 2021 and who were not on chronic glucocorticoid therapy before surgery. Those who received glucocorticoids at any time during hospitalization were compared to those who did not in terms of acute complications within 90 days after surgery as well as postoperative rescue opioid consumption, hypotension, and hyperglycemia during hospitalization. The two groups were also compared in terms of overall duration of hospitalization, all-cause mortality within 30 days, and readmission for any reason within 90 days. Continuous data were assessed for significance using the independent-samples t test. Categorical data were assessed using the Pearson chi-squared test. RESULTS: Of the 849 patients included in the analysis, 598 administered perioperative glucocorticoids and 251 did not. Prior to surgery, the two groups did not differ significantly in any clinicodemographic variable that we examined. The incidence of acute postoperative complications (2.3% vs. 4.0%, p = 0.187) and acute postoperative infection (2.0% vs. 2.8%, p = 0.482) was comparable between those who received perioperative glucocorticoids and those who did not, but the former group exhibited a significantly lower incidence of rescue opioid use (17.9% vs. 44.6%, p < 0.001) as well as significantly lower total rescue opioid consumption (4.7 ± 2.1 mg vs. 8.9 ± 4.6 mg, p < 0.001). However, the two groups showed similar incidences of postoperative hypotension, hyperglycemia, 30-day mortality, and 90-day re-admission. CONCLUSION: Perioperative glucocorticoids may reduce the need for rescue opioids after total joint arthroplasty of rheumatoid arthritis patients, without increasing the incidence of acute complications, hypotension or hyperglycemia.

A Composite Hydrogel Functionalized by Borosilicate Bioactive Glasses and VEGF for Critical-Size Bone Regeneration.

Critical-size bone defects pose a formidable challenge in clinical treatment, prompting extensive research efforts to address this problem. In this study, an inorganic-organic multifunctional composite hydrogel denoted as PLG-g-TA/VEGF/Sr-BGNPs is developed, engineered for the synergistic management of bone defects. The composite hydrogel demonstrated the capacity for mineralization, hydroxyapatite formation, and gradual release of essential functional ions and vascular endothelial growth factor (VEGF) and also maintained an alkaline microenvironment. The composite hydrogel promoted the proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs), as indicated by increased expression of osteogenesis-related genes and proteins in vitro. Moreover, the composite hydrogel significantly enhanced the tube-forming capability of human umbilical vein endothelial cells (HUVECs) and effectively inhibited the process of osteoblastic differentiation of nuclear factor kappa-B ligand (RANKL)-induced Raw264.7 cells and osteoclast bone resorption. After the implantation of the composite hydrogel into rat cranial bone defects, the expression of osteogenic and angiogenic biomarkers increased, substantiating its efficacy in promoting bone defect repair in vivo. The commendable attributes of the multifunctional composite hydrogel underscore its pivotal role in expediting hydrogel-associated bone growth and repairing critical bone defects, positioning it as a promising adjuvant therapy candidate for large-segment bone defects.

Socioeconomic disparities in the association of age at first live birth with incident stroke among Chinese parous women: A prospective cohort study.

Background: Stroke has become a significant public health issue in China. Although studies have shown that women's age at first live birth (AFLB) might be associated with incident stroke, there is limited evidence on this relationship among Chinese parous women. Likewise, the nature of this association across urban-rural socioeconomic status (SES) has yet to be explored. In this prospective study, we sought to investigate the associations of women's AFLB with the risk of incident stroke and its subtypes (ischaemic stroke, intracerebral haemorrhage, and subarachnoid haemorrhage) and to explore the differences of these associations as well as the population-level impacts across SES classes. Methods: We used data on 290 932 Chinese parous women from the China Kadoorie Biobank who were recruited in the baseline survey between 2004 and 2008 and followed up until 2015. We used latent class analysis to identify urban-rural SES classes and Cox proportional hazard regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for AFLB's association with incident stroke. We then calculated population attributable fraction (PAF) to demonstrate the population-level impact of later AFLB on stroke. Results: Around 8.9% of parous women developed stroke after AFLB. Compared with women with AFLB <22 years, those with older AFLB had a higher risk of total stroke, with fully adjusted HRs (95% CI) of 1.71 (95% CI = 1.65-1.77) for 22-24 years and 3.37 (95% CI = 3.24-3.51) for ≥25 years. The associations of AFLB with ischaemic stroke were stronger among rural-low-SES participants. We found the highest PAFs of ischaemic stroke (60.1%; 95% CI = 46.2-70.3) associated with later AFLB for urban-high-SES individuals. Conclusions: Older AFLB was associated with higher risks of incident stroke and its subtypes among Chinese parous women, with stronger associations between AFLB and ischaemic stroke among rural-low-SES participants. Targeted medical advice for pregnant women of different ages could have long-term benefits for stroke prevention.

The learning curve of a novel seven-axis robot-assisted total hip arthroplasty system: a randomized controlled trial.

BACGROUND: The aim of this study was to assess the learning curve of a novel seven-axis robot-assisted total hip arthroplasty (RaTHA) system. METHODS: A total of 59 patients who underwent unilateral total hip arthroplasty at our institution from June 2022 to September 2022 were prospectively included in the study. In this randomized controlled clinical trial, robot-assisted THA (RaTHA) and Conventional THA (CoTHA) were performed using cumulative sum (CUSUM) analysis to evaluate the learning curve of the RaTHA system. The demographic data, preopera1tive clinical data, duration of operation, postoperative Harris Hip Score (HHS), postoperative Western Ontario and McMaster Universities Arthritis Index (WOMAC) score, and duration of operation between the learning stage and the proficiency stage of the RaTHA group were compared between the two groups. RESULTS: The average duration of operation of the RaTHA group was increased by 34.73 min compared with the CoTHA group (104.26 ± 19.33 vs. 69.53 ± 18.38 min, p < 0.01). The learning curve of the RaTHA system can be divided into learning stage and proficiency stage, and the former consists of the first 13 cases by CUSUM analysis. In the RaTHA group, the duration of operation decreased by 29.75 min in the proficiency stage compared to the learning stage (121.12 ± 12.84 vs.91.37 ± 12.92, p < 0.01). CONCLUSIONS: This study demonstrated that the surgical team required a learning curve of 13 cases to become proficient using the RaTHA system. The duration of operation, total blood loss, and drainage gradually shortened (decreased) with the learning curve stage, and the differences were statistically significant. TRIAL REGISTRATION: Number: ChiCTR2200061630, Date: 29/06/2022.

The Long-term Efficacy of Total Knee Arthroplasty on End-stage Kashin-Beck Disease of the Knee in Highland Tibetan Areas Patients: A Retrospective Study with 10-Year Follow-up.

OBJECTIVE: Despite the established success of total knee arthroplasty (TKA) with end-stage osteoarthritis, there is a notable scarcity of research on its long-term outcomes in individuals suffering from end-stage Kashin-Beck disease (KBD). This retrospective study aimed to assess the long-term outcomes and effectiveness of clinical function, quality of life, and complications of TKA and end-stage KBD patients in Tibetan highland areas. METHODS: The retrospective cohort included 43 KBD patients, comprising a total of 59 knees, who had undergone TKA at West China Hospital, Sichuan University between 2008 and 2021. Patients were subsequently followed up for a minimum of 3 years, and received rigorous radiological and clinical assessments at 3, 6, and 12 months post surgery, followed by annual examinations thereafter. The evaluation included various efficacy indices, including visual analogue scale (VAS) scores, hospital for special surgery (HSS) scores, functional score for adult Tibetans with Kashin-Beck disease (FSAT-KBD), and radiographic findings. Comparison of indicators within the same group was conducted using one-way repeated-measures analysis of variance or paired sample t-tests, whereas between-group differences were compared using an independent t-test. RESULTS: Throughout the average follow-up duration of 10.8 years, patients experienced a substantial reduction in knee pain and noteworthy functional improvement. The VAS scores decreased significantly from 77.47 ± 4.12 mm before surgery to 10.91 ± 1.97 mm after surgery, indicating considerable alleviation of knee pain. The HSS scores improved markedly, increasing from 44.26 ± 4.95 preoperatively to 91.26 ± 4.37, indicating enhanced joint function. Similarly, the FSAT-KBD exhibited positive progression, increasing from 25.90 ± 3.12 to 36.95 ± 3.54. Importantly, at the last follow-up, none of the patients presented with periprosthetic infection, prosthesis loosening, or periprosthetic fracture. CONCLUSION: At long-term follow-up, compared with patients in the preoperative period, patients in Tibetan highland areas with KBD of the knee who underwent TKA benefited from a significant reduction in pain, improvement in joint function, and satisfactory improvement in quality of life.

Copper-Cystine Biohybrid-Embedded Nanofiber Aerogels Show Antibacterial and Angiogenic Properties.

Copper-cystine-based high aspect ratio structures (CuHARS) possess exceptional physical and chemical properties and exhibit remarkable biodegradability in human physiological conditions. Extensive testing has confirmed the biocompatibility and biodegradability of CuHARS under diverse biological conditions, making them a viable source of essential Cu2+. These ions are vital for catalyzing the production of nitric oxide (NO) from the decomposition of S-nitrosothiols (RSNOs) found in human blood. The ability of CuHARS to act as a Cu2+ donor under specific concentrations has been demonstrated in this study, resulting in the generation of elevated levels of NO. Consequently, this dual function makes CuHARS effective as both a bactericidal agent and a promoter of angiogenesis. In vitro experiments have shown that CuHARS actively promotes the migration and formation of complete lumens by redirecting microvascular endothelial cells. To maximize the benefits of CuHARS, they have been incorporated into biomimetic electrospun poly(ε-caprolactone)/gelatin nanofiber aerogels. Through the regulated release of Cu2+ and NO production, these channeled aerogels not only provide antibacterial support but also promote angiogenesis. Taken together, the inclusion of CuHARS in biomimetic scaffolds could hold great promise in revolutionizing tissue regeneration and wound healing.

DLP Fabrication of Multiple Hierarchical Biomimetic GelMA/SilMA/HAp Scaffolds for Enhancing Bone Regeneration.

Severe bone defects resulting from trauma and diseases remain a persistent clinical challenge. In this study, a hierarchical biomimetic microporous hydrogel composite scaffold was constructed by mimicking the hierarchical structure of bone. Initially, gelatin methacrylamide (GelMA) and methacrylic anhydride silk fibroin (SilMA) were synthesized, and GelMA/SilMA inks with suitable rheological and mechanical properties were prepared. Biomimetic micropores were then generated by using an aqueous two-phase emulsification method. Subsequently, biomimetic microporous GelMA/SilMA was mixed with hydroxyapatite (HAp) to prepare biomimetic microporous GelMA/SilMA/HAp ink. Hierarchical biomimetic microporous GelMA/SilMA/HAp (M-GSH) scaffolds were then fabricated through digital light processing (DLP) 3D printing. Finally, in vitro experiments were conducted to investigate cell adhesion, proliferation, and inward migration as well as osteogenic differentiation and vascular regeneration effects. In vivo experiments indicated that the biomimetic microporous scaffold significantly promoted tissue integration and bone regeneration after 12 weeks of implantation, achieving 42.39% bone volume fraction regeneration. In summary, this hierarchical biomimetic microporous scaffold provides a promising strategy for the repair and treatment of bone defects.

M2 macrophage-derived exosome-functionalized topological scaffolds regulate the foreign body response and the coupling of angio/osteoclasto/osteogenesis.

Designing scaffolds that can regulate the innate immune response and promote vascularized bone regeneration holds promise for bone tissue engineering. Herein, electrospun scaffolds that combined physical and biological cues were fabricated by anchoring reparative M2 macrophage-derived exosomes onto topological pore structured nanofibrous scaffolds. The topological pore structure of the fiber and the immobilization of exosomes increased the nanoscale roughness and hydrophilicity of the fibrous scaffold. In vitro cell experiments showed that exosomes could be internalized by target cells to promote cell migration, tube formation, osteogenic differentiation, and anti-inflammatory macrophage polarization. The activation of fibrosis, angiogenesis, and macrophage was elucidated during the exosome-functionalized fibrous scaffold-mediated foreign body response (FBR) in subcutaneous implantation in mice. The exosome-functionalized nanofibrous scaffolds also enhanced vascularized bone formation in a critical-sized rat cranial bone defect model. Importantly, histological analysis revealed that the biofunctional scaffolds regulated the coupling effect of angiogenesis, osteoclastogenesis, and osteogenesis by stimulating type H vessel formation. This study elaborated on the complex processes within the cell microenvironment niche during fibrous scaffold-mediated FBR and vascularized bone regeneration to guide the design of implants or devices used in orthopedics and maxillofacial surgery. STATEMENT OF SIGNIFICANCE: How to design scaffold materials that can regulate the local immune niche and truly achieve functional vascularized bone regeneration still remain an open question. Here, combining physical and biological cues, we proposed new insight to cell-free and growth factor-free therapy, anchoring reparative M2 macrophage-derived exosomes onto topological pore structured nanofibrous scaffolds. The exosomes functionalized-scaffold system mitigated foreign body response, including excessive fibrosis, tumor-like vascularization, and macrophage activation. Importantly, the biofunctional scaffolds regulated the coupling effect of angiogenesis, osteoclastogenesis, and osteogenesis by stimulating type H vessel formation.

Interpretable feature extraction and dimensionality reduction in ESM2 for protein localization prediction.

As the application of large language models (LLMs) has broadened into the realm of biological predictions, leveraging their capacity for self-supervised learning to create feature representations of amino acid sequences, these models have set a new benchmark in tackling downstream challenges, such as subcellular localization. However, previous studies have primarily focused on either the structural design of models or differing strategies for fine-tuning, largely overlooking investigations into the nature of the features derived from LLMs. In this research, we propose different ESM2 representation extraction strategies, considering both the character type and position within the ESM2 input sequence. Using model dimensionality reduction, predictive analysis and interpretability techniques, we have illuminated potential associations between diverse feature types and specific subcellular localizations. Particularly, the prediction of Mitochondrion and Golgi apparatus prefer segments feature closer to the N-terminal, and phosphorylation site-based features could mirror phosphorylation properties. We also evaluate the prediction performance and interpretability robustness of Random Forest and Deep Neural Networks with varied feature inputs. This work offers novel insights into maximizing LLMs' utility, understanding their mechanisms, and extracting biological domain knowledge. Furthermore, we have made the code, feature extraction API, and all relevant materials available at https://github.com/yujuan-zhang/feature-representation-for-LLMs.

Rapid Volumetric Bioprinting of Decellularized Extracellular Matrix Bioinks.

Decellularized extracellular matrix (dECM)-based hydrogels are widely applied to additive biomanufacturing strategies for relevant applications. The extracellular matrix components and growth factors of dECM play crucial roles in cell adhesion, growth, and differentiation. However, the generally poor mechanical properties and printability have remained as major limitations for dECM-based materials. In this study, heart-derived dECM (h-dECM) and meniscus-derived dECM (Ms-dECM) bioinks in their pristine, unmodified state supplemented with the photoinitiator system of tris(2,2-bipyridyl) dichlororuthenium(II) hexahydrate and sodium persulfate, demonstrate cytocompatibility with volumetric bioprinting processes. This recently developed bioprinting modality illuminates a dynamically evolving light pattern into a rotating volume of the bioink, and thus decouples the requirement of mechanical strengths of bioprinted hydrogel constructs with printability, allowing for the fabrication of sophisticated shapes and architectures with low-concentration dECM materials that set within tens of seconds. As exemplary applications, cardiac tissues are volumetrically bioprinted using the cardiomyocyte-laden h-dECM bioink showing favorable cell proliferation, expansion, spreading, biomarker expressions, and synchronized contractions; whereas the volumetrically bioprinted Ms-dECM meniscus structures embedded with human mesenchymal stem cells present appropriate chondrogenic differentiation outcomes. This study supplies expanded bioink libraries for volumetric bioprinting and broadens utilities of dECM toward tissue engineering and regenerative medicine.

Decoding the "Fingerprint" of Implant Materials: Insights into the Foreign Body Reaction.

Foreign body reaction (FBR) is a prevalent yet often overlooked pathological phenomenon, particularly within the field of biomedical implantation. The presence of FBR poses a heavy burden on both the medical and socioeconomic systems. This review seeks to elucidate the protein "fingerprint" of implant materials, which is generated by the physiochemical properties of the implant materials themselves. In this review, the activity of macrophages, the formation of foreign body giant cells (FBGCs), and the development of fibrosis capsules in the context of FBR are introduced. Additionally, the relationship between various implant materials and FBR is elucidated in detail, as is an overview of the existing approaches and technologies employed to alleviate FBR. Finally, the significance of implant components (metallic materials and non-metallic materials), surface CHEMISTRY (charge and wettability), and physical characteristics (topography, roughness, and stiffness) in establishing the protein "fingerprint" of implant materials is also well documented. In conclusion, this review aims to emphasize the importance of FBR on implant materials and provides the current perspectives and approaches in developing implant materials with anti-FBR properties.

Meeting the Canadian 24-Hour Movement Guidelines and physical-mental comorbidity among Chinese children and adolescents: Prevalence, associations, and the population impacts.

OBJECTIVES: To examine the association between meeting the Canadian 24-Hour Movement Guidelines and physical-mental comorbidity among children and adolescents in a cross-sectional study. METHODS: A total of 21,061 students aged 11-17 years from Zhejiang Province, China was recruited in the study. We examined the coexistence of five specific physical illnesses - hypertension, high myopia, dental caries, scoliosis, and obesity - with mental illness, specifically depressive symptoms. Generalized linear mixed models were performed to assess the association between overall and specific combinations of movement guidelines and physical-mental comorbidity, presented by odds ratio (OR) and 95% confidence interval (CI). Population attributable fraction (PAF) was calculated to estimate the preventable proportion of comorbid cases via meeting all three movement recommendations. RESULTS: Of the included participants, 19.3% had physical-mental comorbidity. There were 3.8% and 17.0% meeting all three and none of the recommendations, respectively. Meeting at least one recommendation, except for moderate-to-vigorous physical activity recommendation only, was associated with a lower risk of physical-mental comorbidity, with ORs (95% CIs) ranging from 0.72 (0.66-0.79) to 0.40 (0.31-0.51). Meeting more recommendations was associated with decreased comorbid risks, and the association was stronger in 4th-6th graders. The association between specific combinations of recommendations and comorbid risks showed differences by gender and grade. Of the comorbid cases, 42.1% were attributed to not adhering to all three recommendations, and the PAFs varied from 27.4% to 55.7% across different genders and grades. CONCLUSION: Adherence to the 24-h movement guidelines was associated with lower risks of physical-mental comorbidity among children and adolescents.

From beasts to bytes: Revolutionizing zoological research with artificial intelligence.

Since the late 2010s, Artificial Intelligence (AI) including machine learning, boosted through deep learning, has boomed as a vital tool to leverage computer vision, natural language processing and speech recognition in revolutionizing zoological research. This review provides an overview of the primary tasks, core models, datasets, and applications of AI in zoological research, including animal classification, resource conservation, behavior, development, genetics and evolution, breeding and health, disease models, and paleontology. Additionally, we explore the challenges and future directions of integrating AI into this field. Based on numerous case studies, this review outlines various avenues for incorporating AI into zoological research and underscores its potential to enhance our understanding of the intricate relationships that exist within the animal kingdom. As we build a bridge between beast and byte realms, this review serves as a resource for envisioning novel AI applications in zoological research that have not yet been explored.

Luteodorsum huanglongense (Gomphaceae, Gomphales), a New Genus and Species of Gomphoid Fungus from the Loess Plateau, Northwest China.

During an investigation of the macrofungal flora in the Huanglong Mountains of the Loess Plateau, northwest China, a unique gomphoid fungus was discovered and collected. After morphological identification and molecular phylogenetic analyses, a new genus named Luteodorsum and its type species, L. huanglongense, were proposed. Phylogenetic analyses were conducted using datasets of nuclear ribosomal DNA 28S large subunit (LSU), mitochondrial (mt) adenosine triphosphatase (ATPase) subunit 6 (atp6), and mt small-subunit rDNA (mtSSU). The results confirmed that L. huanglongense forms an independent clade within Gomphales, with full maximum likelihood bootstrap support (MLBS), maximum parsimony bootstrap support (MPBS), and Bayesian posterior probability (BPP). L. huanglongense is characterized by its sandy-brown, orange-brown, or coffee-brown color; clavate to infundibuliform shape; wrinkled and ridged hymenophore; ellipsoid to obovoid warted basidiospores; cylindrical to clavate flexuous pleurocystidia; and crystal basal mycelium. Overall, this study contributes to the growing body of knowledge on the diversity and evolution of Gomphales and provides valuable insights into the unique fungal flora found in the Huanglong Mountains.

CPEB2 enhances cell growth and angiogenesis by upregulating ARPC5 mRNA stability in multiple myeloma.

BACKGROUND: The process of multiple myeloma (MM) is the result of the combined action of multiple genes. This study aims to explore the role and mechanism of cytoplasmic polyadenylation element binding protein2 (CPEB2) in MM progression. METHODS: The mRNA and protein expression levels of CPEB2 and actin-related protein 2/3 complex subunit 5 (ARPC5) were assessed by quantitative real-time PCR and western blot analysis. Cell function was determined by cell counting kit 8 assay, soft-agar colony formation assay, flow cytometry and tube formation assay. Fluorescent in situ hybridization assay was used to analyze the co-localization of CPEB2 and ARPC5 in MM cells. Actinomycin D treatment and cycloheximide chase assay were performed to assess the stability of ARPC5. The interaction between CPEB2 and ARPC5 was confirmed by RNA immunoprecipitation assay. RESULTS: CPEB2 and ARPC5 mRNA and protein expression levels were upregulated in CD138+ plasma cells from MM patients and cells. CPEB2 downregulation reduced MM cell proliferation, angiogenesis, and increased apoptosis, while its overexpression had an opposite effect. CPEB2 and ARPC5 were co-localized at cell cytoplasm and could positively regulate ARPC5 expression by mediating its mRNA stability. ARPC5 overexpression reversed the suppressive effect of CPEB2 knockdown on MM progression, and it knockdown also abolished CPEB2-promoted MM progression. Besides, CPEB2 silencing also reduced MM tumor growth by decreasing ARPC5 expression. CONCLUSION: Our results indicated that CPEB2 increased ARPC5 expression through promoting its mRNA stability, thereby accelerating MM malignant process.

Liquid-embedded (bio)printing of alginate-free, standalone, ultrafine, and ultrathin-walled cannular structures.

While there has been considerable success in the three-dimensional bioprinting of relatively large standalone filamentous tissues, the fabrication of solid fibers with ultrafine diameters or those cannular featuring ultrathin walls remains a particular challenge. Here, an enabling strategy for (bio)printing of solid and hollow fibers whose size ranges could be facilely adjusted across a broad spectrum, is reported, using an aqueous two-phase embedded (bio)printing approach combined with specially designed cross-linking and extrusion methods. The generation of standalone, alginate-free aqueous architectures using this aqueous two-phase strategy allowed freeform patterning of aqueous bioinks, such as those composed of gelatin methacryloyl, within the immiscible aqueous support bath of poly(ethylene oxide). Our (bio)printing strategy revealed the fabrication of standalone solid or cannular structures with diameters as small as approximately 3 or 40 µm, respectively, and wall thicknesses of hollow conduits down to as thin as <5 µm. With cellular functions also demonstrated, we anticipate the methodology to serve as a platform that may satisfy the needs for the different types of potential biomedical and other applications in the future, especially those pertaining to cannular tissues of ultrasmall diameters and ultrathin walls used toward regenerative medicine and tissue model engineering.

Nanofiber Aerogels with Precision Macrochannels and LL-37-Mimic Peptides Synergistically Promote Diabetic Wound Healing.

Fast healing of diabetic wounds remains a major clinical challenge. Herein, this work reports a strategy to combine nanofiber aerogels containing precision macrochannels and the LL-37-mimic peptide W379 for rapid diabetic wound healing. Nanofiber aerogels consisting of poly(glycolide-co-lactide) (PGLA 90:10)/gelatin and poly-p-dioxanone (PDO)/gelatin short electrospun fiber segments were prepared by partially anisotropic freeze-drying, crosslinking, and sacrificial templating with three-dimensional (3D)-printed meshes, exhibiting nanofibrous architecture and precision micro-/macrochannels. Like human cathelicidin LL-37, W379 peptide at a concentration of 3 µg/mL enhanced the migration and proliferation of keratinocytes and dermal fibroblasts in a cell scratch assay and a proliferation assay. In vivo studies show that nanofiber aerogels with precision macrochannels can greatly promote cell penetration compared to aerogels without macrochannels. Relative to control and aerogels with and without macrochannels, adding W379 peptides to aerogels with precision macrochannels shows the best efficacy in healing diabetic wounds in mice in terms of cell infiltration, neovascularization, and re-epithelialization. The fast re-epithelization could be due to upregulation of phospho-extracellular signal-regulated kinase (p38 MAPK) after treatment with W379. Together, the approach developed in this work could be promising for the treatment of diabetic wounds and other chronic wounds.

Volumetric additive manufacturing of pristine silk-based (bio)inks.

Volumetric additive manufacturing (VAM) enables fast photopolymerization of three-dimensional constructs by illuminating dynamically evolving light patterns in the entire build volume. However, the lack of bioinks suitable for VAM is a critical limitation. This study reports rapid volumetric (bio)printing of pristine, unmodified silk-based (silk sericin (SS) and silk fibroin (SF)) (bio)inks to form sophisticated shapes and architectures. Of interest, combined with post-fabrication processing, the (bio)printed SS constructs reveal properties including reversible as well as repeated shrinkage and expansion, or shape-memory; whereas the (bio)printed SF constructs exhibit tunable mechanical performances ranging from a few hundred Pa to hundreds of MPa. Both types of silk-based (bio)inks are cytocompatible. This work supplies expanded bioink libraries for VAM and provides a path forward for rapid volumetric manufacturing of silk constructs, towards broadened biomedical applications.