Neutrophil extracellular traps-inspired DNA hydrogel for wound hemostatic adjuvant.

Severe traumatic bleeding may lead to extremely high mortality rates, and early intervention to stop bleeding plays as a critical role in saving lives. However, rapid hemostasis in deep non-compressible trauma using a highly water-absorbent hydrogel, combined with strong tissue adhesion and bionic procoagulant mechanism, remains a challenge. In this study, a DNA hydrogel (DNAgel) network composed of natural nucleic acids with rapid water absorption, high swelling and instant tissue adhesion is reported, like a band-aid to physically stop bleeding. The excellent swelling behavior and robust mechanical performance, meanwhile, enable the DNAgel band-aid to fill the defect cavity and exert pressure on the bleeding vessels, thereby achieving compression hemostasis for deep tissue bleeding sites. The neutrophil extracellular traps (NETs)-inspired DNAgel network also acts as an artificial DNA scaffold for erythrocytes to adhere and aggregate, and activates platelets, promoting coagulation cascade in a bionic way. The DNAgel achieves lower blood loss than commercial gelatin sponge (GS) in male rat trauma models. In vivo evaluation in a full-thickness skin incision model also demonstrates the ability of DNAgel for promoting wound healing. Overall, the DNAgel band-aid with great hemostatic capacity is a promising candidate for rapid hemostasis and wound healing.

Anatomy and function of the canalis sinuosus and its injury prevention and treatment strategies in implant surgery. / çª¦ç®¡çš„è§£å‰–ä¸ŽåŠŸèƒ½åŠå ¶åœ¨ç§æ¤æœ¯ä¸­æŸä¼¤çš„é˜²æ²»ç­–ç•¥.

The canalis sinuosus, a canal containing the anterior superior alveolar nerve bundle, originates from the infraorbital canal and extends along the maxillary sinus and nasal cavity edges to the anterior maxilla. It was once regarded as an anatomical variation. However, with the widespread application of cone beam computed tomography (CBCT), the detection rate of canalis sinuosus in the population has increased. The canalis sinuosus exhibits diverse courses, branching into multiple accessory canals and terminating at the nasal floor or the anterior tooth region, with the majority traversing the palatal side of the central incisor. The anterior superior alveolar nerve bundle within the canalis sinuosus not only innervates and nourishes the maxillary anterior teeth, their corresponding soft tissues, and the maxillary sinus mucosa, but also relates to the nasal septum, lateral nasal wall, and parts of the palatal mucosa. To minimize surgical complications, implantologists need to investigate strategies for preventing and treating canalis sinuosus injuries. Preoperatively, implantologists should use CBCT to identify the canalis sinuosus and virtually design implant placement at a distance of more than 2 mm from the canalis sinuosus. Intraoperatively, implantologists should assess bleeding and patient comfort, complemented by precision surgical techniques such as the use of implant surgical guide plates. Postoperatively, CBCT can be employed to examine the relationship between the implant and the canalis sinuosus, and treatment of canalis sinuosus injuries can be tailored based on the patient's symptoms. This review summarizes the detection of canalis sinuosus in the population, its anatomical characteristics, and its physiological functions in the anterior maxilla, and discusses strategies for effectively avoiding canalis sinuosus injuries during implant surgery, thereby enhancing implantologists' awareness and providing references for clinical decision-making.

Oral administration microrobots for drug delivery.

Oral administration is the most simple, noninvasive, convenient treatment. With the increasing demands on the targeted drug delivery, the traditional oral treatment now is facing some challenges: 1) biologics how to implement the oral treatment and ensure the bioavailability is not lower than the subcutaneous injections; 2) How to achieve targeted therapy of some drugs in the gastrointestinal tract? Based on these two issues, drug delivery microrobots have shown great application prospect in oral drug delivery due to their characteristics of flexible locomotion or driven ability. Therefore, this paper summarizes various drug delivery microrobots developed in recent years and divides them into four categories according to different driving modes: magnetic-controlled drug delivery microrobots, anchored drug delivery microrobots, self-propelled drug delivery microrobots and biohybrid drug delivery microrobots. As oral drug delivery microrobots involve disciplines such as materials science, mechanical engineering, medicine, and control systems, this paper begins by introducing the gastrointestinal barriers that oral drug delivery must overcome. Subsequently, it provides an overview of typical materials involved in the design process of oral drug delivery microrobots. To enhance readers' understanding of the working principles and design process of oral drug delivery microrobots, we present a guideline for designing such microrobots. Furthermore, the current development status of various types of oral drug delivery microrobots is reviewed, summarizing their respective advantages and limitations. Finally, considering the significant concerns regarding safety and clinical translation, we discuss the challenges and prospections of clinical translation for various oral drug delivery microrobots presented in this paper, providing corresponding suggestions for addressing some existing challenges.

Scoping review of military veterans involved in the criminal legal system and their health and healthcare: 5-year update and map to the Veterans-Sequential Intercept Model.

BACKGROUND: A previous scoping review of legal-involved veterans' health and healthcare (1947-2017) identified studies and their limitations. Given the influx of literature published recently, this study aimed to update the previous review and map articles to the Veterans-Sequential Intercept Model (V-SIM) - a conceptual model used by key partners, including Veterans Health Administration, veteran advocates, criminal justice practitioners, and local governments to identify intercept points in the criminal legal system where resources and programming can be provided. Developing an updated resource of literature is essential to inform current research, discover gaps, and highlight areas for future research. METHODS: A systematic search of 5 databases identified articles related to legal-involved veterans' health and healthcare published between December 2017 through December 2022. The first and senior authors conducted abstract reviews, full-text reviews, and data extraction of study characteristics. Finally, each article was sorted by the various intercept points from the V-SIM. RESULTS: Of 903 potentially relevant articles, 107 peer-reviewed publications were included in this review, most related to mental health (66/107, 62%) and used an observational quantitative study design (95/107, 89%). Although most articles did not explicitly use the V-SIM to guide data collection, analyses, or interpretation, all could be mapped to this conceptual model. Half of the articles (54/107, 50%) collected data from intercept 5 (Community Corrections and Support Intercept) of the V-SIM. No articles gathered data from intercepts 0 (Community and Emergency Services Intercept), 1 (Law Enforcement Intercept), or 2 (Initial Detention and Court Hearings Intercept). CONCLUSIONS: There were 107 articles published in the last five years compared to 190 articles published in 70 years covered in the last review, illustrating the growing interest in legal-involved veterans. The V-SIM is widely used by front-line providers and clinical leadership, but not by researchers to guide their work. By clearly tying their research to the V-SIM, researchers could generate results to help guide policy and practice at specific intercept points. Despite the large number of publications, research on prevention and early intervention for legal-involved veterans is lacking, indicating areas of great need for future studies.

Citrate Improves Biomimetic Mineralization Induced by Polyelectrolyte-Cation Complexes Using PAsp-Ca&Mg Complexes.

Magnesium ions are highly enriched in early stage of biological mineralization of hard tissues. Paradoxically, hydroxyapatite (HAp) crystallization is inhibited significantly by high concentration of magnesium ions. The mechanism to regulate magnesium-doped biomimetic mineralization of collagen fibrils has never been fully elucidated. Herein, it is revealed that citrate can bioinspire the magnesium-stabilized mineral precursors to generate magnesium-doped biomimetic mineralization as follows: Citrate can enhance the electronegativity of collagen fibrils by its absorption to fibrils via hydrogen bonds. Afterward, electronegative collagen fibrils can attract highly concentrated electropositive polyaspartic acid-Ca&Mg (PAsp-Ca&Mg) complexes followed by phosphate solution via strong electrostatic attraction. Meanwhile, citrate adsorbed in/on fibrils can eliminate mineralization inhibitory effects of magnesium ions by breaking hydration layer surrounding magnesium ions and thus reduce dehydration energy barrier for rapid fulfillment of biomimetic mineralization. The remineralized demineralized dentin with magnesium-doped HAp possesses antibacterial ability, and the mineralization mediums possess excellent biocompatibility via cytotoxicity and oral mucosa irritation tests. This strategy shall shed light on cationic ions-doped biomimetic mineralization with antibacterial ability via modifying collagen fibrils and eliminating mineralization inhibitory effects of some cationic ions, as well as can excite attention to the neglected multiple regulations of small biomolecules, such as citrate, during biomineralization process.

MicroRNA-146a-loaded magnesium silicate nanospheres promote bone regeneration in an inflammatory microenvironment.

Reconstruction of irregular oral-maxillofacial bone defects with an inflammatory microenvironment remains a challenge, as chronic local inflammation can largely impair bone healing. Here, we used magnesium silicate nanospheres (MSNs) to load microRNA-146a-5p (miR-146a) to fabricate a nanobiomaterial, MSN+miR-146a, which showed synergistic promoting effects on the osteogenic differentiation of human dental pulp stem cells (hDPSCs). In addition, miR-146a exhibited an anti-inflammatory effect on mouse bone marrow-derived macrophages (BMMs) under lipopolysaccharide (LPS) stimulation by inhibiting the NF-κB pathway via targeting tumor necrosis factor receptor-associated factor 6 (TRAF6), and MSNs could simultaneously promote M2 polarization of BMMs. MiR-146a was also found to inhibit osteoclast formation. Finally, the dual osteogenic-promoting and immunoregulatory effects of MSN+miR-146a were further validated in a stimulated infected mouse mandibular bone defect model via delivery by a photocuring hydrogel. Collectively, the MSN+miR-146a complex revealed good potential in treating inflammatory irregular oral-maxillofacial bone defects.

Urban-rural disparities in depressive symptoms and related factors among offspring of advanced maternal mothers: A national cross-sectional study in China.

BACKGROUND: Urbanization remains an important factor affecting the mental health of people. Currently, there is insufficient research on depression among the offspring of women who have children at an advanced maternal age (AMA). The objective of this study is to investigate the urban and rural disparities in depressive symptoms among the offspring of AMA and related influencing factors. METHODS: In this study, a total of 1273 offspring born to AMA were selected from the fourth wave of the China Health and Retirement Longitudinal Study (CHARLS) database. The questionnaire used in the study included demographic information and the Center for Epidemiologic Studies Depression Scale (CESD). Chi-square tests and logistic regression analysis were employed to examine the urban-rural differences. RESULTS: The likelihood of developing depressive symptoms of the offspring of AMA in rural areas was 1.633 times higher (AOR = 1.633; 95%CI: 1.211-2.202) compared to their urban counterparts. Several factors including gender, education, marital status, disability, chronic diseases, and sleep duration showed a linkage with depression among rural based offspring of AMA. For the urban offspring of AMA, only disability and sleep duration exhibited a significant association with depressive symptoms. LIMITATIONS: This study cannot establish a causal relationship between depressive symptoms and the influencing factors for the offspring of AMA. Age range and variables of the respondents needs further consideration. CONCLUSIONS: This study has brought to light the elevated risk of depressive symptoms among rural-based offspring of AMA. Thus, emphasizing the urgent need for targeted interventions and measures to address the negative impact.

Reversion of ACP Nanoparticles into Prenucleation Clusters via Surfactant for Promoting Biomimetic Mineralization: A Physicochemical Understanding of Biosurfactant Role in Biomineralization Process.

Amphiphilic biomolecules are abundant in mineralization front of biological hard tissues, which play a vital role in osteogenesis and dental hard tissue formation. Amphiphilic biomolecules function as biosurfactants, however, their biosurfactant role in biomineralization process has never been investigated. This study, for the first time, demonstrates that aggregated amorphous calcium phosphate (ACP) nanoparticles can be reversed into dispersed ultrasmall prenucleation clusters (PNCs) via breakdown and dispersion of the ACP nanoparticles by a surfactant. The reduced surface energy of ACP@TPGS and the electrostatic interaction between calcium ions and the pair electrons on oxygen atoms of C-O-C of D-α-tocopheryl polyethylene glycol succinate (TPGS) provide driving force for breakdown and dispersion of ACP nanoparticles into ultrasmall PNCs which promote in vitro and in vivo biomimetic mineralization. The ACP@TPGS possesses excellent biocompatibility without any irritations to oral mucosa and dental pulp. This study not only introduces surfactant into biomimetic mineralization field, but also excites attention to the neglected biosurfactant role during biomineralization process.

Developing a universal and reliable temporomandibular joint reference system for quantifying morphological and positional changes.

OBJECTIVES: This study aimed to provide a universal and reliable reference system quantifying temporomandibular joint (TMJ) morphological and positional changes. METHODS: Large field-of-view (FOV) cone-beam computed tomography (CBCT) images (20 TMJs) from 10 preorthognathic surgery patients and limited FOV CBCT images (40 TMJs) from 20 splint therapy-treated patients with temporomandibular disorders were collected. TMJ-specific reference system including a TMJ horizontal reference plane (TMJHP) and a local coordinate system (TMJCS) was constructed with landmarks on cranial base. Its application for TMJ measurements and its spatial relationship to common Frankfort horizontal plane (FHP) and maxillofacial coordinate system (MFCS) were evaluated. RESULTS: Five relevant landmarks were selected to optimally construct TMJ-specific reference system. General parallelism between TMJHP and FHP was demonstrated by minimal angular and constant distance deviation (1.714 ±â€…0.811º; 2.925 ±â€…0.817 mm). Additionally, tiny axial orientational deviations (0.181 ±â€…6.805º) suggested TMJCS rivaled MFCS. Moreover, small deviations in orientations and distances (1.232 ±â€…0.609º; 0.310 ±â€…0.202 mm) indicated considerable reliability for TMJCS construction, with intraclass correlation coefficients (ICCs) ranging from 0.999 to 1.000. Lastly, slight discrepancies in translations and rotations revealed high reliability for condylar positional and morphological measurements (ICC, 0.918-0.999). LIMITATIONS: TMJ-specific reference system was merely tested in two representative FOVs. CONCLUSIONS: This study provides a universal and reliable reference system for TMJ assessment that is applicable to both limited and large FOV CBCT. It would improve comparability among diverse studies and enable comprehensive evaluations of TMJ positional and morphological changes during TMJ-related treatment follow-up such as splint therapy and disease progression.

Clinical accuracy of partially guided implant placement in edentulous patients: A computed tomography-based retrospective study.

OBJECTIVES: This retrospective study was intended to evaluate the clinical accuracy of partially guided template in guiding implant placement in edentulous patients. METHODS: A total of 120 implants were placed in 24 patients with at least one completely edentulous arch with a partially guided system. Based on CBCT data, a repeatable method was used to measure linear and angular deviations of implants at 3D level in Mimics medical software. The influence of supporting tissue and implant region on the accuracy was assessed, followed by the evaluation of direction of linear deviations in biologically vital areas. RESULTS: Linear deviations of all implants were 1.91 ± 0.68 mm, 1.47 ± 0.68 mm, and 1.02 ± 0.69 mm at apical, apical lateral, and apical vertical levels. When at the cervical, cervical lateral, and cervical vertical levels, the linear deviations were 1.53 ± 0.65 mm, 0.98 ± 0.53 mm, and 1.01 ± 0.69 mm, respectively. Angular deviation of all implants was 7.14 ± 3.41°. Implants guided by mucosa + tooth-supported templates showed higher linear deviations at apical vertical level (1.21 ± 0.72 mm vs. 0.86 ± 0.63 mm, p < .05) and cervical vertical level (1.18 ± 0.72 mm vs. 0.87 ± 0.63 mm, p < .05) than mucosa-supported templates, and implants in maxilla were found higher angular deviation than mandible (7.89 ± 3.61° vs. 6.29 ± 2.97°, p < .05). CONCLUSIONS: The partially guided template served as clinically viable surgical assistance in implant placement in edentulous patients. When using mucosa + tooth-supported template or placing implants in maxilla, more caution was required, especially in biologically vital areas.

Odontogenic infections in the antibiotic era: approach to diagnosis, management, and prevention.

PURPOSE: The prevalence of odontogenic infections remains one of the highest in the world. If untreated, odontogenic infections can break through the limitation, disseminate to other organs or spaces, and cause high mortality rates. However, it is still difficult to rapidly target limited or disseminated infections in clinical practice. The type of disseminated odontogenic infections and the responsible bacteria have not been described in detail. METHODS: Search databases (e.g., PubMed, MEDLINE, Web of Science, Embase) for reports published from 2018.1 to 2022.9. Use search strategies: ("odontogenic infections" OR "pulpitis" OR "periapical lesions" OR "periodontal diseases") AND ("disseminated infections" OR "complication"). RESULTS: Fourteen different types of disseminated odontogenic infections, most of which are polymicrobial infections, can spread through the body either direct or through hematogenous diffusion. Multiple microbial infections can be more invasive in the transmission of infection. Secondary infections are commonly associated with bacteria like Fusobacterium spp., Streptococcus spp., Peptostreptococcus spp., Prevotella spp., and Staphylococcus spp. Antibiotics with broad-spectrum activity are fundamental as first-line antimicrobial agents based on the microorganisms isolated from disseminated infections. CONCLUSION: This review elaborates on the epidemiology, microorganisms, risk factors, and dissemination routes, and provides evidence-based opinions on the diagnosis, multidisciplinary management, and prevention of odontogenic infections for dentists and clinicians.

Exoskeleton Partial-Coated Stem Cells for Infarcted Myocardium Restoring.

The integration of abiotic materials with live cells has emerged as an exciting strategy for the control of cellular functions. Exoskeletons consisting ofmetal-organic frameworks are generated to produce partial-coated bone marrow stem cells (BMSCs) to overcome low cell survival leading to disappointing effects for cell-based cardiac therapy. Partially coated exoskeletons can promote the survival of suspended BMSCs by integrating the support of exoskeletons and unimpaired cellular properties. In addition, partial exoskeletons exhibit protective effects against detrimental environmental conditions, including reactive oxygen species, pH changes, and osmotic pressure. The partial-coated cells exhibit increased intercellular adhesion forces to aggregate and adhere, promoting cell survival and preventing cell escape during cell therapy. The exoskeletons interact with cell surface receptors integrin α5ß1, leading to augmented biological functions with profitable gene expression alteration, such as Vegfa, Cxcl12, and Adm. The partial-coated BMSCs display enhanced cell retention in infarcted myocardium through non-invasive intravenous injections. The repair of myocardial infarction has been achieved with improved cardiac function, myocardial angiogenesis, proliferation, and inhibition of cell apoptosis. This discovery advances the elucidation of potential molecular and cellular mechanisms for cell-exoskeleton interactions and benefits the rational design and manufacture of next-generation nanobiohybrids.

Influence of edentulism on the structure and function of temporomandibular joint.

Background: With the acceleration of the aging process of the population, the number of edentulous patients continuously increased. Edentulism induces the loss of occlusal relationship and cause adverse effects on the stomatognathic system. Temporomandibular joint (TMJ), as a significant component of this system, may also be affected by edentulism in the process of supporting mandibular movement. Purpose: Provide a comprehensive review of the structure and function of TMJ in the edentulous population, as well as the prevalence of temporomandibular joint disorder (TMD) in edentulous group. Study selection: An electronic search was conducted on articles prior to December 2022 to filter all papers relevant to the structure and function of TMJ in edentulous population. The internet databases (PubMed, Cochrane Library, Embase) were searched using various combinations of keywords for "edentulism" or "edentulous" and "TMJ" or "TMD". Results: Firstly, 522 articles were selected from the internet database, and finally, a total of 44 articles met the inclusion and exclusion criteria. The research content of these articles mainly focuses on the structure and function of TMJ in edentulous patients, as well as the clinical signs and symptoms of TMD. Conclusions: Edentulous arch induces the loss of occlusal relationship, which may lead to degenerative changes of TMJ components consisting of changes in morphology and bone mass density of condyle, articular fossa, and articular eminence. In addition, the condyle could be shifted backward and upward, and displacement of the articular disc may occur after dentition loss. And the condyle and the articular disc may be guided back to the normal position after effective prosthodontic treatment. But the conclusions of the study on the function of TMJ and the prevalence of TMD in edentulous people are inconsistent. The condition of TMJ, especially the position of condyle-fossa and the symptoms and signs of TMD should not be ignored. If necessary, radiographic examinations should be performed.

Multifocal epithelial hyperplasia confined to the interdental papilla of an adult Chinese man: a rare case report and literature review.

BACKGROUND: Multifocal epithelial hyperplasia (MEH), or focal epithelial hypertension (FEH), or Heck's disease, is an uncommon, benign oral mucosal disease associated with human papillomavirus infection. It is mostly observed in indigenous populations of the world, and has been rarely reported in China. However, previous research suggested there might be a greater prevalence of MEH in the Chinese population. While predominantly involves the lips, buccal mucosa and tongue, MEH was occasionally reported to affect the hard palate and gingiva as well. CASE PRESENTATION: This paper reports a case of extensive MEH lesions that confined to the interdental papilla of a Chinese male without detection of HPV, and summarizes the published gingiva-involved MEH reports from 1966 until present. The lesions were excised with an Er: YAG laser after scaling and root planning, no recurrence was observed after 6-month follow-up. CONCLUSIONS: The present report illustrates the need for clinicians to be aware of rare presentations of MEH to facilitate a prompt diagnosis and proper management. More reports are encouraged to determine a correct prevalence rate of MEH in China.

Public sense of dental implants on social media: A cross-sectional study based on text analysis of comments.

OBJECTIVES: To investigate the most discussed topics and possible new interests in dental implants among the public, as well as the public sentiments toward dental implants through topic and sentiment analysis of online comments. METHODS: Comments of the top 100 most viewed dental implant-related YouTube videos were studied. The comments were analyzed by topic analysis (LDA topic model, Word co-occurrence analysis) and sentiment analysis. The basic information of videos was collected and classified. Video quality was evaluated by GQS criteria and 9-point usefulness scoring system. Statistical analyses were performed using Kruskal-Wallis test, Mann-Whitney U-tests, and Spearman correlation analysis. RESULTS: 74 videos with 61,618 comments were considered eligible in this study. Most videos targeted the public with high viewing and comments, but the theme was single and the quality was low. From topic analysis, the most discussed topics in the comments were procedure, cost, feelings associated with prognosis, and expectations. Multidisciplinary approaches in implant dentistry were frequently discussed. From sentiment analysis, the public mainly expressed positive sentiment through comments. In detail, the public had positive feelings about aesthetics and health, negative feelings about pain, and neutral feelings about cost. CONCLUSION: The hot topics of public concern were procedure, cost, feelings associated with prognosis, and expectations. Intriguingly, multidisciplinary approaches in implant dentistry have emerged as a new hot subtopic within the topic "procedure". Based on the sentiment analysis of the comments, the general sentiment expressed by the public toward dental implants was predominantly positive. CLINICAL SIGNIFICANCE: Text mining can extract data from social media to explore public interest in dentistry. Clinicians should convey reasonable expectations and understanding about dental implants, especially addressing the most public-concerned topics (procedure, cost, feelings, and expectations), and provide patients with well-grounded multidisciplinary treatment plans to meet the growing public demand.

Adjacent tooth migration after maxillary first molar loss in patients with sinus augmentation: A retrospective research.

PURPOSE: The objectives of this study are to: (1) investigate the extent of antagonistic and distal neighboring tooth migration in the maxillary posterior single tooth-missing site during the healing period of bone augmentation and implant surgery; (2) identify factors associated with tooth migration. MATERIALS AND METHODS: One hundred and forty-three cases that lost the maxillary first molar were included, and their CBCT data during the edentulous period were obtained. Dentition models were reconstructed from CBCT, and superimpositions were performed, followed by measuring migration distances and calculating migration rates of antagonistic and distal neighboring teeth. Factors were analyzed using multivariate generalized estimating equations (GEE). RESULTS: The mean migration distances were 208 ± 137 µm and 403 ± 605 µm for antagonistic teeth and distal teeth, and the mean migration rates were 26.8 ± 21.2 µm/month and 48.5 ± 76.7 µm/month, respectively. One hundred and nineteen out of 143 distal neighboring teeth migrated toward the edentulous site, and all antagonistic teeth migrated occlusally. Occlusal contact loss and chronic apical periodontitis both significantly accelerated antagonistic tooth migration (p < 0.05), the latter also accelerated distal tooth migration (p < 0.05). Besides, the displacement of the distal teeth was somewhat accelerated by the impacted adjacent third molar and root protrusion into the sinus. CONCLUSIONS: The neighboring teeth tend to migrate toward the edentulous gap in the maxillary posterior region. Occlusal contact loss and chronic apical periodontitis are two significant risk factors for accelerating antagonistic tooth migration, and for distal teeth, chronic apical periodontitis is the risk factor. The impacted adjacent third molar and root protrusion into the sinus are also potential risk factors for accelerating the migration of the maxillary distal tooth. Thus, to prevent maxillary edentulous gap reduction, the factors mentioned above should be taken into consideration when planning treatment flow.

Injectable rBMSCs-laden hydrogel microspheres loaded with naringin for osteomyelitis treatment.

Osteomyelitis, caused by purulent bacteria invading bone tissue, often occurs in long bones and seriously affects the physical and mental health and working ability of patients; it can even endanger life. However, due to bone cavity structure, osteomyelitis tends to occur inside the bone and thus lacks an effective treatment; anti-inflammatory treatment and repair of bone defects are necessary. Here, we developed injectable hydrogel microspheres loaded with naringin and bone marrow mesenchymal stem cells, which have anti-inflammatory and osteogenic properties. These homogeneous microspheres, ranging from 200 to 1000µm, can be rapidly fabricated using an electro-assisted bio-fabrication method. Interestingly, it was found that microspheres with relatively small diameters (200µm) were more conducive to the initial cell attachment, growth, spread, and later osteogenic differentiation. The developed microspheres can effectively treat tibial osteomyelitis in rats within six weeks, proving their prospects for clinical application.

Co-occurring Medical Multimorbidity, Mental Illness, and Substance Use Disorders Among Older Criminal Legal System-Involved Veterans.

BACKGROUND: Older veterans involved in the criminal legal system (CLS) may have patterns of multimorbidity that place them at risk for poor health outcomes. OBJECTIVES: To estimate the prevalence of medical multimorbidity (≥2 chronic medical diseases), substance use disorders (SUDs), and mental illness among CLS-involved veterans aged 50 and older. RESEARCH DESIGN: Using Veterans Health Administration health records, we estimated the prevalence of mental illness, SUD, medical multimorbidity, and the co-occurrence of these conditions among veterans by CLS involvement as indicated by Veterans Justice Programs encounters. Multivariable logistic regression models assessed the association between CLS involvement, the odds for each condition, and the co-occurrence of conditions. SUBJECTS: Veterans aged 50 and older who received services at Veterans Health Administration facilities in 2019 (n=4,669,447). METHODS: Mental illness, SUD, medical multimorbidity. RESULTS: An estimated 0.5% (n=24,973) of veterans aged 50 and older had CLS involvement. For individual conditions, veterans with CLS involvement had a lower prevalence of medical multimorbidity compared with veterans without but had a higher prevalence of all mental illnesses and SUDs. After adjusting for demographic factors, CLS involvement remained associated with concurrent mental illness and SUD (adjusted odds ratio [aOR] 5.52, 95% CI=5.35-5.69), SUD and medical multimorbidity (aOR=2.09, 95% CI=2.04-2.15), mental illness and medical multimorbidity (aOR=1.04, 95% CI=1.01-1.06), and having all 3 simultaneously (aOR=2.42, 95% CI=2.35-2.49). CONCLUSIONS: Older veterans involved in the CLS are at high risk for co-occurring mental illness, SUDs, and medical multimorbidity, all of which require appropriate care and treatment. Integrated care rather than disease-specific care is imperative for this population.

4D Printing of Personalized-Tunable Biomimetic Periosteum with Anisotropic Microstructure for Accelerated Vascularization and Bone Healing.

An ideal biomimetic periosteum is expected to wrap various bone surfaces to orchestrate an optimal microenvironment for bone regeneration, including facilitating local vascularization, recruiting osteoblasts, and mineralizing the extracellular matrix (ECM). To mimic the role of the natural periosteum in promoting bone repair, a 4D printing technique to inlay aligned cell sheets on shape-shifting hydrogel is used, containing biophysical signals and spatially adjustable physical properties, for the first time. The outer hydrogel layer endows the biomimetic periosteum with the ability to digitally coordinate its 3D geometry to match the specific macroscopic bone shape to maintain a bone healing microenvironment. The inner aligned human mesenchymal stem cells (hMSCs) layer not only promotes the migration and angiogenesis of co-cultured cells but also exhibits excellent osteogenic differentiation properties. In vivo experiments show that apart from morphing preset shapes as physical barriers, the aligned biomimetic periosteum can actively facilitate local angiogenesis and early-stage osteogenesis. Altogether, this present work provides a novel route to construct a personalized biomimetic periosteum with anisotropic microstructure by introducing a tunable shape to maintain the bone reconstruction microenvironment and this strategy can be extended to repair sophisticated bone defects.

DLP printed hDPSC-loaded GelMA microsphere regenerates dental pulp and repairs spinal cord.

Dental pulp regeneration is ideal for irreversible pulp or periapical lesions, and in situ stem cell therapy is one of the most effective therapies for pulp regeneration. In this study, we provided an atlas of the non-cultured and monolayer cultured dental pulp cells with single-cell RNA sequencing and analysis. Monolayer cultured dental pulp cells cluster more closely together than non-cultured dental pulp cells, suggesting a lower heterogeneous population with relatively consistent clusters and similar cellular composition. We successfully fabricated hDPSC-loaded microspheres by layer-by-layer photocuring with a digital light processing (DLP) printer. These hDPSC-loaded microspheres have improved stemness and higher multi-directional differentiation potential, including angiogenic, neurogenic, and odontogenic differentiation. The hDPSC-loaded microspheres could promote spinal cord regeneration in rat spinal cord injury models. Moreover, in heterotopic implantation tests on nude mice, CD31, MAP2, and DSPP immunofluorescence signals were observed, implying the formation of vascular, neural, and odontogenetic tissues. In situ experiments in minipigs demonstrated highly vascularized dental pulp and uniformly arranged odontoblast-like cells in root canals of incisors. In short, hDPSC-loaded microspheres can promote full-length dental pulp regeneration at the root canals' coronal, middle, and apical sections, particularly for blood vessels and nerve formation, which is a promising therapeutic strategy for necrotic pulp.