Nevin Manimala

Physiother Theory Pract. 2025 Mar;41(3):664-681. doi: 10.1080/09593985.2024.2346729. Epub 2024 Apr 26.

ABSTRACT

BACKGROUND: Primary motor cortex (M1) organization and quadriceps femoris excitability may change after anterior cruciate ligament injury (ACLi) and anterior cruciate ligament reconstruction (ACLr), as demonstrated by transcranial magnetic stimulation (TMS) studies.

OBJECTIVE: To systematically review studies evaluating changes in quadriceps femoris corticospinal and intracortical excitability in subjects with ACLi and ACLr.

METHODS: Database searches were conducted in PubMed, Embase, Scopus, and ScienceDirect, with the last search performed on November 23, 2023. Newcastle-Ottawa Scale and a specific checklist for evaluating descriptions in studies using TMS assessment were used. Continuous variables were expressed as mean and standard deviation and represented by the estimated difference from the mean and 95% confidence interval (CI). Heterogeneity was assessed by Chi² and I² and the level of statistical significance was 5%.

RESULTS: Fourteen studies, comprising 381 individuals, using TMS were identified. Meta-analysis results showed significantly higher motor threshold (MT) in ACLi/ACLr individuals compared to healthy controls (p < .01, mean difference 6.72). Additionally, MTs were significantly higher on the uninjured side compared to healthy controls (p < .0001, mean difference 3.82). Motor-evoked potentials (MEP) amplitude was significantly higher on the uninjured side compared to the injured side (p < .00001, mean difference 0.01). Short-interval intracortical inhibition (SICI) amplitude was significantly lesser on the injured limb compared to the uninjured side (p < .00001, mean difference 0.50).

CONCLUSION: Quadriceps MT and SICI are altered in ACLi and ACLr populations, and minor alterations were identified in MEP, demonstrating brain changes related to anterior cruciate ligament injury and/or reconstruction.

PMID:39992686 | DOI:10.1080/09593985.2024.2346729

JAMA Intern Med. 2025 Feb 24. doi: 10.1001/jamainternmed.2024.8354. Online ahead of print.

ABSTRACT

IMPORTANCE: Low-value care is a persistent problem with direct and cascading harms. Telemedicine is now commonly used and may reduce low-value testing by introducing barriers to completing tests at a given visit or expand opportunities for low-value testing by contributing to higher visit volumes.

OBJECTIVE: To quantify the association between telemedicine adoption and low-value testing among fee-for-service Medicare beneficiaries.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study using 100% fee-for-service Medicare claims data, US health systems were divided into quartiles based on 2020 telemedicine adoption. Beneficiary-level linear regression in difference-in-differences (DiD) analyses was used to compare beneficiaries who were continuously enrolled from 2019 through 2022 and were attributed before telemedicine adoption (2019) to high telemedicine-adopting (top quartile) vs low telemedicine-adopting (bottom quartile) health systems on low-value test and visit outcomes in 2022 vs 2019. Data were analyzed from October 2023 to December 2024.

EXPOSURE: Health system telemedicine adoption.

MAIN OUTCOMES AND MEASURES: Receipt of, and spending on, 20 low-value screening, preoperative, chronic condition management, and acute diagnostic tests, as well as total visits (in person and virtual).

RESULTS: The sample included 1 382 033 beneficiaries who were attributed to high-telemedicine systems (mean [SD] age, 71.6 [10.5] years; 58.8% female) and 999 051 beneficiaries who were attributed to low-telemedicine systems (mean [SD] age, 71.8 [10.0] years; 57.0% female). From 2019 to 2022, those in high-telemedicine systems had a small differential rise in visits (DiD visits per beneficiary, 0.12; 95% CI, 0.03 to 0.21) and differential decreases in use of 7 of 20 low-value tests: cervical cancer screening (DiD, -0.45 percentage points [pp]; 95% CI, -0.72 to -0.17 pp), screening electrocardiograms (DiD, -1.30 pp; 95% CI, -1.96 to -0.65 pp), screening metabolic panels (DiD, -1.84 pp; 95% CI, -2.87 to -0.80 pp), preoperative complete blood cell counts (DiD, -0.64 pp; 95% CI, -1.06 to -0.22 pp), preoperative metabolic panels (DiD, -1.35 pp; -1.91 to -0.80 pp), total or free T3 (triiodothyronine) level testing for hypothyroidism (DiD, -0.90 pp; 95% CI, -1.38 to -0.41 pp), and imaging for uncomplicated low back pain (DiD, -1.66 pp; 95% CI, -2.35 to -0.98 pp). There were no statistically significant differences in other tests. Those in high-telemedicine systems saw statistically significant differential decreases in spending on visits per beneficiary (-$47.87; 95% CI, -$86.85 to -$8.88) and on 2 of 20 low-value tests, but no differences in low-value spending overall.

CONCLUSIONS AND RELEVANCE: In this cohort study, telemedicine adoption was associated with modestly lower use of 7 of 20 examined low-value tests (most point-of-care) and no changes in use of other low-value tests, despite a small rise in total visits that might offer more testing opportunities. Results suggest possible benefits of telemedicine and mitigate concerns about telemedicine contributing to increased spending.

PMID:39992684 | DOI:10.1001/jamainternmed.2024.8354

JAMA Pediatr. 2025 Feb 24. doi: 10.1001/jamapediatrics.2024.6613. Online ahead of print.

ABSTRACT

IMPORTANCE: Hypothermia begun less than 6 hours after birth reduces death or disability in infants with encephalopathy due to hypoxia-ischemia at 36 or more weeks’ gestation. Trials of hypothermia for infants younger than 36 weeks’ gestation are lacking.

OBJECTIVE: To assess the probability that hypothermia at less than 6 hours after birth decreases death or disability in infants 33 to 35 weeks’ gestation with moderate or severe hypoxic-ischemic encephalopathy.

DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was conducted between July 2015 and December 2022 for infants 33 to 35 weeks’ gestation with moderate or severe hypoxic-ischemic encephalopathy at less than 6 hours after birth. Bayesian and intention-to-treat analyses were prespecified. The setting included 19 US Neonatal Research Network centers. Data were analyzed from March 2023 to November 2024.

INTERVENTIONS: Infants received unblinded targeted esophageal temperature management. Infants with hypothermia were maintained at 33.5 °C (acceptable 33-34 °C) for 72 hours and then rewarmed. Infants with normothermia were to be maintained at 37 °C (acceptable 36.5-37.3 °C).

MAIN OUTCOMES AND MEASURES: Composite of death or disability (moderate or severe) at 18 to 22 months’ corrected age adjusted for level of encephalopathy and center.

RESULTS: A total of 168 infants with hypothermia and normothermia were preterm (mean [SD] age, 34.0 [0.8] weeks’ gestation and 34.1 [0.8] weeks’ gestation, respectively), while 46 of 88 (52%) and 45 of 80 (56%) were male, respectively. Randomization occurred at mean (SD) 4.5 (1.2) hours and 4.5 (1.3) hours for the groups with hypothermia and normothermia, respectively. The primary outcome occurred in 29 of 83 infants (35%) with hypothermia and 20 of 69 infants (29%) with normothermia (adjusted relative risk [hypothermic/normothermic], 1.11; 95% credibility interval, 0.74-2.00), and death occurred in 18 of 88 infants (20%) with hypothermia and 9 of 78 infants (12%) with normothermia (adjusted relative risk, 1.38; 95% credibility interval, 0.79-2.85). Bayesian analysis with neutral prior indicated 74% probability of increased death or disability and 87% probability of increased death with hypothermia.

CONCLUSIONS AND RELEVANCE: Among infants 33 to 35 weeks’ gestation with hypoxic-ischemic encephalopathy, hypothermia at less than 6 hours’ age did not reduce death or disability at 18 to 22 months’ corrected age.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01793129.

PMID:39992674 | DOI:10.1001/jamapediatrics.2024.6613

JAMA Netw Open. 2025 Feb 3;8(2):e2459672. doi: 10.1001/jamanetworkopen.2024.59672.

ABSTRACT

IMPORTANCE: An estimated 1% to 3% of children with SARS-CoV-2 infection will develop post-COVID-19 condition (PCC).

OBJECTIVE: To evaluate the odds of PCC among children with COVID-19 vaccination prior to SARS-CoV-2 infection compared with odds among unvaccinated children.

DESIGN, SETTING, AND PARTICIPANTS: In this case-control study, children were enrolled in a multisite longitudinal pediatric cohort from July 27, 2021, to September 1, 2022, and followed up through May 2023. Analysis used a case (PCC reported)-control (no PCC reported) design and included children aged 5 to 17 years whose first real time-polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infection occurred during the study period, who were COVID-19 vaccine age-eligible at the time of infection, and who completed a PCC survey at least 60 days after infection. From December 1, 2022, to May 31, 2023, children had weekly SARS-CoV-2 testing and were surveyed regarding PCC (≥1 new or ongoing symptom lasting ≥1 month after infection).

EXPOSURES: COVID-19 mRNA vaccination status at time of infection was the exposure of interest; participants were categorized as vaccinated (≥2-dose series completed ≥14 days before infection) or unvaccinated. Vaccination status was verified through vaccination cards or vaccine registry and/or medical records when available.

MAIN OUTCOME AND MEASURES: Main outcomes were estimates of the odds of PCC symptoms. Multivariate logistic regression was performed to estimate the odds of PCC among vaccinated children compared with odds of PCC among unvaccinated children.

RESULTS: A total of 622 participants were included, with 28 (5%) case participants and 594 (95%) control participants. Median (IQR) age was 10.0 (7.0-11.9) years for case participants and 10.3 (7.8-12.7) years for control participants (P = .37). Approximately half of both groups reported female sex (13 case participants [46%] and 287 control participants [48%]). Overall, 57% of case participants (16 children) and 77% of control participants (458 children) were vaccinated (P = .05). After adjusting for demographic characteristics, number of acute COVID-19 symptoms, and baseline health, COVID-19 vaccination was associated with decreased odds of 1 or more PCC symptom (adjusted odds ratio [aOR], 0.43; 95% CI, 0.19-0.98) and 2 or more PCC symptoms (aOR, 0.27; 95% CI, 0.10-0.69).

CONCLUSIONS AND RELEVANCE: In this study, mRNA COVID-19 vaccination was associated with reduced odds of PCC in children. The aORs correspond to an estimated 57% and 73% reduced likelihood of 1 or more and 2 or more PCC symptoms, respectively, among vaccinated vs unvaccinated children. These findings suggest benefits of COVID-19 vaccination beyond those associated with protection against acute COVID-19 and may encourage increased pediatric uptake.

PMID:39992656 | DOI:10.1001/jamanetworkopen.2024.59672

JAMA Netw Open. 2025 Feb 3;8(2):e2461321. doi: 10.1001/jamanetworkopen.2024.61321.

ABSTRACT

IMPORTANCE: Rates of suicide ideation, severe depression, and acute psychosis have surged, paralleling an increase in emergency department visits for psychiatric emergencies. Mobile crisis services can play an important role in delivering timely, community-based interventions.

OBJECTIVE: To assess the national availability of mobile crisis services in mental health treatment facilities and to identify key facility, geographic, and state-level factors associated with the availability of these services.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed data from the 2022 National Substance Use and Mental Health Services Survey, which included 9036 mental health treatment facilities in the US. Facility zip codes were linked to the Agency for Healthcare Research and Quality’s Social Determinants of Health database to assess area-level factors. The study population included facilities that reported whether they offered mobile crisis services. Data were analyzed from August to September 2024.

MAIN OUTCOMES AND MEASURES: The primary outcome was the availability of mobile crisis services at mental health treatment facilities, as reported by facility directors. Key independent variables included facility characteristics, local area factors, and state Medicaid policies. Logistic regression models were used to examine the associations between these factors and the availability of mobile crisis services.

RESULTS: Of 9036 facilities, 1882 (20.8%) reported offering mobile crisis services. Facilities providing integrated dual diagnosis services (marginal effect, 3.44 [95% CI, 1.41-5.53] percentage points), suicide prevention services (marginal effect, 6.74 [95% CI, 4.29-9.20] percentage points), and assertive community treatment (marginal effect, 11.26 [95% CI, 9.02-13.51] percentage points) were significantly more likely to offer mobile health crisis services. Facilities in areas with lower percentages of residents with only a high school education were also more likely to offer mobile crisis services (marginal effect, 1.33 [95% CI, 0.15-2.51] percentage points).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of US mental health facilities, facilities with integrated services and located in areas with certain geographic characteristics were more likely to offer mobile crisis services. Addressing gaps in service availability is essential to improving access to crisis care.

PMID:39992654 | DOI:10.1001/jamanetworkopen.2024.61321

JAMA Netw Open. 2025 Feb 3;8(2):e2461334. doi: 10.1001/jamanetworkopen.2024.61334.

ABSTRACT

IMPORTANCE: Inflammation impacts cancer risk and tumor biological processes, yet studies linking it to social and environmental risk factors are lacking.

OBJECTIVE: To investigate the association of neighborhood deprivation and air pollution with breast adipose inflammation as well as the association between crown-like structures of the breast (CLS-B) and DNA methylation in Black and White women.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed women with and without breast cancer participating in the National Cancer Institute-Maryland Breast Cancer Study, most of whom were recruited between January 1, 1993, and December 1, 2003, from the University of Maryland Medical Center and surrounding hospitals in the Baltimore, Maryland, area. A small subset of the sample was recruited between March 27, 2012, and November 27, 2017. Noncancerous breast tissue was collected from women who underwent reduction mammoplasty or breast cancer surgery. Statistical analyses were conducted between May and August 2024.

EXPOSURES: Two socioenvironmental exposures were examined: air pollution (specifically, fine particulate matter less than 2.5 μm in diameter [PM2.5]) and neighborhood deprivation (measured with Neighborhood Deprivation Index [NDI]). Participant geocodes were linked to 2000 US Census data to calculate PM2.5 concentrations (total mass [μg/m3]) and NDI.

MAIN OUTCOMES AND MEASURES: Breast tissues underwent immunohistochemical staining for pan-macrophage marker CD68 to detect 2 outcomes: CLS-B and adipose-associated macrophages. CLS-B and adipose-related macrophages were assessed by pathologists using artificial intelligence-assisted and manual approaches. Covariate-adjusted logistic regression models were used to ascertain associations between PM2.5 and NDI (exposures) and presence or absence of CLS-B (outcome); CD68-positive adipose macrophages were modeled as a dichotomous high or low variable. Covariate-adjusted linear regression was used to identify associations between CLS-B (exposure) and DNA methylation (outcome).

RESULTS: The cohort included 205 participants (127 Black [62.0%], 78 White [38.0%] women; mean [SD] age, 48.7 [13.3] years). Women with vs without CLS-B had higher median (IQR) body mass index (calculated as weight in kilograms divided by height in meters squared; 35.5 [30.5-40.9] vs 31.8 [26.6-36.4]; P = .02). Higher levels of PM2.5 (odds ratio [OR], 2.32; 95% CI, 1.12-4.78; P = .02) and NDI (OR, 1.21; 95% CI, 1.02-1.43; P = .03) were associated with presence of CLS-B overall; findings were still significant among Black women (PM2.5: OR, 2.64 [95% CI, 1.10-6.33], P = .03; NDI: OR, 1.22 [95% CI, 1.01-1.48], P = .04) but were not statistically significant among White women (PM2.5: OR, 1.65 [95% CI, 0.45-5.99], P = .45; NDI: OR, 1.19 [95% CI, 0.83-1.70], P = .35). Higher PM2.5 concentration was associated with increased macrophage infiltration (OR, 2.11; 95% CI, 1.24-3.60; P = .006), with similar outcomes by race. The top 2 significant differentially methylated CpG sites by CLS-B status were SAR1B (β = 0.01; 95% CI, 0.01-0.02; P < .001) and IL2RB (β = -0.04; 95% CI, -0.05 to -0.02; P < .001). Significant interaction was observed between CLS-B status and race for IL2RB methylation levels (β = -0.03; 95% CI, -0.04 to -0.01; P for interaction <.001).

CONCLUSIONS AND RELEVANCE: This cross-sectional study uncovered an association between neighborhood-level social and environmental risk factors and breast tissue inflammation. The findings help inform efforts to reduce racial and socioeconomic disparities in breast cancer and improve health equity for socially vulnerable populations.

PMID:39992653 | DOI:10.1001/jamanetworkopen.2024.61334

JAMA Netw Open. 2025 Feb 3;8(2):e2461409. doi: 10.1001/jamanetworkopen.2024.61409.

ABSTRACT

IMPORTANCE: While acute alcohol use (AAU) is known to increase the risk of suicide significantly, the underlying mechanisms of this association are still understudied.

OBJECTIVE: To examine the association between AAU and the risk factors for suicide, focusing on the association between AAU and choice of suicide methods.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included data from the Korean National Investigations of Suicide Victims Study (KNIGHTS). The KNIGHTS dataset comprises nationally representative data encompassing nearly all suicide deaths in South Korea from January 1, 2013, to December 31, 2020. The study was analyzed from November 2 to 10, 2023.

MAIN OUTCOMES AND MEASURES: The main outcome was whether decedents who died by suicide had consumed alcohol before their death. Trained investigators conducted psychological autopsies by reviewing police reports of suicide deaths. Whether the decedent who died by suicide had consumed alcohol before death was determined from 3 sources: (1) confirmation by informants, (2) autopsy reports indicating a positive blood alcohol concentration, and (3) observations from police officers. Demographic characteristics, premortem psychiatric symptoms, and suicide characteristics, including method of suicide and presumed reasons for suicide, were examined. Hierarchical logistic regression models were used to examine the association between the contributing factors and AAU.

RESULTS: This study included 55 226 decedents who died by suicide (65.5% male), of whom 21 998 (39.8%) were under the influence of alcohol at the time of death. AAU was associated with being male (odds ratio [OR], 1.37 [95% CI, 1.31-1.44]); being middle aged (eg, from age 30 to 39 years: OR, 1.20 [95% CI, 1.06-1.35]); and having alcohol use disorder symptoms (OR, 13.28 [95% CI, 12.38-14.24]). Among suicide methods, gas, drug, and pesticide poisoning showed a positive association with AAU, with gas poisoning showing the highest OR (OR, 1.88 [95% CI, 1.61-2.20]). An interaction was found between age and suicide method, with older adults (eg, aged 80 years or older) having higher odds of AAU when using methods such as drug (OR, 6.28 [95% CI, 3.53-11.17]), pesticide (OR, 6.56 [95% CI, 3.86-11.13]), and gas (OR, 2.48 [95% CI, 1.52-4.04]) poisoning.

CONCLUSIONS AND RELEVANCE: The findings of this cross-sectional study suggest that AAU was associated with gas poisoning, as indicated by the ORs. Given that charcoal burning involves substantial preparation time, alcohol may have been deliberately used to facilitate planned suicide attempts. Furthermore, the deaths of older adults who consumed alcohol prior to suicide, even when using less lethal methods, highlight the critical need for monitoring and effectively managing alcohol use within this population.

PMID:39992652 | DOI:10.1001/jamanetworkopen.2024.61409

JAMA Netw Open. 2025 Feb 3;8(2):e2461495. doi: 10.1001/jamanetworkopen.2024.61495.

ABSTRACT

IMPORTANCE: Medical aid in dying (MAID) is legal in jurisdictions covering more than one-fifth of the US population and has been used by a largely White, educated population. The extent to which knowledge of MAID and preferences for personal use align with patterns of use is unknown.

OBJECTIVE: To evaluate knowledge among US adults of the legal status of MAID as well as interest in using MAID.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional, self-report online survey study used a national Prime Panels-based sample of US adults recruited between July 16 and August 10, 2024. A total of 3227 respondents aged 18 years or older from all US states and Washington, DC, were included. Individuals from states with legal MAID, aged 60 years or older, and members of racial and ethnic minority groups were oversampled.

MAIN OUTCOMES AND MEASURES: Knowledge of the legality of MAID in the US and in respondents’ state of residence as well as potential interest in future use of MAID. Descriptive statistics and χ2 tests were used to examine associations by demographic characteristics and place of residence.

RESULTS: Of 3227 respondents (mean [SD] age, 55.7 [17.4] years; 1839 women [57.0%]), 1654 (51.3%) did not know if MAID was legal the US, and 1638 (50.8%) did not know if MAID was legal in their state. Respondents in states where MAID is legal were more likely to know that MAID is legal in the US compared with those in states where MAID is not legal (728 of 2164 [33.6%] vs 216 of 1063 [20.3%]; P < .001). Across all respondents, 1420 (44.0%), including 96 of 222 Asian respondents (43.2%), 206 of 605 Black respondents (34.0%), and 129 of 308 Hispanic respondents (41.9%), reported they would definitely or probably consider MAID if they received a diagnosis of a terminal illness.

CONCLUSIONS AND RELEVANCE: In this online survey study of US adults, substantial interest in using MAID as well as significant knowledge gaps regarding the legality of MAID were reported. These findings highlight the need for public education, policy initiatives, and patient-clinician discussions to ensure equitable access to patient-centered end-of-life options and informed decision-making.

PMID:39992651 | DOI:10.1001/jamanetworkopen.2024.61495

JAMA Neurol. 2025 Feb 24. doi: 10.1001/jamaneurol.2024.5406. Online ahead of print.

ABSTRACT

IMPORTANCE: A leading cause of surgically remediable, drug-resistant focal epilepsy is focal cortical dysplasia (FCD). FCD is challenging to visualize and often considered magnetic resonance imaging (MRI) negative. Existing automated methods for FCD detection are limited by high numbers of false-positive predictions, hampering their clinical utility.

OBJECTIVE: To evaluate the efficacy and interpretability of graph neural networks in automatically detecting FCD lesions on MRI scans.

DESIGN, SETTING, AND PARTICIPANTS: In this multicenter diagnostic study, retrospective MRI data were collated from 23 epilepsy centers worldwide between 2018 and 2022, as part of the Multicenter Epilepsy Lesion Detection (MELD) Project, and analyzed in 2023. Data from 20 centers were split equally into training and testing cohorts, with data from 3 centers withheld for site-independent testing. A graph neural network (MELD Graph) was trained to identify FCD on surface-based features. Network performance was compared with an existing algorithm. Feature analysis, saliencies, and confidence scores were used to interpret network predictions. In total, 34 surface-based MRI features and manual lesion masks were collated from participants, 703 patients with FCD-related epilepsy and 482 controls, and 57 participants were excluded during MRI quality control.

MAIN OUTCOMES AND MEASURES: Sensitivity, specificity, and positive predictive value (PPV) of automatically identified lesions.

RESULTS: In the test dataset, the MELD Graph had a sensitivity of 81.6% in histopathologically confirmed patients seizure-free 1 year after surgery and 63.7% in MRI-negative patients with FCD. The PPV of putative lesions from the 260 patients in the test dataset (125 female [48%] and 135 male [52%]; mean age, 18.0 [IQR, 11.0-29.0] years) was 67% (70% sensitivity; 60% specificity), compared with 39% (67% sensitivity; 54% specificity) using an existing baseline algorithm. In the independent test cohort (116 patients; 62 female [53%] and 54 male [47%]; mean age, 22.5 [IQR, 13.5-27.5] years), the PPV was 76% (72% sensitivity; 56% specificity), compared with 46% (77% sensitivity; 47% specificity) using the baseline algorithm. Interpretable reports characterize lesion location, size, confidence, and salient features.

CONCLUSIONS AND RELEVANCE: In this study, the MELD Graph represented a state-of-the-art, openly available, and interpretable tool for FCD detection on MRI scans with significant improvements in PPV. Its clinical implementation holds promise for early diagnosis and improved management of focal epilepsy, potentially leading to better patient outcomes.

PMID:39992650 | DOI:10.1001/jamaneurol.2024.5406

J Mater Chem B. 2025 Feb 24. doi: 10.1039/d4tb02835j. Online ahead of print.

ABSTRACT

Novel and promising biomaterials for bone tissue engineering have been investigated over the years. Aiming to contribute to this progress, this study developed and evaluated polycaprolactone (PCL) scaffolds with 5% (w/w) 58S-bioactive glass (58S-BG) fabricated via melt electrowriting (MEW). Morphological and chemical characterization of the scaffolds was conducted. The biological potential was assessed in vitro with alveolar bone-derived mesenchymal stem cells through cytotoxicity, adhesion, protein production, alkaline phosphatase activity, and mineral nodule formation assays. In vivo, scaffolds implanted in rats were analyzed for biocompatibility, inflammation, and degradation using H&E staining and immunohistochemical markers for angiogenesis and macrophage polarization. Statistical analysis was performed at a 5% significance level. Appropriate fiber alignment but a higher fiber diameter was found for PCL + BG5% compared to PCL scaffolds (p = 0.002). EDS spectra confirmed the presence of BG’s chemical components for BG-laden scaffolds, attesting to BG particle incorporation into the filaments. Raman spectroscopy evidenced the chemical nature of the BG powder, and FTIR spectra revealed -OH stretching for PCL + BG5%, evidencing its hydrophilic potential. None of the scaffolds were cytotoxic, and BG-laden formulation increased cell viability after 7 days (p = 0.0006), also showing greater cell adhesion/spreading over time compared to pristine PCL scaffolds. BG’s presence also increased the mineral matrix formation (p ≤ 0.0021) over 21 days and retained ALP activity after 14 days (p = 0.705) compared to PCL. In vivo, PCL scaffolds retained fiber alignment and preserved their volume throughout the evaluation, showing minimal structural alteration. In contrast, PCL + BG5% scaffolds showed more visible structural changes at 28 days. Despite this, the PCL + BG5% formulation remained biocompatible and significantly promoted angiogenesis compared to pristine PCL scaffolds. In sum, BG-laden scaffolds were successfully melt electrowritten, retaining the scaffolds’ porous architecture, showing appropriate properties, including cell viability, adhesion, mineralized nodule deposition, biocompatibility, and angiogenesis, indicating that these materials are a promising alternative for enhancing bone tissue regeneration.

PMID:39992649 | DOI:10.1039/d4tb02835j