Study on the association between adverse drug reactions to opioids and gene polymorphisms: a case-case-control study.

OBJECTIVE: Adverse drug reactions (ADRs) caused by opioid drugs show individual differences. Our objective was to explore the association between gene polymorphism and ADRs induced by opioid drugs. METHODS: Evidence-based medical data analysis was conducted for genes related to ADRs induced by opioid drugs to select target genes. Sixty patients with cancer pain who had ADRs after taking opioid drugs (morphine, codeine, oxycodone) and 60 patients without ADRs after taking opioid drugs were used as the experimental group and control group, respectively. Then, we used polymerase chain reaction (PCR) or in situ hybridization to detect target genes. By combining with clinical data such as age, sex, dosage and duration of medication, the effect of gene polymorphism on the ADR of patients after taking opioid drugs was statistically analysed. RESULTS: Based on a database search and evidence-based medical data, we identified CYP2D6*10, CYP3A5*3, ABCB1, and OPRM1 as target genes for detection. The results of statistical analysis showed no significant difference in genotype distribution between the experimental group and the control group (p > 0.05). However, if 32 patients with ADRs after taking oxycodone and 32 controls were selected for comparison, the SPSS22.0 and SNPStats genetic models showed that the ABCB1 (062rs1045642) CT and TT genotypes correlated with the occurrence of ADRs (p < 0.05): the total number of CT + TT genotypes in the experimental group was 29 (90.62%), with 11 (34.37%) CT + TT genotypes types in the control group. CONCLUSION: Polymorphism of ABCB1 (062rs1045642) is related to ADRs caused by oxycodone, and the incidence of ADRs is higher with the allele T. Polymorphism of ABCB1 is expected to become a clinical predictor of ADRs to oxycodone, and attention should be given to the occurrence of serious ADRs in patients with ABCB1 (062rs1045642) CT and TT genotypes.

Aggressive fibromatosis near the incision after cervical spinal cord ependymoma: A case report.

Aggressive fibromatosis (AF), also known as ligamentoid fibromatosis and desmoid tumor, is a fibroblast clonoproliferative lesion located in the deep soft tissue. The present study reports the case of a 36-year-old female with AF who underwent cervical spinal cord ependymoma surgery. AF developed in the soft tissue of the neck adjacent to the incision site. The size of the neck AF increased rapidly over 2 years, and due to discomfort, the patient underwent initial surgical resection without any other combined treatment methods. When the patient was routinely reviewed at 6 months post-surgery, a recurrence of AF of the neck was found. The patient was recommended surgical resection and radiotherapy. This case report should improve the understanding of clinicians with regard to AF, and help the diagnostic process and treatment plan.

Differentiation of neurogenic tumours and pleomorphic adenomas in the parapharyngeal space based on texture analysis of T2WI.

BACKGROUND: The purpose of this study was to identify neurogenic tumours and pleomorphic adenomas of the parapharyngeal space based on the texture characteristics of MRI-T2WI. METHODS: MR findings and pathological reports of 25 patients with benign tumours in the parapharyngeal space were reviewed retrospectively (13 cases with pleomorphic adenomas and 12 cases with neurogenic tumours). Using PyRadiomics, the texture of the region of interest in T2WI sketched by radiologists was analysed. By using independent sample t-tests and Mann‒Whitney U tests, the selected texture features of 36 Gray Level Co-Occurrence Matrix (GLCM) and Gray Level Dependence Matrix (GLDM) were tested. A set of parameters of texture features showed statistically significant differences between the two groups, which were selected, and the diagnostic efficiency was evaluated via the operating characteristic curve of the subjects. RESULTS: The differences in the three parameters - small dependence low level emphasis (SDLGLE), low level emphasis (LGLE) and difference variance (DV) of characteristics - between the two groups were statistically significant (P < 0.05). No significant difference was found in the other indices. ROC curves were drawn for the three parameters, with AUCs of 0.833, 0.795, and 0.744, respectively. CONCLUSIONS: There is a difference in the texture characteristic parameters based on magnetic resonance T2WI images between neurogenic tumours and pleomorphic adenomas in the parapharyngeal space. For the differential diagnosis of these two kinds of tumours, texture analysis of significant importance is an objective and quantitative analytical tool.

Data mining techniques for detecting signals of adverse drug reaction of cardiac therapy drugs based on Jinan adverse event reporting system database: a retrospective study.

OBJECTIVE: Cardiac therapy drugs are widely used in the treatment of heart disease. However, the concern regarding adverse events (AEs) of cardiac therapy drugs have been rising. This study aimed to analyse cardiac therapy drug-related AEs using the Jinan adverse event reporting system (JAERS) database mining and conduct a comprehensive evaluation to provide safe medication information for patients. DESIGN: Retrospective observational study. SETTING: In this study, cardiac therapy drug-related AEs were detected using the JAERS database from January 2000 to March 2022. METHODS: Reports of cardiac therapy drug-related AEs were extracted from JAERS database, and the basic information of patients, reports and common AEs were analysed. Four disproportionality analysis methods, proportional reporting ratio (PRR), reporting odds ratio (ROR), Bayesian Confidence Propagation Neural Network (BCPNN), Medicines and Healthcare products Regulatory Agency (MHRA), were used to detect cardiac therapy drug-related signals. We further checked whether the detected signals exist on drug labels in China and two developed countries, the USA and Japan. RESULTS: In total, 168 314 AEs were reported, of which 4788 were associated with cardiac therapy drugs. Using the PRR, ROR, MHRA and BCPNN method, we detected 52 signals, 52 signals, 33 signals and 43 signals, respectively. Among the 52 signals, 14 were not included on the drug labels of China. One (isosorbide mononitrate-head bilges) was not included on the drug labels of the three countries. CONCLUSION: We identified 14 new cardiac therapy drug signals that did not appear on drug labels in China and 1 new signal that did not appear on drug labels in 3 counties. A causal link between cardiac therapy drugs and AEs should be evaluated in further studies.

Development of a drug risk analysis and assessment system and its application in signal excavation and analysis of 263 cases of fluoroquinolone-induced adverse reactions.

Background: Adverse drug reaction (ADR) signal mining is essential for assessing drug safety. However, the currently available methods for this are rather cumbersome. Objective: We aimed to develop a drug risk analysis and assessment system using Java language and conduct pharmacovigilance data mining for fluoroquinolones at our hospital. Methods: We used ADR data reported by Shandong Provincial Third Hospital between July 2007 and August 2021. The signal detection methods included proportional reporting ratio (PRR), reporting odds ratio (ROR), Bayesian Confidence Propagation Neural Network (BCPNN), Medicines and Healthcare products Regulatory Agency (MHRA). The BCPNN method was used as the reference standard for comparing the remaining three signal detection methods based on sensitivity, specificity, positive predictive value, negative predictive value, and Jorden index. Results: The hospital database contained a total of 2,621 ADR reports, among which 263 were attributed to fluoroquinolones. There were 391 fluoroquinolone-ADR pairs. Using the PRR, ROR, MHRA, and BCPNN method, we detected 13 signals, 13 signals, 10 signals, and 11 weak signals, respectively. After signal detection, levofloxacin and moxifloxacin were shown to induce high risk signals for mental and sleep disorders, with the signal intensity of moxifloxacin being the most significant. Compared with BCPNN, the PRR and ROR methods showed better sensitivity, whereas the MHRA method showed better specificity. Conclusion: We developed a drug risk analysis and assessment system that can help hospitals and other medical institutions to detect and analyse ADR signals in the self-reporting system database, and thus improve drug safety. Further, it indicates that the central nervous system damage caused by fluoroquinolones should be monitored closely, and thus provides a reference for the clinical application of these drugs.

Drug and therapeutics committee interventions in managing irrational drug use and antimicrobial stewardship in China.

Aim: This study aimed to investigate the key points in the transformation of the functions of the Drug and Therapeutics Committee (DTC) of the Shandong Provincial Third Hospital and how to provide full authority to its role in the control of rational drug use, especially in the management of antibiotic use. Method: A prescription review management group, antimicrobial stewardship group, and rational drug use service group were established under the DTC. From January 2016 to December 2021, each group played a role in promoting rational drug use and antimicrobial stewardship. In addition, we performed statistics on typical management cases, irrational drug use, bacterial resistance rate, and drug costs from 2015 to 2021 to evaluate the effect of management by the DTC. Results: Intervention by the DTC led to a significant reduction in prescribing errors (71.43%, p < 0.05), the intervention acceptance rate increased by 16.03%, and the problem solved rate increased by 32.41% (p < 0.05). Resistance rates of general spectrum antibiotics were reduced remarkably after the intervention. The quality of drug treatment was improved and patient drug expenses was continuously reduced. Conclusion: Giving full play to the functions of the DTC can significantly improve the level of drug treatment and reduce unreasonable drug use to save unnecessary drug expenses and slow the development of drug resistance.

Pharmacovigilance of cutaneous adverse drug reactions in associations with drugs and medical conditions: a retrospective study of hospitalized patients.

BACKGROUND: Cutaneous adverse drug reaction (CADR) is a common problem in clinical medication. This study aimed to investigate the correlation between clinical drug application and CADR occurrence as evidence for preventive strategies and rational clinical drug use. METHODS: We analyzed the characteristics of CADRs of 858 patients admitted to Shandong Provincial Third Hospital from March 2007 to December 2018. The most significant drugs concerning the common skin symptoms and their significance to CADR were investigated by case-non-case and multiple logistic regression analyses. RESULTS: A total of 266 drugs were involved in 858 cases of CADR. Among the ten most relevant medications, primarily antibiotics and herbal injections, and nutritional support drugs, potassium sodium dehydroandrographolide succinate injection, and cefoperazone sodium and sulbactam sodium injection were found to be 2.1 and 1.45 times statistically more prone to CADRs than to other adverse drug reactions (ADRs), respectively. The main route of administration was intravenous (63.16%), with oral administration accounting for 25.19%. There were 747 cases of ADR, 71 of severe ADR, 2 of new and severe ADRs, and 38 cases of new ADR. Overall, 100 cases of CADR exhibited abnormal alanine aminotransferase, aspartate aminotransferase, and serum creatinine levels. The predictive factors for severe CADR occurrence included allergy and smoking histories, cefoperazone sodium, sulbactam sodium injection, levofloxacin lactate and sodium chloride injection. CONCLUSIONS: Drug-induced CADR symptoms are commonly associated with other ARDs, predominantly rashes and pruritus, and are often accompanied by some medical conditions, especially liver and kidney damage. Detailed attention to a patient's primary diseases, allergy history, and drug safety profile could help prevent or reverse CADR in most patients.

Evaluating the effectiveness of drug and therapeutics committees (DTCs) in controlling irrational drug use: A retrospective analysis.

WHAT IS KNOWN AND OBJECTIVE: This study aimed to explore methods to optimize the function of Drug and Therapeutics Committees (DTCs) in controlling irrational drug use. Clinical pharmacologists contribute their specific knowledge and skills to DTCs and help guide rational therapeutics. The DTC is the highest organization of hospital pharmacy management. METHODS: From January 2016 to August 2021, the DTC promoted the optimization of clinical drug treatment schemes and reduced unreasonable drug use by improving the organizational framework, clarifying the division of functions, regularly monitoring drug use, organizing expert comments, scientific decision-making and functional intervention. During this time, we statistically analysed typical management cases, irrational drug use and drug cost to evaluate the effectiveness of the DTC's management. RESULTS AND DISCUSSION: The DTC's intervention led to a significant reduction in prescribing errors (65.98%, p < 0.05); the intervention acceptance rate increased by 16.37%; and the rate of problem resolution increased by 45.84% (p < 0.05). The level of drug treatment was improved, and the proportion of patients' drug expenses was reduced. WHAT IS NEW AND CONCLUSION: The DTC carried out a series of continuous improvement work that played a significant normative role in clinical drug use. Giving more power to the DTCs can significantly improve the level of drug treatment and reduce unreasonable drug use, which reduces unnecessary drug expenses.

Prediction of the degree of pathological differentiation in tongue squamous cell carcinoma based on radiomics analysis of magnetic resonance images.

BACKGROUND: Tongue squamous cell carcinoma (TSCC) is one of the most difficult malignancies to control. It displays particular and aggressive behaviour even at an early stage. The purpose of this paper is to explore the value of radiomics based on magnetic resonance fat-suppressed T2-weighted images in predicting the degree of pathological differentiation of TSCC. METHODS: Retrospective analysis of 127 patients with TSCC who were randomly divided into a primary cohort and a test cohort, including well-differentiated, moderately differentiated and poorly differentiated. The tumour regions were manually labelled in fat-suppressed T2-weighted imaging (FS-T2WI), and PyRadiomics was used to extract radiomics features. The radiomics features were then selected by the least absolute shrinkage and selection operator (LASSO) method. The model was established by the logistic regression classifier using a 5-fold cross-validation method, applied to all data and evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity and specificity. RESULTS: In total, 1132 features were extracted, and seven features were selected for modelling. The AUC in the logistic regression model for well-differentiated TSCC was 0.90 with specificity and precision values of 0.92 and 0.78, respectively, and the sensitivity for poorly differentiated TSCC was 0.74. CONCLUSIONS: The MRI-based radiomics signature could discriminate between well-differentiated, moderately differentiated and poorly differentiated TSCC and might be used as a biomarker for preoperative grading.

Application of first-order feature analysis of DWI-ADC in rare malignant mesenchymal tumours of the maxillofacial region.

BACKGROUND: To research the first-order features of apparent diffusion coefficient (ADC) values on diffusion-weighted magnetic resonance imaging (DWI) in maxillofacial malignant mesenchymal tumours. METHODS: The clinical data of 12 patients with rare malignant mesenchymal tumours of the maxillofacial region (6 cases of sarcoma and 6 cases of lymphoma) treated in the hospital from May 2018 to June 2020 and were confirmed by postoperative pathology were retrospectively analyzed. The patients were all examined by 1.5T magnetic resonance imaging. PyRadiomics were used to extract radiomics imaging first-order features. Group differences in quantitative variables were examined using independent-samples t-tests. RESULTS: The voxels number of ADCmean and ADCmedian of sarcoma tissues were 44.9124 and 44.2064, respectively, significantly higher than those in lymphoma tissues (ADCmean (- 68.8379) and ADCmedian (- 74.0045)), the difference considered statistically significant, so do the ADCkurt and ADCskew. CONCLUSIONS: The statistical difference of ADCmean and ADCmedian is significant, it is consistent with the outcome of the manual measurement of the ADC mean value of the most significant cross-section of twelve cases of lymphoma. Development of tumour volume based on the ADC parameter map of DWI demonstrates that the first-order ADC radiomics features analysis can provide new imaging markers for the differentiation of maxillofacial sarcoma and lymphoma. Therefore, first-order ADC features of ADCkurt combined ADCskew may improve the diagnosis level.

Pharmacist-led, prescription intervention system-assisted feedback to reduce prescribing errors: A retrospective study.

WHAT IS KNOWN AND OBJECTIVE: Prescribing errors are prevalent in hospital settings, with provision of feedback recommended to support prescribing by doctors. To evaluate the impact of a pharmacist-led prescription intervention system on prescribing error rates and to measure intervention efficiency. METHODS: All prescribers in Shandong Provincial Third Hospital received feedback from ward pharmacists using a pharmacist-led prescription intervention system. The prescribing error rate was calculated from Oct 2019 to December 2020. After the intervention was applied, the rates of PASS 1 (System pass), PASS 2 (Pharmacist pass) and PASS 3 (Pharmacist-doctor pass) events and the feedback time were calculated each month. RESULTS AND DISCUSSION: Irrational use of drugs was reduced and the prescription rate increased significantly. The error rate reduced from 6.94% to 1.96%, representing an estimated 71.76% decrease overall (p < 0.05). The PASS 1 rate gradually increased from 88% to 96% (p < 0.05), the PASS 2 rate gradually decreased from 5.06% to 2.04% (p < 0.05), the PASS 3 rate gradually decreased from 6.94% to 1.96% (p < 0.05). WHAT IS NEW AND CONCLUSION: The pharmacist-led prescription intervention system has the potential to reduce prescribing errors and improve prescribing outcomes and patient safety.

Defect Engineering of Nanoscale Hf-Based Metal-Organic Frameworks for Highly Efficient Iodine Capture.

With the rapid development of the nuclear industry, how to deal with radioactive iodine waste in a timely and effective manner has become an important issue to be solved urgently. Herein, the defect-engineering strategy has been applied to develop a metal-organic framework (MOF)-based solid adsorbent by using the classical UiO-type Hf-UiO-66 as an example. After simple acid treatment, the produced defect-containing Hf-UiO-66 (DHUN) not only retains its topological structure, high crystallization, and regular shape but also shows a great increase in the Brunauer-Emmett-Teller value and pore size in comparison with the original Hf-UiO (HUN). These formed defects within DHUN have been demonstrated to be important for the great enhancement of the iodine capture and following application in computed tomography imaging in vitro. This present work gives a new insight into the control and formation of defect sites, and this simple and efficient defect-engineering strategy also shows great promise for the development of novel solid adsorbents and other functional MOF materials.

Vaginal drug delivery approaches for localized management of cervical cancer.

Cervical cancer or cervical intraepithelial neoplasia (CIN) remain a major public health problem among women globally. Traditional methods such as surgery are often associated with possible complications which may impact future pregnancies and childbirth especially for young female patients. Vagina with a high contact surface is a suitable route for the local and systemic delivery of drugs but its abundant mucus in continuous exchange presents a barrier for the popularization of conventional vaginal formulations including suppositories, gel, patch, creams and so on. So the development of new pharmaceutical forms based on nanotechnology became appealing owing to its several advantages such as mucosa penetration, bioadhesion, controlled drug release, and decreased adverse effects. This review provided an overview of the development of topical treatment of cervical cancer or CIN through vaginal drug delivery ranging from conventional vaginal formulations to new nanocarriers to the newly developed phototherapy and gene therapy, analyzing the problems faced by current methods used, and advising the developing trend in future. The methods of establishing preclinical animal model are also discussed.

Analysis of the impact of antimicrobial management and rational use of antibiotics.

OBJECTIVE: The scientific antimicrobial management strategy (AMS) was used to standardise the clinical use of antibiotics and optimise the anti-infection treatment protocol. METHODS: By formulating antibiotic use indicators and policy interventions, carrying out prescription audits and drug analysis by pharmacists, and establishing an early warning mechanism for bacterial drug resistance, we formed a long-term and scientific antimicrobial management strategy. RESULTS: From 2012 to 2017, the clinical antibiotics use indicators appeared to trend downward. The rate of antibiotic use in outpatients, the rate of antibiotic use in hospitalised patients, and the antimicrobial use density decreased by 40.36%, 20.93%, and 10.71%, respectively, and the per capita drug cost of antibiotics in outpatients and inpatients decreased. The microbiological susceptibility test rate of antibiotics in hospitalised patients increased each year, and the resistance rate of the main detected bacteria did not significantly increase in the last 6 years. In the evaluation of rational drug use, the use of antibiotics has become more reasonable and standardised, and irrational drug use has been significantly reduced, but we still need to strengthen the optimisation of treatment prescription. CONCLUSIONS: Scientific management can promote the rational use of antibiotics, reduce the expense of drug use and slow the development of drug resistance, but we need to further optimise the prescription of antibiotics to improve the level of drug treatment.

Risks in clinical applications of oseltamivir phosphate in the real world.

A retrospective analysis was conducted on the use of oseltamivir phosphate in outpatients and inpatients in our hospital from February 2016 to February 2019. The indications, purposes, dosage, combination, and adverse reactions were analysed focussing on the rationality and safety of oseltamivir. The relationship between adverse reactions and age, allergic history, underlying diseases, and combined drug use were analysed to find the risk factors associated therewith. A total of 1795 adult patients and 3199 children were treated with oseltamivir phosphate. In the adult group 1481 patients (82.5%) and in the child group, 2602 patients (81.3%) received oseltamivir for therapeutic ourposes. The main clinical diagnoses were upper respiratory tract infection, bronchitis, and pneumonia. Only 767 cases (15.2%) were confirmed as influenza virus infection by virological examination, the rest were suspected influenza cases and clinically diagnosed influenza cases. For preventive drug use, an adult group comprising 314 cases (17.5%) and a child group with 597 cases (18.7%) were identified. The dosage and course of treatment were more standardised, but there were too many types of combined drugs, and the indications of preventive use were insufficient in some cases. A total of 106 adverse drug reactions (2.12%) was recorded, mainly affecting the digestive system and neuropsychiatric systems. The rate of adverse drug reactions was related to age and the number of drug combinations. Attention should also be paid to age, combination of drugs, and allergy history.

Renal clearable Hafnium-doped carbon dots for CT/Fluorescence imaging of orthotopic liver cancer.

Carbon dots (CDs) are emerging as powerful nanoprobes for multiple-model bioimaging. Nowadays, orthotopic xenograft models attract increasing attention because of their superiorities of duplicating the tumor microenvironment. However, compared with the extensive study of subcutaneous xenograft tumors, less attention has been paid to CDs for in vivo orthotopic tumor imaging. Furthermore, it is very desirable for a nanoprobe to achieve preferential accumulation at the tumor site and efficient renal clearance. In this work, a novel kind of Hafnium-doped CDs (HfCDs) were successfully prepared via a simple one-pot pyrolysis method. The significant advantages including robust stability, good biocompatibility, excellent water solubility, remarkable computed tomography (CT) contrast performance and preferential tumor accumulation capability endow HfCDs with particular functions of CT/fluorescence imaging of orthotopic liver cancer initially. More importantly, HfCDs could locate at the tumor site and achieve the rapid imaging within 1 min. The findings of the current study represent a facile and universal approach to fabricate outstanding renal clearable multimodal imaging nanoprobes with great potential for clinical diagnosis.

Integration of metal-organic framework with a photoactive porous-organic polymer for interface enhanced phototherapy.

Porphyrin-based porous organic polymers are highly potential candidates for cancer theranostics. However, un-controllable particle size and unclear photoactive mechanisms have been deemed to be "Achilles' heels" for their biomedical application. Herein, a facile self-template strategy has been applied to integrate two types of porous materials to build the MOF@POP-PEG nanocomposite (named HUC-PEG). As-synthesized HUC-PEG exhibited controllable particle shape and size, good biocompatibility, and better colloidal stability. Importantly, synergy "0 + 1 > 1" interface effects have been demonstrated to simultaneously enhance both the generation of more singlet oxygen (1O2) for photodynamic therapy (PDT) and local hyperthermia for photothermal therapy (PTT), thus to achieve favorable proliferation inhibition of tumor cell both in vitro and in vivo. Moreover, the strong X-ray attenuating ability of Hf element and excellent photothermal conversion efficacy endow this nanocomposite with computed tomography (CT)/photothermal imaging functions. We believe that our ingenious design may open a new horizon for the preparation of nanoscale POP-based therapeutic agents and also realize a paradigm shift in the understanding of photoactive mechanism in porous materials.

A Multi-Functional Silicon Nanoparticle Designed for Enhanced Osteoblast Calcification and Related Combination Therapy.

Implant materials applied in bone defect commonly focus on the inducement of bone regeneration and neglect to cure complications including bacterial infection and inflammation, which may result in delayed unions or even amputation. In this study, a microporous silica nanoparticle-poly(N-isopropylacrylamide-b-(2-(dimethylamino)ethyl methacrylate) is synthesized for loading DXMS and the ECM-derived peptide (Sequence: Succinic acid-GTPGPQGIAGQRGVV) in order to enhance the osteoblast calcification and relieve related symptoms. Positively charged PDMA blocks endow the nanoparticle with the antimicrobial property. Moreover, the combination of DXMS makes it have the ability of anti-inflammation and promoting calcification formation. Furthermore, incorporation of the peptide leads to a significant improvement of mineralization and alkaline phosphatase expression in the preosteoblast. After intramuscular implantation in mice for four weeks, the results indicate the composite nanoparticle can promote ectopic bone formation. These combined properties make the composite silicon nanoparticle a promising osteogenic drug appropriate for further study in bone repair and related combination therapy.

Robust organic nanoparticles for noninvasive long-term fluorescence imaging.

Fluorescence imaging is a non-invasive imaging technique, which facilitates the visualization of sub-cellular components in cells with high sensitivity and selectivity. Up to now, only indocyanine green (ICG) has been approved as a diagnostic reagent for intravenous application. But the intrinsic disadvantage of ICG has spurred more research attention to exploit new fluorescent materials in imaging fields. In the last decade, many materials, including inorganic and organic materials, have been developed for fluorescence imaging. There are some reviews about fluorescence bioimaging. In this review, we will summarize and highlight the reported organic nanoparticles for noninvasive long-term bioimaging. According to the emitting mechanism, fluorescent nanoparticles obtained from fluorophores with aggregation-caused quenching and aggregation-induced emission features are discussed respectively. Finally, we come up with some key issues and challenges in the future and clinical translation.

Development of Organic/Inorganic Compatible and Sustainably Bioactive Composites for Effective Bone Regeneration.

In this paper, we demonstrate a strategy of covalently bonding bioactive molecules onto inorganic hydroxyapatite (HAp) to improve the compatibility between organic and inorganic components and endow the bone composites with sustainable bioactivity. Bone morphogenetic protein-2 (BMP-2) peptide covalently immobilized nano-hydroxyapatite (nHAp-BMP-2) is developed to preserve the bioactivity and slow the release of the BMP-2 peptide. Then nHAp-BMP-2 was further incorporated into an ultraviolet-curable mixture of gelatin methacrylamide (GelMA) and four-armed PEG methacrylamide (four-armed PEGMA) to form a Gel/(nHAp-BMP-2) composite. The hydrogen bonding between gelatin and BMP-2 on nHAp-BMP-2 enhanced the compatibility between inorganic and organic components. The Gel/(nHAp-BMP-2) composite exhibited superior biocompatibility caused by gelatin and nHAp-BMP-2, except in a two-dimensional cell culture, the hydrogel was also capable of a three-dimensional cell culture. In addition, the introduction of nHAp-BMP-2 had a positive influence on bone marrow mesenchymal stem cell proliferation, differentiation, and the subsequent calcification on the composite. After treatment of a rat calvarial defect model for 12 weeks, the Gel/(nHAp-BMP-2) group showed the largest new bone volume and the highest ratio of new bone (50.54 ± 13.51 mm3 and 64.38 ± 17.22%, respectively) compared to those of the other groups. These results demonstrate that this way of controlling BMP-2 release is effective and the Gel/(nHAp-BMP-2) composite has great potential in bone regeneration therapy.