Progesterone Enhances Niraparib Efficacy in Ovarian Cancer by Promoting Palmitoleic-Acid-Mediated Ferroptosis.

Poly (adenosine 5'-diphosphate-ribose) polymerase inhibitors (PARPi) are increasingly important in the treatment of ovarian cancer. However, more than 40% of BRCA1/2-deficient patients do not respond to PARPi, and BRCA wild-type cases do not show obvious benefit. In this study, we demonstrated that progesterone acted synergistically with niraparib in ovarian cancer cells by enhancing niraparib-mediated DNA damage and death regardless of BRCA status. This synergy was validated in an ovarian cancer organoid model and in vivo experiments. Furthermore, we found that progesterone enhances the activity of niraparib in ovarian cancer through inducing ferroptosis by up-regulating palmitoleic acid and causing mitochondrial damage. In clinical cohort, it was observed that progesterone prolonged the survival of patients with ovarian cancer receiving PARPi as second-line maintenance therapy, and high progesterone receptor expression combined with low glutathione peroxidase 4 (GPX4) expression predicted better efficacy of PARPi in patients with ovarian cancer. These findings not only offer new therapeutic strategies for PARPi poor response ovarian cancer but also provide potential molecular markers for predicting the PARPi efficacy.

Association between sarcopenia and osteoarthritis among the US adults: a cross-sectional study.

The association between sarcopenia and OA still presents many uncertainties. We aimed to assess whether sarcopenia is associated with occurrence of OA in US adults. We conducted a cross-sectional study consisting of 11,456 participants from National Health and Nutrition Examination Survey 1999-2006. Sarcopenia was defined by a low muscle mass. The skeletal muscle index (SMI) was calculated as the appendicular skeletal muscle mass divided by body mass indexes (BMI) or body weight. OA status was assessed by using self-reported questionnaire. We evaluated the association between sarcopenia and OA using multivariate regression models. In addition, subgroup and interaction analysis were performed. Sarcopenia was associated with OA when it was defined by the BMI-adjusted SMI (OR = 1.23 [95% CI, 1.01, 1.51]; P = 0.038) and defined by the weight-adjusted SMI (OR = 1.30 [95% CI, 1.10, 1.55]; P = 0.003). Subgroup and interaction analysis found that the strongest positive association mainly exists in smoker (OR = 1.54 [95% CI, 1.21, 1.95], Pint = 0.006), and this association is not significant in other groups. In conclusion, we found that sarcopenia was associated with occurrence of OA. Subgroup analysis revealed that the association between sarcopenia and OA was more pronounced in smoker. Further well-designed prospective cohort studies are needed to assess our results.

Cellular metabolism: A key player in cancer ferroptosis.

Cellular metabolism is the fundamental process by which cells maintain growth and self-renewal. It produces energy, furnishes raw materials, and intermediates for biomolecule synthesis, and modulates enzyme activity to sustain normal cellular functions. Cellular metabolism is the foundation of cellular life processes and plays a regulatory role in various biological functions, including programmed cell death. Ferroptosis is a recently discovered form of iron-dependent programmed cell death. The inhibition of ferroptosis plays a crucial role in tumorigenesis and tumor progression. However, the role of cellular metabolism, particularly glucose and amino acid metabolism, in cancer ferroptosis is not well understood. Here, we reviewed glucose, lipid, amino acid, iron and selenium metabolism involvement in cancer cell ferroptosis to elucidate the impact of different metabolic pathways on this process. Additionally, we provided a detailed overview of agents used to induce cancer ferroptosis. We explained that the metabolism of tumor cells plays a crucial role in maintaining intracellular redox homeostasis and that disrupting the normal metabolic processes in these cells renders them more susceptible to iron-induced cell death, resulting in enhanced tumor cell killing. The combination of ferroptosis inducers and cellular metabolism inhibitors may be a novel approach to future cancer therapy and an important strategy to advance the development of treatments.

Research and publication trends on knee osteoarthritis and cellular senescence: a bibliometric analysis.

Background: Cellular senescence is associated with age-related pathological changes, senescent cells promote the development of knee osteoarthritis. A better understanding between knee osteoarthritis and cellular senescence may enhance the effectiveness of therapies that aim to slow or stop the progression of this disease. Purpose: This study aimed to systematically analyze and visualize the publication trends, research frontiers and current research hotspots of knee osteoarthritis and cellular senescence by using bibliometrics. Methods: The publication search was performed on the Web of Science Core Collection database for documents published from 1992 to 2023. VOSviewer, Citespace, R package Bibliometrix and Microsoft Office Excel were used to study the characteristics of the publications. The publication number, countries, institutions, authors, journals, citations and co-citations, keywords were analyzed. Results: A total of 1,074 publications were analyzed, with an average annual growth rate of 29.89%. United States accounted for the biggest contributor, ranked first in publications and citations. Publications of this field were published in 420 journals, OSTEOARTHRITIS and CARTILAGE was the most influential. A total of 5,657 authors contributed to this research. The most productive author was Lotz, MK (n = 31, H-index = 22, Total citation = 2,619), followed by Loeser, R.F (n = 16, H-index = 14, Total citation = 2,825). However, the collaboration between authors was relatively weak. Out of the 1,556 institutions involved, 60% were from the United States. Scripps Research ranked first with 25 papers and a total of 2,538 citations. The hotspots of this field had focused on the pathomechanisms (e.g., expression, inflammation, apoptosis, autophagy, oxidative stress) and therapeutics (e.g., stem cell, platelet-rich plasma, transplantation, autologous chondrocytes, repair), and the exploration of Senolytics might be the important direction of future research. Conclusion: Research on the cross field of knee osteoarthritis and cellular senescence is flourishing. Age-related pathomechanism maps of various cells in the joint and the targeted medicines for the senescent cells may be the future trends. This bibliometric study provides a comprehensive analysis of this cross field and new insights into future research.

[Relationship between intramuscular fat content in the quadriceps muscle and clinical severity in patients with knee osteoarthritis].

OBJECTIVE: To explore relationship between intramuscular fat content of quadriceps femoris and clinical severity of knee osteoarthritis (KOA). METHODS: Totally 30 KOA patients were selected from February 2021 to June 2021, including 6 males and 24 females, aged with an average of (64.20±9.19) years old, and body mass index (BMI) was (24.92±3.35) kg·m-2. Patients were divided into relative severe leg (RSL) and relative moderate leg (RML) according to severity of pain on visual analogue scale(VAS). Musculoskeletal ultrasound was used to collect muscle images of quadriceps muscles on both sides of the patient, and Image J was used to analyze echo intensity (EI) of each muscle. Both VAS and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were used to assess pain and function. Quadriceps muscle EI on both sides of patients was compared. Pearson correlation analysis was conducted to analyze correlation between quadriceps muscle EI value between RSL and RML, and linear regression was used to analyze relationship between each muscle EI and VAS and WOMA scores of patients. RESULTS: The EI of RSL lateral vastus lateralis (VL) was 123.78±36.25 and RSL vastus medialis (VM) was 109.46±30.36 which were significantly higher than those of 108.03±31.34 and 93.32±26.04 of RML (P<0.05), but there was no statistical significance in EI values of rectus femoris (RF) on both sides (P>0.05). EI values of VL and VM on both sides were significantly correlated (P<0.05). There was a significant positive correlation between VM EI value and VAS score in RSL and RML (P<0.05). VM EI values in RSL were positively correlated with total WOMAC (P<0.05), and VM VL EI values in RML were positively correlated with total WOMAC score (P<0.05). CONCLUSION: Intramuscular fat content of quadriceps is closely related to severity of clinical symptoms in KOA patients, and the most obvious one is VM. Therefore, the intramuscular fat content of quadriceps may be an objective indicator to evaluate severity of KOA patients. At the same time, reducing intramuscular fat content of the quadriceps muscle of KOA patients may be a new direction for the prevention and treatment of KOA.

Organoids: opportunities and challenges of cancer therapy.

Organoids are a class of multicellular structures with the capability of self-organizing and the characteristic of original tissues, they are generated from stem cells in 3D culture in vitro. Organoids can mimic the occurrence and progression of original tissues and widely used in disease models in recent years. The ability of tumor organoids to retain characteristic of original tumors make them unique for tumorigenesis and cancer therapy. However, the history of organoid development and the application of organoid technology in cancer therapy are not well understood. In this paper, we reviewed the history of organoids development, the culture methods of tumor organoids establishing and the applications of organoids in cancer research for better understanding the process of tumor development and providing better strategies for cancer therapy. The standardization of organoids cultivation facilitated the large-scale production of tumor organoids. Moreover, it was found that combination of tumor organoids and other cells such as immune cells, fibroblasts and nervous cells would better mimic the microenvironment of tumor progression. This might be important developing directions for tumor organoids in the future.

Tongbi Huoluo Decoction alleviates cartilage degeneration in knee osteoarthritis by inhibiting degradation of extracellular matrix.

BACKGROUND: Knee osteoarthritis (KOA) is an age-related degenerative disease characterized by abrasion of articular cartilage. Tongbi Huoluo Decoction (TBHLD) has been transformed from the famous traditional Chinese medicine Duhuo Jisheng Decoction, which can effectively alleviate pain symptoms in KOA. However, the active components and mechanisms of TBHLD in treating KOA have not yet been elucidated. The purpose of the study was to demonstrate the molecular mechanism of TBHLD in treating KOA. METHODS: The components and targets of TBHLD and KOA were collected from multiple databases, and the protein to protein interaction (PPI) network was constructed. Next, we performed topological calculation and enrichment analysis. Besides, we performed virtual screening for molecular docking and molecular dynamics simulation (MDS). Furthermore, the vitro and vivo experiments were performed to evaluate the validity and mechanism of TBHLD. RESULTS: 206 active components and 187 potential targets were screened from Tongbi Huoluo Decoction. A total of 50 intersecting genes were identified between TBHLD and KOA, 20 core targets were calculated by network topology analysis. The core targets were enriched in the ECM interaction pathways. The results of virtual screening for molecular docking and MDS showed that the active components of TBHLD had steady binding conformations with core genes. Moreover, we identified 32 differential serum components in TBHLD-containing serum using LC-MS, including 22 upregulated and 10 downregulated serum components. TBHLD improved the proliferation activity of OA chondrocytes, decreased the expression of Col1a1, Col1a2, Mmp2, Mmp13 in OA chondrocytes, ameliorated the cartilage lesions and restored the cartilage abrasion. CONCLUSION: TBHLD inhibited degradation of cartilage ECM by regulating the expression of type I collagens and Mmps to ameliorate cartilage degeneration in KOA.

Metabolic reprogramming and epigenetic modifications in cancer: from the impacts and mechanisms to the treatment potential.

Metabolic reprogramming and epigenetic modifications are hallmarks of cancer cells. In cancer cells, metabolic pathway activity varies during tumorigenesis and cancer progression, indicating regulated metabolic plasticity. Metabolic changes are often closely related to epigenetic changes, such as alterations in the expression or activity of epigenetically modified enzymes, which may exert a direct or an indirect influence on cellular metabolism. Therefore, exploring the mechanisms underlying epigenetic modifications regulating the reprogramming of tumor cell metabolism is important for further understanding tumor pathogenesis. Here, we mainly focus on the latest studies on epigenetic modifications related to cancer cell metabolism regulations, including changes in glucose, lipid and amino acid metabolism in the cancer context, and then emphasize the mechanisms related to tumor cell epigenetic modifications. Specifically, we discuss the role played by DNA methylation, chromatin remodeling, noncoding RNAs and histone lactylation in tumor growth and progression. Finally, we summarize the prospects of potential cancer therapeutic strategies based on metabolic reprogramming and epigenetic changes in tumor cells.

Comparison of the asymmetries in muscle mass, biomechanical property and muscle activation asymmetry of quadriceps femoris between patients with unilateral and bilateral knee osteoarthritis.

Background: More and more attention has been paid to the research of muscle mass and muscle quality of quadriceps femoris (QF) in knee osteoarthritis (KOA). This study aimed to explore the asymmetric changes of muscle mass, biomechanical property and muscle activation in the inter-limbs QF of KOA patients, and tried to provide a novel insight for the evaluation, prevention and treatment of KOA. Methods: A total of 56 Participants with unilateral or bilateral KOA were included in this study: 30 patients with unilateral pain and 26 patients with bilateral pain were assigned to the bilateral group (BG) and unilateral group (UG), respectively. The symptom severity of bilateral lower limbs was evaluated by visual analogue scale, and the relatively serious leg (RSL) and relatively moderate leg (RML) were classified. The thickness of rectus femoris (RF), vastus intermedius (VI), vastus medialis (VM) and vastus lateralis (VL) were measured by ultrasound. The Shear wave elastography (SWE) techniqie was used to measure the shear modulus of RF, VM and VL. Surface electromyography (sEMG) was used to assess the root mean square (RMS) of the RF, VM, and VL during straight leg raising in a sitting position and squatting task. We calculated the asymmetry indexes of inter-limbs for the corresponding indices of the measured muscles. Result: Thickness of RF, VI and VL of RSL was lower than those on RML (p < 0.05), and thickness of VM was lower more significant (p < 0.01). Thickness of RF, VI and VL of RSL was also lower than those of RML in BG (p < 0.05), however, there was no significant difference in VM thickness (p > 0.05). There were no significant difference in Asymmetry indexes of all measured muscle thickness between the two groups (p > 0.05). The Shear modulus of RF, VM, and VL in the RML of UG and BG was higher than those in the RSL (p < 0.05). In sitting and straight leg raising task, the RMS of RF, VM and VL in RML were higher than those in RSL, UG and BG both showed this trend (p < 0.05). About squatting task, in UG, the RMS of the three muscles in RML of patients were also higher than those in the RSL (p < 0.05). However, the difference was not significant in BG (p > 0.05). In the straight leg raising task, the asymmetry indexes of RMS in RF, VM, and VL of both the two groups were positively correlated with VAS scores (p < 0.05). Conclusion: The muscle thickness, shear modulus and muscle activation electromyography of QF in RML were higher than those of RSL in unilateral KOA patients. The VM of RML in bilateral KOA patients may show muscle thickness degeneration earlier, which is closer to the VM of RSL. The shear modulus of RF, VM, and VL were higher on the RML side during the single-leg task, but there may be passive compensation for muscle activation in both lower limbs during the bipedal task. In conclusion, there is a general asymmetry of QF muscle mass, biomechanics Characteristic and performance in patients with KOA, which may provide new ideas for the assessment, treatment and rehabilitation of the disease.

Copper-containing chitosan-based hydrogels enabled 3D-printed scaffolds to accelerate bone repair and eliminate MRSA-related infection.

Bone defect combined with drug-resistant bacteria-related infection is a thorny challenge in clinic. Herein, 3D-printed polyhydroxyalkanoates/ß-tricalcium phosphate (PHA/ß-TCP, PT) scaffolds were prepared by fused deposition modeling. Then copper-containing carboxymethyl chitosan/alginate (CA/Cu) hydrogels were integrated with the scaffolds via a facile and low-cost chemical crosslinking method. The resultant PT/CA/Cu scaffolds could promote not only proliferation but also osteogenic differentiation of preosteoblasts in vitro. Moreover, PT/CA/Cu scaffolds exhibited a strong antibacterial activity towards a broad-spectrum of bacteria including methicillin-resistant Staphylococcus aureus (MRSA) through inducing the intercellular generation of reactive oxygen species. In vivo experiments further demonstrated that PT/CA/Cu scaffolds significantly accelerated bone repair of cranial defects and efficiently eliminated MRSA-related infection, showing potential for application in infected bone defect therapy.

Clinical significance and integrative analysis of the cuproptosis-associated genes in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSC) is a kind of malignant tumor originating from the oropharynx, larynx, nasopharynx and oral cavity. The incidence of HNSC is increasing and it is the sixth malignant tumor in the world at present. "Cuprotosis" is a novel cuper-dependent cell death mode that is closely related to mitochondrial respiration. Tumorigenesis is closely related to the dysregulation of cell death. However, the relationship between cuprotosis and HNSC remains unclear. Here, we investigated the association between 10 cuprotosis-associated genes (CAGs) and HNSC using multi-omics public data. We found that CAGs had abnormal expression and significant genetic changes in HNSC, especially CDKN2A with 54% mutation rate. Expression of CAGs significantly correlates with the prognosis of HNSC patients. Moreover, the CAGs expression is correlated with the immune checkpoints expression and immune cells infiltration. These CAGs expression was associated with multiple drugs sensitivity of cancer cells, such as cisplatin and docetaxel. These findings indicate that CAGs are likely to serve an essential role in the diagnosis, prognosis, immunotherapy and drug therapy prediction of HNSC.

Exosomal cargos-mediated metabolic reprogramming in tumor microenvironment.

Metabolic reprogramming is one of the hallmarks of cancer. As nutrients are scarce in the tumor microenvironment (TME), tumor cells adopt multiple metabolic adaptations to meet their growth requirements. Metabolic reprogramming is not only present in tumor cells, but exosomal cargos mediates intercellular communication between tumor cells and non-tumor cells in the TME, inducing metabolic remodeling to create an outpost of microvascular enrichment and immune escape. Here, we highlight the composition and characteristics of TME, meanwhile summarize the components of exosomal cargos and their corresponding sorting mode. Functionally, these exosomal cargos-mediated metabolic reprogramming improves the "soil" for tumor growth and metastasis. Moreover, we discuss the abnormal tumor metabolism targeted by exosomal cargos and its potential antitumor therapy. In conclusion, this review updates the current role of exosomal cargos in TME metabolic reprogramming and enriches the future application scenarios of exosomes.

Reliability of foot posture index (FPI-6) for evaluating foot posture in patients with knee osteoarthritis.

Objective: To determine the reliability of FPI-6 in the assessment of foot posture in patients with knee osteoarthritis (KOA). Methods: Thirty volunteers with KOA (23 females, 7 males) were included in this study, assessed by two raters and at three different moments. Inter-rater and test-retest reliability were assessed with Cohen's Weighted Kappa (Kw) and Intraclass Correlation Coefficient (ICC). Bland-Altman plots and respective 95% limits of agreement (LOA) were used to assess both inter-rater and test-retest agreement and identify systematic bias. Moreover, the internal consistency of FPI-6 was assessed by Spearman's correlation coefficient. Results: FPI-6 total score showed a substantial inter-rater (Kw = .66) and test-retest reliability (Kw = .72). The six items of FPI-6 demonstrated inter-rater and test-retest reliability varying from fair to substantial (Kw = .33 to .76 and Kw = .40 to .78, respectively). Bland-Altman plots and respective 95% LOA indicated that there appeared no systematic bias and the acceptable agreement of FPI-6 total score for inter-rater and test-retest was excellent. There was a statistically significant positive correlation between each item and the total score of FPI-6, which indicated that FPI-6 had good internal consistency. Conclusion: In conclusion, the reliability of FPI-6 total score and the six items of FPI-6 were fair to substantial. The results can provide a reliable way for clinicians and researchers to implement the assessment of foot posture in patients with KOA.

The role of tripartite motif-containing 28 in cancer progression and its therapeutic potentials.

Tripartite motif-containing 28 (TRIM28) belongs to tripartite motif (TRIM) family. TRIM28 not only binds and degrades its downstream target, but also acts as a transcription co-factor to inhibit gene expression. More and more studies have shown that TRIM28 plays a vital role in tumor genesis and progression. Here, we reviewed the role of TRIM28 in tumor proliferation, migration, invasion and cell death. Moreover, we also summarized the important role of TRIM28 in tumor stemness sustainability and immune regulation. Because of the importance of TRIM28 in tumors, TIRM28 may be a candidate target for anti-tumor therapy and play an important role in tumor diagnosis and treatment in the future.

Rac1 promotes the reprogramming of glucose metabolism and the growth of colon cancer cells through upregulating SOX9.

Metabolic reprogramming is the survival rule of tumor cells, and tumor cells can meet their high metabolic requirements by changing the energy metabolism mode. Metabolic reprogramming of tumor cells is an important biochemical basis of tumor malignant phenotypes. Ras-related C3 botulinum toxin substrate 1 (Rac1) is abnormally expressed in a variety of tumors and plays an important role in the proliferation, invasion, and migration of tumor cells. However, the role of Rac1 in tumor metabolic reprogramming is still unclear. Herein, we revealed that Rac1 was highly expressed in colon cancer tissues and cell lines. Rac1 promotes the proliferation, migration, and invasion of colon cancer cells by upregulating SOX9, which as a transcription factor can directly bind to the promoters of HK2 and G6PD genes and regulate their transcriptional activity. Rac1 upregulates the expression of SOX9 through the PI3K/AKT signaling pathway. Moreover, Rac1 can promote glycolysis and the activation of the pentose phosphate pathway in colon cancer cells by mediating the axis of SOX9/HK2/G6PD. These findings reveal novel regulatory axes involving Rac1/SOX9/HK2/G6PD in the development and progression of colon cancer, providing novel promising therapeutic targets.

Asymmetries and relationships between muscle strength, proprioception, biomechanics, and postural stability in patients with unilateral knee osteoarthritis.

Background: The pathological mechanism of knee osteoarthritis (KOA) is unknown. KOA degeneration may be associated with changes in muscle strength, proprioception, biomechanics, and postural stability. Objective: This study aimed to assess asymmetries in muscle strength, proprioception, biomechanics, and postural stability of bilateral lower limbs in patients with unilateral KOA and healthy controls and analyze correlations between KOA and these parameters. Methods: A total of 50 patients with unilateral KOA (age range: 50-70) and 50 healthy subjects were recruited as study participants (age range: 50-70). Muscle strength, proprioception, femorotibial angle (FTA), femoral condylar-tibial plateau angle (FCTP), average trajectory error (ATE), and center of pressure (COP) sways areas were accessed in study participants, and the correlation between these variables was investigated. Results: In patients with unilateral KOA, lower limb muscle strength was significantly lower on the symptomatic side than on the asymptomatic side (p < 0.01), while the proprioception (degree error), FTA, FCTP, and ATE were substantially higher compared to the asymptomatic side (p < 0.01). However, no significant difference was observed in the healthy controls (p > 0.05). Patients with unilateral KOA had lower muscle strength than healthy controls (p < 0.05), but their proprioception (degree error: the difference between the target and reproduction angles), ATE, and COP sway areas were higher (p < 0.05). Muscle strength was found to be negatively correlated with ATE and COP sways areas (p < 0.05), whereas proprioception (degree error) was positively correlated with ATE and COP sways areas (p < 0.05) in all study participants. However, no correlation was found between FTA, FCTP, and ATE, COP sways areas in patients with unilateral KOA (p > 0.05). Conclusion: In patients with unilateral KOA, muscle strength, proprioception, biomechanics, and postural stability of bilateral limbs are asymmetrical in unilateral KOA patients. Muscle strength, proprioception, and postural stability are significantly associated variables, and changes in these variables should be considered in KOA prevention and rehabilitation.

Preoperative Strength Training for Clinical Outcomes Before and After Total Knee Arthroplasty: A Systematic Review and Meta-Analysis.

Background: There is an increasing interest in preoperative strength training for promoting post-operative rehabilitation, but the effectiveness of preoperative strength training for clinical outcomes after total knee arthroplasty (TKA) remains controversial. Objective: This study aims to systematically evaluate the effect of preoperative strength training on clinical outcomes before and after TKA. Methods: We systematically searched PubMed, Cochrane Library, Web of Science, and EMBASE databases from the inception to November 17, 2021. The meta-analysis was performed to evaluate the effects of preoperative strength training on clinical outcomes before and after TKA. Results: Seven randomized controlled trials (RCTs) were included (n = 306). Immediately before TKA, the pooled results showed significant improvements in pain, knee function, functional ability, stiffness, and physical function in the strength training group compared with the control group, but not in strength (quadriceps), ROM, and WOMAC (total). Compared with the control group, the results indicated strength training had a statistically significant improvement in post-operative knee function, ROM, and functional ability at less than 1 month and 3 months, and had a statistically significant improvement in post-operative strength (quadriceps), stiffness, and WOMAC (total) at 3 months, and had a statistically significant improvement in post-operative pain at 6 months. However, the results indicated strength training had no statistically significant improvement in post-operative strength (quadriceps) at less than 1 month, 6, and 12 months, had no statistically significant improvement in post-operative pain at less than 1 month, 3, and 12 months, had no statistically significant improvement in post-operative knee function at 6 and 12 months, and had no statistically significant improvement in post-operative physical function at 3 months. Conclusions: Preoperative strength training may be beneficial to early rehabilitation after TKA, but the long-term efficacy needs to be further determined. At the same time, more caution should be exercised when interpreting the clinical efficacy of preoperative strength training for TKA.

Customized Design 3D Printed PLGA/Calcium Sulfate Scaffold Enhances Mechanical and Biological Properties for Bone Regeneration.

Polylactic glycolic acid copolymer (PLGA) has been widely used in tissue engineering due to its good biocompatibility and degradation properties. However, the mismatched mechanical and unsatisfactory biological properties of PLGA limit further application in bone tissue engineering. Calcium sulfate (CaSO4) is one of the most promising bone repair materials due to its non-immunogenicity, well biocompatibility, and excellent bone conductivity. In this study, aiming at the shortcomings of activity-lack and low mechanical of PLGA in bone tissue engineering, customized-designed 3D porous PLGA/CaSO4 scaffolds were prepared by 3D printing. We first studied the physical properties of PLGA/CaSO4 scaffolds and the results showed that CaSO4 improved the mechanical properties of PLGA scaffolds. In vitro experiments showed that PLGA/CaSO4 scaffold exhibited good biocompatibility. Moreover, the addition of CaSO4 could significantly improve the migration and osteogenic differentiation of MC3T3-E1 cells in the PLGA/CaSO4 scaffolds, and the PLGA/CaSO4 scaffolds made with 20 wt.% CaSO4 exhibited the best osteogenesis properties. Therefore, calcium sulfate was added to PLGA could lead to customized 3D printed scaffolds for enhanced mechanical properties and biological properties. The customized 3D-printed PLGA/CaSO4 scaffold shows great potential for precisely repairing irregular load-bearing bone defects.

Beta-tricalcium phosphate enhanced mechanical and biological properties of 3D-printed polyhydroxyalkanoates scaffold for bone tissue engineering.

Polyhydroxyalkanoates (PHA) is a naturally degradable polyester with good biocompatibility. However, several disadvantages including poor bioactivity and mechanical properties limit the biomedical application of PHA. To circumvent these drawbacks, PHA needs to be blended with other materials to improve performance. Beta-tricalcium phosphate (ß-TCP) has emerged as one of the most promising bone repair materials due to its good biocompatibility, satisfactory mechanical properties, and excellent bone osteoconductivity. In this study, PHA filled with ß-TCP in 0 wt%, 5 wt%, 10 wt%, 20 wt%, and 30 wt% of concentrations were produced using a twin-screw extruder. The extruded 3D filaments made with 20% ß-TCP exhibited the maximum mechanical properties to manufacture 3D scaffolds for bone tissue engineering. We then prepared the 3D-printed PHA/ß-TCP scaffolds by using the fused deposition modeling (FDM) technique. The compressive strength and the shore hardness of the PHA/20%ß-TCP scaffold were 36.7 MPa and 81.1 HD. The produced scaffolds presented compressive strength compatible with natural bone. In addition, the scaffolds with a well-controlled design of pore shape and size provided sufficient space for cellular activity. In vitro studies demonstrated that the addition of ß-TCP could significantly improve the proliferation, adhesion, and migration of MC3T3-E1 cells in the PHA/ß-TCP scaffold. Moreover, the osteogenesis-related genes expression of the PHA/ß-TCP scaffold was enhanced compared to the PHA scaffolds. Therefore, the 3D-printed PHA/ß-TCP scaffold represents an effective strategy to promote mechanical and biological properties, showing huge potential for bone tissue engineering applications.