Injectable cross-linked hyaluronic acid hydrogels with epigallocatechin gallate loading as vitreous substitutes.

Hyaluronic acid (HA) serves as a vitreous substitute owing to its ability to mimic the physical functions of native vitreous humor. However, pure HA hydrogels alone do not provide sufficient protection against potential inflammatory risks following vitrectomy. In this study, HA was crosslinked with 1,4-butanediol diglycidyl ether (BDDE) to form HA hydrogels (HB). Subsequently, the anti-inflammatory agent epigallocatechin gallate (EGCG) was added to the hydrogel (HBE) for ophthalmic applications as a vitreous substitute. The characterization results indicated the successful preparation of HB with transparency, refractive index, and osmolality similar to those of native vitreous humor, and with good injectability. The anti-inflammatory ability of HBE was also confirmed by the reduced expression of inflammatory genes in retinal pigment epithelial cells treated with HBE compared with those treated with HB. In a New Zealand white rabbit model undergoing vitreous substitution treatment, HBE 50 (EGCG 50 µM addition) exhibited positive results at 28 days post-surgery. These outcomes included restored intraocular pressure, improved electroretinogram responses, minimal increase in corneal thickness, and no inflammation during histological examination. This study demonstrated the potential of an injectable HA-BDDE cross-linked hydrogel containing EGCG as a vitreous substitute for vitrectomy applications, offering prolonged degradation time and anti-inflammatory effects postoperatively.

Novel artificial tricalcium phosphate and magnesium composite graft facilitates angiogenesis in bone healing.

BACKGROUND: Bone grafting is the standard treatment for critical bone defects, but autologous grafts have limitations like donor site morbidity and limited availability, while commercial artificial grafts may have poor integration with surrounding bone tissue, leading to delayed healing. Magnesium deficiency negatively impacts angiogenesis and bone repair. Therefore, incorporating magnesium into a synthetic biomaterial could provide an excellent bone substitute. This study aims to evaluate the morphological, mechanical, and biological properties of a calcium phosphate cement (CPC) sponge composed of tetracalcium phosphate (TTCP) and monocalcium phosphate monohydrate (MCPM), which could serve as an excellent bone substitute by incorporating magnesium. METHODS: This study aims to develop biomedical materials composed mainly of TTCP and MCPM powder, magnesium powder, and collagen. The materials were prepared using a wet-stirred mill and freeze-dryer methods. The particle size, composition, and microstructure of the materials were investigated. Finally, the biological properties of these materials, including 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay for biocompatibility, effects on bone cell differentiation by alkaline phosphatase (ALP) activity assay and tartrate-resistant acid phosphatase (TRAP) activity assay, and endothelial cell tube formation assay for angiogenesis, were evaluated as well. RESULTS: The data showed that the sub-micron CPC powder, composed of TTCP/MCPM in a 3.5:1 ratio, had a setting time shorter than 15 minutes and a compressive strength of 4.39±0.96 MPa. This reveals that the sub-micron CPC powder had an adequate setting time and mechanical strength. We found that the sub-micron CPC sponge containing magnesium had better biocompatibility, including increased proliferation and osteogenic induction effects without cytotoxicity. The CPC sponge containing magnesium also promoted angiogenesis. CONCLUSION: In summary, we introduced a novel CPC sponge, which had a similar property to human bone promoted the biological functions of bone cells, and could serve as a promising material used in bone regeneration for critical bone defects.

Bletilla striata Polysaccharide-Containing Carboxymethyl Cellulose Bilayer Structure Membrane for Prevention of Postoperative Adhesion and Achilles Tendon Repair.

Postoperative tissue adhesion and poor tendon healing are major clinical problems associated with tendon surgery. To avoid postoperative adhesion and promote tendon healing, we developed and synthesized a membrane to wrap the surgical site after tendon suturing. The bilayer-structured porous membrane comprised an outer layer [1,4-butanediol diglycidyl ether cross-linked with carboxymethyl cellulose (CX)] and an inner layer [1,4-butanediol diglycidyl ether cross-linked with Bletilla striata polysaccharides and carboxymethyl cellulose (CXB)]. The morphology, chemical functional groups, and membrane structure were determined. In vitro experiments revealed that the CX/CXB membrane demonstrated good biosafety and biodegradability, promoted tenocyte proliferation and migration, and exhibited low cell attachment and anti-inflammatory effects. Furthermore, in in vivo animal study, the CX/CXB membrane effectively reduced postoperative tendon-peripheral tissue adhesion and improved tendon repair, downregulating inflammatory cytokines in the tendon tissue at the surgical site, which ultimately increased tendon strength by 54% after 4 weeks.

Development of a Machine Learning Algorithm to Correlate Lumbar Disc Height on X-rays with Disc Bulging or Herniation.

Lumbar disc bulging or herniation (LDBH) is one of the major causes of spinal stenosis and related nerve compression, and its severity is the major determinant for spine surgery. MRI of the spine is the most important diagnostic tool for evaluating the need for surgical intervention in patients with LDBH. However, MRI utilization is limited by its low accessibility. Spinal X-rays can rapidly provide information on the bony structure of the patient. Our study aimed to identify the factors associated with LDBH, including disc height, and establish a clinical diagnostic tool to support its diagnosis based on lumbar X-ray findings. In this study, a total of 458 patients were used for analysis and 13 clinical and imaging variables were collected. Five machine-learning (ML) methods, including LASSO regression, MARS, decision tree, random forest, and extreme gradient boosting, were applied and integrated to identify important variables for predicting LDBH from lumbar spine X-rays. The results showed L4-5 posterior disc height, age, and L1-2 anterior disc height to be the top predictors, and a decision tree algorithm was constructed to support clinical decision-making. Our study highlights the potential of ML-based decision tools for surgeons and emphasizes the importance of L1-2 disc height in relation to LDBH. Future research will expand on these findings to develop a more comprehensive decision-supporting model.

Nanoscaled biphasic calcium phosphate modulates osteogenesis and attenuates LPS-induced inflammation.

Micron-scale structure biphasic calcium phosphate (BCP) materials have demonstrated promising clinical outcomes in the field of bone tissue repair. However, research on biphasic calcium phosphate materials at the nanoscale level remains limited. In this study, we synthesize granular-shaped biphasic calcium phosphate nanomaterials with multiple desirable characteristics, including negatively charged surfaces, non-cytotoxicity, and the capability to penetrate cells, using a nanogrinding dispersion process with a polymeric carboxylic acid as the dispersant. Our results reveal that treating human osteoblasts with 0.5 µg/mL biphasic calcium phosphate nanomaterials results in a marked increase in alkaline phosphatase (ALP) activity and the upregulation of osteogenesis-related genes. Furthermore, these biphasic calcium phosphate nanomaterials exhibit immunomodulatory properties. Treatment of THP-1-derived macrophages with BCP nanomaterials decreases the expression of various inflammatory genes. Biphasic calcium phosphate nanomaterials also mitigate the elevated inflammatory gene expression and protein production triggered by lipopolysaccharide (LPS) exposure in THP-1-derived macrophages. Notably, we observe that biphasic calcium phosphate nanomaterials have the capacity to reverse the detrimental effects of LPS-stimulated macrophage-conditioned medium on osteoblastic activity and mineralization. These findings underscore the potential utility of biphasic calcium phosphate nanomaterials in clinical settings for the repair and regeneration of bone tissue. In conclusion, this study highlights the material properties and positive effects of biphasic calcium phosphate nanomaterials on osteogenesis and immune regulation, opening a promising avenue for further research on inflammatory osteolysis in patients undergoing clinical surgery.

Controlled release of Clenbuterol from a hydroxyapatite carrier for the treatment of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease is a neurodegenerative disorder, and Aß aggregation is considered to be the central process implicated in its pathogenesis. Current treatments are faced by challenges such as serious side effects and reduced drug bioavailability. In this study, we developed a drug delivery system for intramuscular injection that uses cellular activity to achieve constant and long-term drug release. METHODS: Synthesized mesoporous hydroxyapatite (SHAP) was prepared via co-precipitation, and hydrophobic surface modification using stearic acid was then used to load clenbuterol by physical absorption, thus creating the drug delivery system. Clenbuterol release was achieved through cellular activity, with macrophage uptake triggering lysosome/endosome disruption, cytoplasmic release, extracellular exocytosis, and subsequent systemic circulation. RESULTS: We found that clenbuterol-loaded SHAP enabled sustained release for more than 2 weeks and effectively modulated inflammation, reduced Aß oligomer-induced toxicity, and prevented Aß aggregation. CONCLUSIONS: Our findings suggest that treatment with clenbuterol loaded in this SHAP delivery system could be a promising strategy for treating Alzheimer's disease.

Biobased chitosan-derived self-nitrogen-doped porous carbon nanofibers containing nitrogen-doped zeolites for efficient removal of uremic toxins during hemodialysis.

Highly efficient adsorbents are needed to remove uremic toxins and reduce the economic and societal burden of the current dialysis treatments in resource-limited environments. In this study, nanostructured porous carbon nanofibers with nitrogen-doped zeolites (NZ-PCNF) were prepared, by electrospinning zeolites with chitosan-poly(ethylene oxide) blends, followed by a one-step carbonization process, without further activation steps or aggressive chemical additives for N-doping. The results showed that N-zeolites were successfully integrated into an ultrafine carbon nanofiber network, with a uniform nanofiber diameter of approximately 25 nm, hierarchical porous structure (micro- and mesopores), and high specific surface area (639.29 m2/g), facilitating uremic toxin diffusion and adsorption. The self-N-doped structure in the NZ-PCNF removed more creatinine (∼1.8 times) than the porous carbon nanofibers when using the same weight of precursor materials. Cytotoxicity and hemolysis tests were performed to verify the safety of NZ-PCNF. This study provides a novel strategy for transforming chitosan-based materials into state-of-the-art porous carbon nanofiber/zeolite self-N-doped composites, affording an efficient bioderived adsorbent for the removal of uremic toxins in patients with chronic kidney disease.

The synthesis and evaluation of thiolated alginate as the barrier to block nutrient absorption on small intestine for body-weight control.

Obesity is the most common health concern all over the world. However, till now, there is no promising way to manage obesity or body-weight control. The aim of the study is to develop an edible gel as a health supplement that temporarily attaches to the mucus of the intestines, forming an absorption barrier to block the nutrients. We modify the alginate with the thiol group as thiolated alginate (TA) that may stay on the mucosa layer for a much longer time to reduce nutrient absorption. In this study, the TA is synthesized successfully and proved a good mucosal adhesion to serve as a barrier for nutrient absorption both in vitro and in vivo. The results of in vivo imaging system (IVIS) show that the synthesized TA can be exiled from the gastrointestinal tract within 24 h. The animal study shows that the TA by daily oral administration can effectively reduce body weight and fat deposition. The biosafety is evaluated in vitro at the cellular level, based on ISO-10993, and further checked by animal study. We do believe that the TA could have a greater potential to be developed into a safe health supplement to manage obesity and for body-weight control.

The combination of resveratrol and Bletilla striata polysaccharide decreases inflammatory markers of early osteoarthritis knee and the preliminary results on LPS-induced OA rats.

Osteoarthritis (OA) of the knee is characterized by progressive deterioration and loss of articular cartilage with associatedstructural and performance changes in the entire joint, and current treatments for OA only aim to relieve symptoms, rather than to prevent or reverse disease progression. Recently, treatments targeting "early osteoarthritis" (EOA) have attracted attention. However, during EOA stage, chondrocytes may change behaviors to express pro-inflammatory cytokines and free radicals, which would cause detrimental effects to the synovial cavity and further cartilage wear. In this study, we combined resveratrol (Res) and Bletilla striata polysaccharide (BSP) as anti-inflammatories and antioxidants to diffuse free radicals and to alleviate inflammation from the synovial cavity both short term and long term. The current study introduced a new method for harvesting BSP from as-received Bletilla striata to achieve high yields, shortened extraction times, and maintained structure/functions. In addition, it combined Res and home-extracted BSP (Res-BSP) to alleviate oxidative stress and inflammation in a Lipopolysaccharide (LPS)-induced OA model. The gene expressions of inflammatory genes iNOs, IL-1ß, IL-6, and MMP-13 were upregulated 5.7-fold, 6.5-fold, 8.6-fold, and 4.5-fold, respectively on OA-like chondrocytes and the gene expressions were significantly downregulated to 3.3-fold, 2.1-fold, 4.9-fold, and 0.1-fold, respectively, once OA-like chondrocytes were treated with Res-BSP (p < 0.05, compared with OA-like chondrocytes). The gene expressions of chondrogenic genes TGFß1, SOX9, and type II collagen were downregulated by 0.8-fold, 2.2-fold, and 0.8-fold, respectively, based on the control group as a baseline. While it was significantly upregulated by 3.4-fold, 0.32-fold, and 0.4-fold, respectively, once OA-like chondrocytes were treated with Res-BSP. (p < 0.05, compared with OA-like chondrocytes). Finally, we elucidated the role of Res-BSP in EOA in suppressing COX-2 and activating p-Smad 2/3 and p-Erk1/2. We believe that the combination of Res and BSP has great potential as an alternative therapeutic strategy for EOA treatment in future.

Current Role and Potential of Polymeric Biomaterials in Clinical Obesity Treatment.

The rise of obesity and associated fatal diseases has taken a massive toll worldwide. Despite the existing pharmaceuticals and bariatric surgeries, these approaches manifest limited efficacy or accompany various side effects. Therefore, researchers seek to facilitate the prolonged and specific delivery of therapeutics. Or else, to mimic the essential part of "gastric bypass" by physically blocking excessive absorption via less invasive methods. To achieve these goals, polymeric biomaterials have gained tremendous interest recently. They are known for synthesizing hydrogels, microneedle patches, mucoadhesive coatings, polymer conjugates, and so forth. In this Review, we provide insights into the current studies of polymeric biomaterials in the prevention and treatment of obesity, inspiring future improvements in this regime of study.

Porous hydroxyapatite carrier enables localized and sustained delivery of honokiol for glioma treatment.

The objective of this study is to develop hydroxyapatite (HAp) particles for targeted delivery of honokiol to tumor sites after glioma surgical management. Honokiol is released from the HAp-honokiol particles inside cancer cells through endocytosis and subsequent acid lysosomal dissolution. HAp is synthesized using a co-precipitation method, and egg white is added to create porous structures. The HAp is then surface-modified with stearic acid to enhance its hydrophobicity and loaded with honokiol to form HAp-honokiol particles. The synthesized particles are of appropriate size and characteristics for cancer cell uptake. Honokiol remains attached on to the HAp particles in neutral environments due to its hydrophobic nature, but undergoes rapid burst release in acidic environments such as lysosomes. The HAp-honokiol treatment shows a delayed effect on cell viability and cytotoxicity, indicating sustained drug release without compromising drug efficacy. Flow cytometry analysis demonstrates the apoptosis pathway induced by HAp-honokiol in ALTS1C1 glioma cells. In the in vivo study using a mouse glioma model, MRI results showed a 40% reduction in tumor size after HAp-honokiol treatment. These findings suggest that HAp-honokiol particles have potential as an effective drug delivery system for the treatment of glioma.

Through Its Powerful Antioxidative Properties, L-Theanine Ameliorates Vincristine-Induced Neuropathy in Rats.

L-theanine (LT), which is a major amino acid found in green tea, was shown to alleviate Vincristine (VCR)-induced peripheral neuropathy and associated neuronal functional changes in rats. To induce peripheral neuropathy, rats were administered VCR at a dose of 100 mg/kg/day intraperitoneally on days 1-5 and 8-12, while control rats received LT at doses of 30, 100, and 300 mg/kg/day intraperitoneally for 21 days or saline solution. Electrophysiological measurements were taken to evaluate the nerve functional loss and recovery through motor and sensory nerve conduction velocities. The sciatic nerve was examined for several biomarkers, including nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), total calcium, IL-6, IL-10, MPO, and caspase-3. The results showed that VCR caused significant hyperalgesia and allodynia in rats; decreased nerve conduction velocity; increased NO and MDA levels; and decreased GSH, SOD, CAT, and IL-10 levels. LT was found to significantly reduce VCR-induced nociceptive pain thresholds, decrease oxidative stress levels (NO, MDA), increase antioxidative strength (GSH, SOD, CAT), and reduce neuroinflammatory activity and apoptosis markers (caspase-3). LT's antioxidant, calcium homeostasis, anti-inflammatory, anti-apoptotic, and neuroprotective properties make it a potential adjuvant to conventional treatment in VCR-induced neuropathy in rats.

Aligned core-shell fibrous nerve wrap containing Bletilla striata polysaccharide improves functional outcomes of peripheral nerve repair.

Peripheral nerve injuries are commonly encountered in extremity traumas. Their motor and sensory recovery following microsurgical repair is limited by slow regeneration speed (<1 mm/d) and subsequent muscle atrophy, which are consequently correlated with the activity of local Schwann cells and efficacy of axon outgrowth. To promote post-surgical nerve regeneration, we synthesized a nerve wrap consisting of an aligned polycaprolactone (PCL) fiber shell with a Bletilla striata polysaccharide (BSP) core (APB). Cell experiments demonstrated that the APB nerve wrap markedly promoted neurite outgrowth and Schwann cell migration and proliferation. Animal experiments applying a rat sciatic nerve repair model indicated that the APB nerve wrap restored conduction efficacy of the repaired nerve and the compound action potential as well as contraction force of the related leg muscles. Histology of the downstream nerves disclosed significantly higher fascicle diameter and myelin thickness with the APB nerve wrap compared to those without BSP. Thus, the BSP-loaded nerve wrap is potentially beneficial for the functional recovery after peripheral nerve repair and offers sustained targeted release of a natural polysaccharide with good bioactivity.

3D-Cultured Adipose-Derived Stem Cell Spheres Using Calcium-Alginate Scaffolds for Osteoarthritis Treatment in a Mono-Iodoacetate-Induced Rat Model.

Osteoarthritis (OA) is a degenerative disease that causes pain, cartilage deformation, and joint inflammation. Mesenchymal stem cells (MSCs) are potential therapeutic agents for OA treatment. However, the 2D culture of MSCs could potentially affect their characteristics and functionality. In this study, calcium-alginate (Ca-Ag) scaffolds were prepared for human adipose-derived stem cell (hADSC) proliferation with a homemade functionally closed process bioreactor system; the feasibility of cultured hADSC spheres in heterologous stem cell therapy for OA treatment was then evaluated. hADSC spheres were collected from Ca-Ag scaffolds by removing calcium ions via ethylenediaminetetraacetic acid (EDTA) chelation. In this study, 2D-cultured individual hADSCs or hADSC spheres were evaluated for treatment efficacy in a monosodium iodoacetate (MIA)-induced OA rat model. The results of gait analysis and histological sectioning showed that hADSC spheres were more effective at relieving arthritis degeneration. The results of serological and blood element analyses of hADSC-treated rats indicated that the hADSC spheres were a safe treatment in vivo. This study demonstrates that hADSC spheres are a promising treatment for OA and can be applied to other stem cell therapies or regenerative medical treatments.

Fluoxetine Inhibits STAT3-mediated Survival and Invasion of Osteosarcoma Cells.

BACKGROUND/AIM: Osteosarcoma (OS) is a common primary malignancy of bone in adolescents. Its highly metastatic characteristics can lead to treatment failure and poor prognosis. Although standard treatments, including surgery, radiotherapy, and chemotherapy, have progressed in the past decade, treatment options to overcome metastatic progression remain sparse. Fluoxetine, an anti-depressant, has been widely used in patients with cancer for their mental issues and was reported to possess antitumor potential. However, the effect of fluoxetine on OS remains unclear. MATERIALS AND METHODS: In this study, we used cell viability, invasion/migration transwell, wound-healing and aortic ring assays to identify the effects of fluoxetine on metastasis and progression in OS. RESULTS: Fluoxetine induced cytotoxicity in OS cells by activating both extrinsic/intrinsic apoptosis signaling pathways. Proliferation and anti-apoptosis-related factors such as cyclin D1 and X-linked inhibitor of apoptosis were suppressed by fluoxetine. Additionally, fluoxetine suppressed the invasive/migratory abilities of OS and inhibited the development of angiogenesis by reducing the phosphorylation of signal transducer and activator of transcription 3 (STAT3). Metastasis-associated factors, vascular endothelial growth factors, matrix metallopeptidase 2 and -9, were all reduced in OS cells by fluoxetine treatment. CONCLUSION: Fluoxetine not only induces cytotoxicity and apoptosis of OS cells, but also suppresses metastasis and angiogenesis by targeting STAT3.

Therapeutic potential of nanoceria pretreatment in preventing the development of urological chronic pelvic pain syndrome: Immunomodulation via reactive oxygen species scavenging and SerpinB2 downregulation.

Urological chronic pelvic pain syndrome (UCPPS) manifests as pelvic pain with frequent urination and has a 10% prevalence rate without effective therapy. Nanoceria (cerium oxide nanoparticles [CNPs]) were synthesized in this study to achieve potential long-term pain relief, using a commonly used UCPPS mouse model with cyclophosphamide-induced cystitis. Transcriptome sequencing analysis revealed that serpin family B member 2 (SerpinB2) was the most upregulated marker in mouse bladder, and SerpinB2 was downregulated with CNP pretreatment. The transcriptome sequencing analysis results agreed with quantitative polymerase chain reaction and western blot analysis results for the expression of related mRNAs and proteins. Analysis of Gene Expression Omnibus (GEO) datasets revealed that SerpinB2 was a differentially upregulated gene in human UCPPS. In vitro SerpinB2 knockdown downregulated proinflammatory chemokine expression (chemokine receptor CXCR3 and C-X-C motif chemokine ligand 10) upon treatment with 4-hydroperoxycyclophosphamide. In conclusion, CNP pretreatment may prevent the development of UCPPS, and reactive oxygen species (ROS) scavenging and SerpinB2 downregulation may modulate the immune response in UCPPS.

Injectable methacrylated gelatin/thiolated pectin hydrogels carrying melatonin/tideglusib-loaded core/shell PMMA/silk fibroin electrospun fibers for vital pulp regeneration.

Use of injectable hydrogels attract attention in the regeneration of dental pulp due to their ability to fill non-uniform voids such as pulp cavities. Here, gelatin methacrylate/thiolated pectin hydrogels (GelMA/PecTH) carrying electrospun core/shell fibers of melatonin (Mel)-polymethylmethacrylate (PMMA)/Tideglusib (Td)-silk fibroin (SF) were designed as an injectable hydrogel for vital pulp regeneration, through prolonged release of Td and Mel to induce proliferation and odontoblastic differentiation of dental pulp stem cells (DPSC). H NMR and FTIR confirmed methacrylation of Gel and thiolation of Pec. Addition of PMMA/SF increased degradation and water retention capacities of GelMA/PecTH. Rheological analyses and syringe tests proved the injectability of the hydrogel systems. Release studies indicated that Td and Mel were released from the fibers inside the hydrogels sequentially due to their specific locations. This release pattern from the hydrogels resulted in DPSC proliferation and odontogenic differentiation in vitro. Gene expression studies showed that the upregulation of DMP1, DSPP, and Axin-2 genes was promoted by GelMA/PecTH carrying PMMA/SF loaded with Mel (50 µg/mL) and Td (200 nM), respectively. Our results suggest that this hydrogel system holds promise for use in the regeneration of pulp tissue.

An assessment of physical properties and the viability of osteoblast-like cells of cefazolin-impregnated calcium sulfate bone-void filler.

Calcium sulfate, an injectable and biodegradable bone-void filler, is widely used in orthopedic surgery. Based on clinical experience, bone-defect substitutes can also serve as vehicles for the delivery of drugs, for example, antibiotics, to prevent or to treat infections such as osteomyelitis. However, antibiotic additions change the characteristics of calcium sulfate cement. Moreover, high-dose antibiotics may also be toxic to bony tissues. Accordingly, cefazolin at varying weight ratios was added to calcium sulfate samples and characterized in vitro. The results revealed that cefazolin changed the hydration reaction and prolonged the initial setting times of calcium sulfate bone cement. For the crystalline structure identification, X-ray diffractometer revealed that cefazolin additive resulted in the decrease of peak intensity corresponding to calcium sulfate dihydrate which implying incomplete phase conversion of calcium sulfate hemihydrate. In addition, scanning electron microscope inspection exhibited cefazolin changed the morphology and size of the crystals greatly. A relatively higher amount of cefazolin additive caused a faster degradation and a lower compressive strength of calcium sulfate compared with those of uploaded samples. Furthermore, the extract of cefazolin-impregnated calcium sulfate impaired cell viability, and caused the death of osteoblast-like cells. The results of this study revealed that the cefazolin additives prolonged setting time, impaired mechanical strength, accelerated degradation, and caused cytotoxicity of the calcium sulfate bone-void filler. The aforementioned concerns should be considered during intra-operative applications.

Bio-Based PLA/PBS/PBAT Ternary Blends with Added Nanohydroxyapatite: A Thermal, Physical, and Mechanical Study.

The physical and mechanical properties of novel bio-based polymer blends of polylactic acid (PLA), poly(butylene succinate) (PBS), and poly (butylene adipate-co-terephthalate) (PBAT) with various added amounts of nanohydroxyapatite (nHA) were investigated in this study. The formulations of PLA/PBS/PBAT/nHA blends were divided into two series, A and B, containing 70 or 80 wt% PLA, respectively. Samples of four specimens per series were prepared using a twin-screw extruder, and different amounts of nHA were added to meet the regeneration needs of bone graft materials. FTIR and XRD analyses were employed to identify the presence of each polymer and nHA in the various blends. The crystallization behavior of these blends was examined using DSC. Tensile and impact strength tests were performed on all samples to screen feasible formulations of polymer blends for bone graft material applications. Surface morphology analyses were conducted using SEM, and the dispersion of nHA particles in the blends was further tested using TEM. The added nHA also served as a nucleating agent aimed at improving the crystallinity and mechanical properties of the blends. Through the above analyses, the physical and mechanical properties of the polymer blends are reported and the most promising bone graft material formulations are suggested. All blends were tested for thermal degradation analysis using TGA and thermal stability was confirmed. The water absorption experiments carried out in this study showed that the addition of nHA could improve the hydrophilicity of the blends.

Ameliorative Effects of Cumin Extract-Encapsulated Chitosan Nanoparticles on Skeletal Muscle Atrophy and Grip Strength in Streptozotocin-Induced Diabetic Rats.

Skeletal muscle atrophy is a disorder characterized by reductions in muscle size and strength. Cumin extract (CE) possesses anti-inflammatory, antioxidant, and hypoglycemic properties. Its pharmaceutical applications are hindered by its low water solubility and by its cytotoxicity when administered at high doses. In this study, we have developed a simplified water distillation method using a rotary evaporator to isolate the active components in cumin seeds. The anti-inflammatory effects of CE and its potential to ameliorate skeletal muscle atrophy in rats with streptozotocin (STZ)-induced diabetes were evaluated. The half-maximal inhibitory concentration (IC50) of CE for cells was 80 µM. By encapsulating CE in chitosan nanoparticles (CECNs), an encapsulation efficacy of 87.1% was achieved with a slow release of 90% of CE after 24 h of culturing, resulting in CECNs with significantly reduced cytotoxicity (IC50, 1.2 mM). Both CE and CECNs significantly reduced the inflammatory response in interleukin (IL)-6 and IL-1ß assays. STZ-induced diabetic rats exhibited sustained high blood glucose levels (>16.5 mmol/L), small and damaged pancreatic ß islets, and skeletal muscle atrophy. CE and CECN treatments ameliorated skeletal muscle atrophy, recovered muscle fiber striated appearance, increased grip strength, and decreased IL-6 level. Furthermore, CE and CECNs led to a reduction of damage to the pancreas, restoring its morphological phenotype, increasing serum insulin levels, and lowering blood glucose levels in STZ-induced diabetic rats. Taken together, treatment with CECNs over a 6-week period yielded positive ameliorative effects in STZ-induced rats of muscle atrophy.