Thioxanthone-Based Siloxane Photosensitizer for Cationic/Radical Photopolymerization and Photoinduced Sol-Gel Reactions.

In this investigation, a multifunctional visible-light TX-based photosensitizer containing a siloxane moiety (TXS) was designed with a good overall yield of 54%. The addition of a siloxane moiety enabled the incorporation of a TX photosensitizer into a siloxane network by photoinduced sol-gel chemistry, thus avoiding its release. Both liquid 1H and solid-state 29Si NMR measurements undeniably confirmed the formation of photoacids resulting from the photolysis of the TXS/electron acceptor molecule (Iodonium salt), which promoted the photoinduced hydrolysis/condensation of the trimethoxysilane groups of TXS, with a high degree of condensation of its inorganic network. Notably, the laser flash photolysis, fluorescence, and electron paramagnetic resonance spin-trapping (EPR ST) experiments demonstrated that TXS could react with Iod through an electron transfer reaction through its excited states, leading to the formation of radical initiating species. Interestingly, the TXS/Iod was demonstrated to be an efficient photoinitiating system for free-radical (FRP) and cationic (CP) polymerization under LEDs@385, 405, and 455 nm. In particular, whatever the epoxy monomer mixtures used, remarkable final epoxy conversions were achieved up to 100% under air. In this latter case, we demonstrated that both the photoinduced sol-gel process (hydrolysis of trimethoxysilane groups) and the cationic photopolymerization occurred simultaneously.

Primary Ear Reconstruction Using Cadaveric Costal Cartilage.

OBJECTIVE: Allogeneic cadaveric costal cartilage is commonly used for grafts in nasal reconstruction surgery; however, limited information exists on its use in total ear reconstruction for microtia. In this case series, we describe the novel use of cadaveric cartilage for auricular framework construction in ear reconstruction and review preliminary histologic findings. METHODS: Patients requiring primary complete reconstruction of the auricle from August 2020 to December 2021 were eligible and underwent ear reconstruction using cadaveric costal cartilage. Patients were evaluated for surgical site infection, skin necrosis, cartilage resorption, and cartilage exposure during regular follow-up visits. Two cartilage samples were taken after 2 separate second-stage surgeries done 52 weeks after first-stage reconstruction. These samples were stained with hematoxylin and eosin as well as safranin-O and examined under light microscopy. RESULTS: A total of 12 ear reconstruction procedures using cadaveric costal cartilage were performed across 11 patients; 10 of 12 ears had type III microtia and 2 of 12 ears had type IV microtia. Patients ranged from 4 to 25 years old at the time of surgery, with an average age of 10.7 years. Follow-up time ranged from 1.6 to 25.4 months, with a mean follow-up time of 11.2 months. No patients experienced any visibly significant cartilage warping. Two patients experienced minor construct exposure, which were successfully salvaged. Two patients experienced surgical site infections, one lead to resorption requiring framework replacement. Preliminary histologic analysis of the 2 samples taken 1 year after implantation showed viable chondrocytes with no evidence of immunologic rejection or any local inflammation or host foreign body response. CONCLUSIONS: Cadaveric costal cartilage serves as a viable alternative to autologous cartilage and other alloplastic biomaterials for construction of auricular frameworks in primary microtia reconstruction. Resorption secondary to infection and construct exposure remain potential risks. Longer follow-up times and a larger sample size are needed for assessment of long-term efficacy.

The Effects of Autologous Fat Transfer in an In Vitro Model of Basal Joint Osteoarthritis.

PURPOSE: Basal joint osteoarthritis (OA) is a highly prevalent and debilitating condition. Recent clinical evidence suggests that autologous fat transfer (AFT) may be a promising, minimally invasive treatment for this condition. However, the mechanism of action is not fully understood. It is theorized that AFT reduces inflammation in the joint, functions to regenerate cartilage, or acts as a mechanical buffer. The purpose of this study was to better understand the underlying mechanism of AFT using an in vitro model. We hypothesize that the addition of stromal vascular fraction (SVF) cells will cause a reduction in markers of inflammation. METHODS: Articular chondrocytes were expanded in culture. Liposuction samples were collected from human subjects and processed similarly to AFT protocols to isolate SVF rich in adipose-derived stem cells. A control group was treated with standard growth media, and a positive control group (OA group) was treated with inflammatory cytokines. To mimic AFT, experimental groups received inflammatory cytokines and either a low or high dose of SVF. Expression of relevant genes was measured, including interleukin (IL)-1ß, IL-1 receptor antagonist, and matrix metalloproteinases (MMP). RESULTS: Compared to the OA group, significant decreases in IL-1ß, MMP3, and MMP13 expression on treatment day 3 were found in the high-dose SVF group, while MMP13 expression was also significantly decreased in the low-dose SVF group on day 3. CONCLUSIONS: In this study, we found that SVF treatment reduced expression of IL-1ß, MMP3, and MMP13 in an in vitro model of OA. These results suggest that an anti-inflammatory mechanism may be responsible for the clinical effects seen with AFT in the treatment of basal joint OA. CLINICAL RELEVANCE: An anti-inflammatory mechanism may be responsible for the clinical benefits seen with AFT for basal joint arthritis.

Exosome-Laden Scaffolds for Treatment of Post-Traumatic Cartilage Injury and Osteoarthritis of the Knee: A Systematic Review.

Mesenchymal stem cell (MSC)-based exosomes have garnered attention as a viable therapeutic for post-traumatic cartilage injury and osteoarthritis of the knee; however, efforts for application have been limited due to issues with variable dosing and rapid clearance in vivo. Scaffolds laden with MSC-based exosomes have recently been investigated as a solution to these issues. Here, we review in vivo studies and highlight key strengths and potential clinical uses of exosome-scaffold therapeutics for treatment of post-traumatic cartilage injury and osteoarthritis. In vivo animal studies were gathered using keywords related to the topic, revealing 466 studies after removal of duplicate papers. Inclusion and exclusion criteria were applied for abstract screening and full-text review. Thirteen relevant studies were identified for analysis and extraction. Three predominant scaffold subtypes were identified: hydrogels, acellular extracellular matrices, and hyaluronic acid. Each scaffold-exosome design showcased unique properties with relation to gross findings, tissue histology, biomechanics, and gene expression. All designs demonstrated a reduction in inflammation and induction of tissue regeneration. The results of our review show that current exosome-scaffold therapeutics demonstrate the capability to halt and even reverse the course of post-traumatic cartilage injury and osteoarthritis. While this treatment modality shows incredible promise, future research should aim to characterize long-term biocompatibility and optimize scaffold designs for human treatment.

Evaluation of the histological and biomechanical properties of poly-4-hydroxybutyrate scaffold for pelvic organ prolapse, compared with polypropylene mesh in a rabbit model.

INTRODUCTION AND HYPOTHESIS: Poly-4-hydroxybutyrate (P4HB) is a biopolymer produced by Escherichia coli K12 bacteria. P4HB is fully resorbed in vivo by 18-24 months post-implantation. The aim of this study is to evaluate P4HB in the rabbit abdomen and vagina to determine that the biomechanical and histological properties are similar to the standard polypropylene mesh. Our hypothesis is that the histological and biomechanical properties of a fully absorbable graft will be similar to a lightweight polypropylene (PP) mesh when implanted in rabbit vagina and abdomen. METHODS: Sixteen (n = 16) female New Zealand White (retired breeder) rabbits were equally divided between two time points (3 and 9 months). A total of 17 rabbits were used owing to one death secondary to suspected cardiomyopathy. P4HB scaffold and PP mesh were subcutaneously and peri-vaginally implanted into the rabbit abdomen and vagina respectively. All rabbits had both posterior and anterior vaginal implants, and half of the rabbits had four abdominal implants in addition to the vaginal implants. The abdominal implants were 4.5 cm long × 1.5 cm wide whereas the vaginal implants were 1.5 cm long × 0.5 cm wide. At 3 and 9 months, gross necropsy was performed and samples were obtained, sectioned, stained and evaluated via histological analysis. Specimens were assessed for host inflammatory response, neovascularization, elastin content, and collagen deposition/maturation. Specimens were also biomechanically evaluated via uniaxial tensile test to determine the stiffness, ultimate tensile strength and load at ultimate tensile strength of the device/tissue composite. RESULTS: No abdominal mesh exposures were noted. A comparable number of asymptomatic partial vaginal exposures were observed at 3 months (P4HB: n = 3; PP: n = 2) and 9 months (P4HB: n = 3; PP: n = 2) respectively. Histological analysis of specimens showed comparable results in the P4HB and PP groups at 3 and 9 months post-implantation. Although no acute inflammation was seen, chronic inflammation was demonstrated in all specimens. Elastic fibers were present in the 3-month vaginal PP and P4HB specimens, but were not seen again. There was an increase in type I/III collagen noted over time. Biomechanical evaluation of the vaginal mesh tissue complex showed ultimate tensile strength was not significantly different between P4HB and PP groups at 3 (P = 0.625) and 9 months (P = 0.250) respectively. CONCLUSIONS: P4HB scaffold may represent a fully absorbable alternative to permanent mesh for pelvic organ prolapse (POP) repair.

Biomechanical properties of the ex vivo porcine trachea: A benchmark for three-dimensional bioprinted airway replacements.

PURPOSE: Combining tissue engineering and three-dimensional (3D) printing may allow for the introduction of a living functional tracheal replacement graft. However, defining the biomechanical properties of the native trachea is a key prerequisite to clinical translation. To achieve this, we set out to define the rotation, axial stretch capacity, and positive intraluminal pressure capabilities for ex vivo porcine tracheas. STUDY DESIGN: Animal study. MATERIALS AND METHODS: Six full-length ex vivo porcine tracheas were bisected into 5.5 cm segments. Maximal positive intraluminal pressure was measured by sealing segment ends with custom designed 3D printed caps through which a pressure transducer was introduced. Axial stretch capacity and rotation were evaluated by stretching and rotating the segments along their axis between two clamps, respectively. RESULTS: Six segments were tested for axial lengthening and the average post-stretch length percentage was 148.92% (range 136.81-163.48%, 95% CI 153-143%). The mean amount of length gain achieved per cartilaginous ring was 7.82% (range 4.71-10.95%, 95% CI 6.3-9.35%). Four tracheal segments were tested for maximal positive intraluminal pressure, which was over 400 mmHg. Degree of rotation testing found that the tracheal segments easily transformed 180° in anterior-posterior bending, lateral bending, and axial rotational twisting. CONCLUSIONS: We define several biomechanical properties of the ex vivo porcine trachea by reporting the rotation, axial stretch capacity, and positive intraluminal pressure capabilities. We hope that this will aid future work in the clinical translation of 3D bioprinted airway replacement grafts and ensure their compatibility with native tracheal properties.

Drugs Loaded into Electrospun Polymeric Nanofibers for Delivery.

The electrospinning technique is a useful and versatile approach for conversion of polymeric solutions into continuous fibers, ranging from a few micrometers (10-100 µm) to the scale of nanometers (10- 100 nm) in diameters. This technique can be used in a vast number of polymers, in some cases after modifying them to the required properties. The high surface-to-volume ratio of the fibers can improve some processes like cell binding and proliferation, drug loading, and mass transfer processes. One of the most important and studied areas of electrospinning is in the drug delivery field, for the controlled release of active substances ranging from antibiotics and anticancer agents, to macromolecules such as proteins and DNA. The advantage of this method is that a wide variety of low solubility drugs can be loaded into the fibers to improve their bioavailability or to attain controlled release. This review presents an overview of the reported drugs loaded into electrospun polymeric nanofibers to be used as drug delivery systems. These drugs are classified by their applications in pharmacy.

Synergistic actions of mixed small and large pores for capillary absorption through biporous polymeric materials.

Water absorption in porous media is an important process involved in numerous materials for various applications, such as in the building industry, food processing and bioengineering. Designing new materials with appropriate absorption properties requires an understanding of how absorption behavior depends on both the material's morphology and the properties of the solid matrix, i.e. hydrophilic/hydrophobic nature and swelling/deformation properties. Although the basic principles of imbibition are well-known for simple porous systems, much less is known about absorption in complex porous systems, in particular those containing several coexisting porous phases, such as wood for example. Here, water absorption is studied for model porous organic materials exhibiting several degrees of hydrophobicity and two pore size levels, either as monoporous materials (large or small pores) or as biporous materials (mixed large and small pores). The interconnected biporous structure is designed via a double porogen templating approach using cubic sodium chloride particles as templates for the generation of the larger pore size (250-400 µm) and i-PrOH as a porogenic solvent for the smaller pore size (2-5 µm). While absorption for the small pore material is well described by the classical Washburn theory, the large pore material shows a drastic reduction in the imbibition rate. This behavior is attributed to the slow breakthrough mechanism for the water interface at sharp edge connections between pores. Remarkably, this slow regime is suppressed for the biporous material and the imbibition rate is even higher than the sum of rates obtained for its monoporous counterparts, which highlights the synergistic action of mixed small and large pores.

A pilot cadaveric study of temperature and adjacent tissue changes after exposure of magnetic-controlled growing rods to MRI.

PURPOSE: To test for possible thermal injury and tissue damage caused by magnetic-controlled growing rods (MCGRs) during MRI scans. METHODS: Three fresh frozen cadavers were utilized. Four MRI scans were performed: baseline, after spinal hardware implantation, and twice after MCGR implantation. Cross connectors were placed at the proximal end and at the distal end of the construct, making a complete circuit hinged at those two points. Three points were identified as potential sites for significant heating: adjacent to the proximal and distal cross connectors and adjacent to the actuators. Data collected included tissue temperatures at baseline (R1), after screw insertion (R2), and twice after rod insertions (R3 and R4). Tissue samples were taken and stained for signs of heat damage. RESULTS: There was a slight change in tissue temperature in the regions next to the implants between baseline and after each scan. Average temperatures (°C) increased by 0.94 (0.16-1.63) between R1 and R2, 1.6 (1.23-1.97) between R2 and R3, and 0.39 (0.03-0.83) between R3 and R4. Subsequent histological analysis revealed no signs of heat induced damage. CONCLUSION: Recurrent MRI scans of patients with MCGRs may be necessary over the course of treatment. When implanted into human cadaveric tissue, these rods appear to not be a risk to the patient with respect to heating or tissue damage. Further in vivo study is warranted. LEVEL OF EVIDENCE: N/A.

Sonographic evaluation of knee cartilage defects implanted with preconditioned scaffolds.

OBJECTIVES: The purpose of this study was to develop a novel method for creating an acellular bioactive scaffold, to prove its efficacy in vivo and in vitro for the augmentation of biological repair, and to confirm that sonographic microscopy is a viable modality for monitoring the healing process of osteochondral defects implanted with preconditioned bioactive scaffolds. METHODS: Rabbit marrow stromal cells were retrovirally transduced with either bone morphogenetic protein 7 (BMP-7) or insulinlike growth factor 1 (IGF-1) genes, cultured for 9 weeks in nonwoven poly-L-lactic acid scaffolds, and then frozen and lyophilized. The knees were evaluated at 3, 6, and 12 weeks after surgery using 20-MHz ultrasound and then prepared for routine histologic analysis. B-scans of the extracellular matrix defects were compared to histologic results. RESULTS: Control defects showed a void or a mixture of fibrocartilage tissue. Both types of scaffolds resulted in a higher percentage (both P< .001) of primarily hyaline cartilage tissue with intact articular surfaces. The osteochondral defects were clearly observed in each sonographic signature. There were no differences between images of scaffolds treated with IGF-1 or BMP-7. Extracellular matrix regrowth was found to closely parallel (R(2) = 0.968; P < .003) the histologic images. A 3-mm defect depth and a 2.5-mm scaffold thickness were measured on the sonograms, comparing well to actual dimensions. CONCLUSIONS: There was a gradual increase in healing bordering the defects for the 3-, 6-, and 12-week samples. Also, we have shown that sonography can aid in monitoring implantation of preconditioned scaffolds in osteochondral defects and thus assessing the healing process and cartilage/bone quality.

From design of bio-based biocomposite electrospun scaffolds to osteogenic differentiation of human mesenchymal stromal cells.

Electrospinning coupled with electrospraying provides a straightforward and robust route toward promising electrospun biocomposite scaffolds for bone tissue engineering. In this comparative investigation, four types of poly(3-hydroxybutyrate) (PHB)-based nanofibrous scaffolds were produced by electrospinning a PHB solution, a PHB/gelatin (GEL) mixture or a PHB/GEL/nHAs (hydroxyapatite nanoparticles) mixed solution, and by electrospinning a PHB/GEL solution and electrospraying a nHA dispersion simultaneously. SEM and TEM analyses demonstrated that the electrospun nHA-blended framework contained a majority of nHAs trapped within the constitutive fibers, whereas the electrospinning-electrospraying combination afforded fibers with a rough surface largely covered by the bioceramic. Structural and morphological characterizations were completed by FTIR, mercury intrusion porosimetry, and contact angle measurements. Furthermore, an in vitro investigation of human mesenchymal stromal cell (hMSC) adhesion and proliferation properties showed a faster cell development on gelatin-containing scaffolds. More interestingly, a long-term investigation of hMSC osteoblastic differentiation over 21 days indicate that hMSCs seeded onto the nHA-sprayed scaffold developed a significantly higher level of alkaline phosphatase activity, as well as a higher matrix biomineralization rate through the staining of the generated calcium deposits: the fiber surface deposition of nHAs by electrospraying enabled their direct exposure to hMSCs for an efficient transmission of the bioceramic osteoinductive and osteoconductive properties, producing a suitable biocomposite scaffold for bone tissue regeneration.

Design of Collagen and Gelatin-based Electrospun Fibers for Biomedical Purposes: An Overview.

Collagen and gelatin are essential natural biopolymers commonly utilized in biomaterials and tissue engineering because of their excellent physicochemical and biocompatibility properties. They can be used either in combination with other biomacromolecules or particles or even exclusively for the enhancement of bone regeneration or for the development of biomimetic scaffolds. Collagen or gelatin derivatives can be transformed into nanofibrous materials with porous micro- or nanostructures and superior mechanical properties and biocompatibility using electrospinning technology. Specific attention was recently paid to electrospun mats of such biopolymers, due to their high ratio of surface area to volume, as well as their biocompatibility, biodegradability, and low immunogenicity. The fiber mats with submicro- and nanometer scale can replicate the extracellular matrix structure of human tissues and organs, making them highly suitable for use in tissue engineering due to their exceptional bioaffinity. The drawbacks may include rapid degradation and complete dissolution in aqueous media. The use of gelatin/collagen electrospun nanofibers in this form is thus greatly restricted for biomedicine. Therefore, the cross-linking of these fibers is necessary for controlling their aqueous solubility. This led to enhanced biological characteristics of the fibers, rendering them excellent options for various biomedical uses. The objective of this review is to highlight the key research related to the electrospinning of collagen and gelatin, as well as their applications in the biomedical field. The review features a detailed examination of the electrospinning fiber mats, showcasing their varying structures and performances resulting from diverse solvents, electrospinning processes, and cross-linking methods. Judiciously selected examples from literature will be presented to demonstrate major advantages of such biofibers. The current developments and difficulties in this area of research are also being addressed.

Influence of Placement of Lumbar Interbody Cage on Subsidence Risk: Biomechanical Study.

OBJECTIVE: Lumbar spinal fusion is a common surgical procedure that can be done with a variety of different instrumentation and techniques. Despite numerous research studies investigating subsidence risk factors, the impact of cage placement on subsidence is not fully elucidated. This study aims to determine whether placement of an expandable transforaminal lumbar interbody fusion cage at the center end plate or at the anterior apophyseal ring affects cage subsidence. METHODS: A transforaminal lumbar interbody fusion cage was placed centrally or peripherally between 2 synthetic vertebral models of L3 and L4. A compression plate attached to a 10 KN load cell was used to uniaxially compress the assembly. The ultimate force required for the assembly to fail and subsidence stiffness were analyzed. Computed tomography scans of each L3 and L4 were obtained, and maximum end plate subsidence was measured in the frontal plane. RESULTS: Anterior apophyseal cage placement resulted in higher stiffness of the vertebrae-cage assembly (Ks, 962.89 N/mm) and a higher subsidence stiffness (Kb,987.21 N/mm) compared with central placement (P < 0.05). Ultimate compressive load of the vertebrae-cage assembly did not increase. Moreover, the maximum subsidence depth did not significantly vary between placements. CONCLUSIONS: The subsidence stiffness increased with anterior apophyseal cage placement. Periphery end plate cortical bone architecture may play a role in resisting the impact of cage subsidence. To fully understand the effect of cage placement on cage subsidence, future studies should investigate its implications on native and diseased spine.

Diblock and Triblock Copolymers as Nanostructured Precursors to Functional Nanoporous Materials: From Design to Application.

Block copolymers have gained tremendous interest from the scientific community in the last two decades. These macromolecular architectures indeed constitute ideal nanostructured precursors for the generation of nanoporous materials meant for various high added value applications. The parallel emergence of controlled polymerization techniques has notably enabled to finely control their molecular features to confer them with unique structural and physicochemical properties, such as low dispersity values (D), well-defined volume fractions, and controlled functionality. The nanostructuration and ordering of diblock or triblock copolymers, which can be achieved through various experimental techniques, including channel die processing, solvent vapor or thermal annealing, nonsolvent-induced phase separation or concomitant self-assembly, and nonsolvent-induced phase separation, allows for the preparation of orientated microphase-separated copolymers whose morphology is dictated by three main factors, i.e., Flory-Huggins interaction parameter between constitutive blocks, volume fraction of the blocks, and polymerization degree. This review article provides an overview of the actual state of the art regarding the preparation of functional nanoporous materials from either diblock or triblock copolymers. It will also highlight the major applications of such peculiar materials.

An Ex Vivo Model of Posterior Tracheomalacia With Evaluation of Potential Treatment Modalities.

OBJECTIVE: Posterior tracheomalacia (TM) is characterized by excessive intraluminal displacement of the tracheal membranous wall. Recently, novel surgical strategies for repair of posterior TM have been introduced. To our knowledge, these strategies have not been evaluated in a model of posterior TM. Thus, we sought to design an ex vivo mechanical model of posterior TM to evaluate potential repair interventions. METHODS: A model for posterior TM was created with partial thickness longitudinal incisions to the posterior aspect of ex vivo porcine trachea. Three groups of tracheas were tested: (1) control (unmanipulated), (2) posterior TM (injury), and (3) intervention (repair). Interventions included external splinting with 0.3 and 0.5 mm bioresorbable plates, posterior tracheopexy, and injection tracheoplasty with calcium hydroxylapatite. An airtight tracheal system was created to measure tracheal wall collapse with changes in negative pressure. A bronchoscope and pressure transducer were connected to either end. Cross-sectional area of the tracheal lumen was analyzed using ImageJ software (National Institutes of Health, Bethesda, MD). RESULTS: Average percent reduction in cross-sectional area of the tracheal lumen was compared using a two-tailed paired t-test. Significant differences were found between control and TM groups (p < 0.019). There was no significant difference between control and external splinting and posterior tracheopexy groups (p > 0.14). CONCLUSION: We describe an ex vivo model for posterior TM that replicates airway collapse. External splinting and tracheopexy interventions showed recovery of the injured tracheal segment. Injection tracheoplasty did not improve the TM. LEVEL OF EVIDENCE: N/A Laryngoscope, 133:2000-2006, 2023.

Tendon Transection Healing Can Be Improved With Adipose-Derived Stem Cells Cultured With Growth Differentiation Factor 5 and Platelet-Derived Growth Factor.

BACKGROUND: As hand surgeons, tendon injuries and lacerations are a particularly difficult problem to treat, as poor healing potential and adhesions hamper optimal recovery. Adipose-derived stem cells (ADSCs) have been shown to aid in rat Achilles tendon healing after a puncture defect, and this model can be used to study tendon healing in the upper extremity. We hypothesized that ADSCs cultured with growth differentiation factor 5 (GDF5) and platelet-derived growth factor (PDGF) would improve tendon healing after a transection injury. METHODS: Rat Achilles tendons were transected and then left either unrepaired or repaired. Both groups were treated with a hydrogel alone, a hydrogel with ADSCs, or a hydrogel with ADSCs that were cultured with GDF5 and PDGF prior to implantation. Tissue harvested from the tendons was evaluated for gene expression of several genes known to play an important role in successful tendon healing. Histological examination of the tendon healing was also performed. RESULTS: In both repaired and unrepaired tendons, those treated with ADSCs cultured with GDF5/PDGF prior to implantation showed the best tendon fiber organization, the smallest gaps, and the most organized blood vessels. Treatment with GDF5/PDGF increased expression of the protenogenesis gene SOX9, promoted cell-to-cell connections, improved cellular proliferation, and enhanced tissue remodeling. CONCLUSIONS: Adipose-derived stem cells cultured with GDF5/PDGF prior to implantation can promote tendon repair by improving cellular proliferation, tenogenesis, and vascular infiltration. This effect results in a greater degree of organized tendon healing.

Effects of Premixing Betamethasone and Lidocaine on Chondrocyte Inflammation in an In Vitro Model.

BACKGROUND: It is common practice for hand surgeons to premix corticosteroids with a local anesthetic and store the mixture in pre-loaded syringes for rapid use during clinic. However, any possible loss of efficacy with this practice has never been studied. The purpose of this study, therefore, is to determine whether premixing betamethasone sodium phosphate/betamethasone acetate (BSP) and lidocaine (L) at different time intervals from injection has diminishing anti-inflammatory effects on chondrocytes in vitro. METHODS: Human articular chondrocytes were partitioned into six groups: two controls and four experimental conditions. The negative control had growth media only. The positive control had growth media and inflammatory cytokines (interleukin-1ß and oncostatin M). Experimental conditions were additionally treated with BSP alone or BSP mixed with lidocaine (BSP + L) at the time of treatment (0 hours), or at 4 or 24 hours prior. Relative expressions of inflammatory genes were measured. RESULTS: Relative to the positive control, chondrocytes in all experimental conditions decreased expression of TNF-α, MMP-3, and ADAMTS-4. Chondrocytes exposed to BSP only or BSP + L at 4 hours or 24 hours prior to treatment decreased expression of IL-8. Chondrocytes exposed to BSP only or BSP + L at 0 hours or 4 hours prior to treatment decreased expression of MMP-1. There were no significant differences in expression of IL-6 or MMP-13. CONCLUSIONS: Treatment with BSP + L prepared in pre-loaded syringes at varying time intervals up to 24 hours prior to injection does not significantly impact the ability of the mixture to reduce expression of certain key inflammatory mediators in vitro.

Synthesis of Thioureas, Thioamides, and Aza-Heterocycles via Dimethyl-Sulfoxide-Promoted Oxidative Condensation of Sulfur, Malonic Acids, and Amines.

Malonic acid and derivatives have been well-known to undergo monodecarboxylation under relatively mild conditions and have been exclusively used as a C2 synthon. We report herein their new application as a C1 synthon via double decarboxylation promoted by sulfur and dimethyl sulfoxide. In the presence of amines as nucleophiles, a wide range of thioureas and thioamides as well as N-heterocycles were obtained in good to excellent yields under mild heating conditions.

Effect of Amino-Functionalized Polyhedral Oligomeric Silsesquioxanes on Structure-Property Relationships of Thermostable Hybrid Cyanate Ester Resin Based Nanocomposites.

Nanocomposites of cyanate ester resin (CER) filled with three different reactive amino-functionalized polyhedral oligomeric silsesquioxane (POSS) were synthesized and characterized. The addition of a small quantity (0.1 wt.%) of amino-POSS chemically grafted to the CER network led to the increasing thermal stability of the CER matrix by 12-15 °C, depending on the type of amino-POSS. A significant increase of the glass transition temperature, Tg (DSC data), and the temperature of α relaxation, Tα (DMTA data), by 45-55 °C of the CER matrix with loading of nanofillers was evidenced. CER/POSS films exhibited a higher storage modulus than that of neat CER in the temperature range investigated. It was evidenced that CER/aminopropylisobutyl (APIB)-POSS, CER/N-phenylaminopropyl (NPAP)-POSS, and CER/aminoethyl aminopropylisobutyl (AEAPIB)-POSS nanocomposites induced a more homogenous α relaxation phenomenon with higher Tα values and an enhanced nanocomposite elastic behavior. The value of the storage modulus, E', at 25 °C increased from 2.72 GPa for the pure CER matrix to 2.99-3.24 GPa for the nanocomposites with amino-functionalized POSS nanoparticles. Furthermore, CER/amino-POSS nanocomposites possessed a higher specific surface area, gas permeability (CO2, He), and diffusion coefficients (CO2) values than those for neat CER, due to an increasing free volume of the nanocomposites studied that is very important for their gas transport properties. Permeability grew by about 2 (He) and 3.5-4 times (CO2), respectively, and the diffusion coefficient of CO2 increased approximately twice for CER/amino-POSS nanocomposites in comparison with the neat CER network. The efficiency of amino-functionalized POSS in improving the thermal and transport properties of the CER/amino-POSS nanocomposites increased in a raw of reactive POSS containing one primary (APIB-POSS) < eight secondary (NPAP-POSS) < one secondary and one primary (AEAPIB-POSS) amino groups. APIB-POSS had the least strongly pronounced effect, since it could form covalent bonds with the CER network only by a reaction of one -NH2 group, while AEAPIB-POSS displayed the most highly marked effect, since it could easily be incorporated into the CER network via a reaction of -NH2 and -NH- groups with -O-C≡N groups from CER.