The effect of papaverine on tendon healing and adhesion in rats following Achilles tendon repair.

OBJECTIVES: The study aimed to examine the histopathological and biomechanical effects of papaverine administered intraperitoneally and locally on Achilles tendon healing in a rat model. MATERIALS AND METHODS: Forty-eight adult male Sprague-Dawley rats (range, 300 to 400 g) were used in this study conducted between October and November 2022. The rats were divided into three groups, with each group further subdivided into two for sacrifice on either the 15th (early period) or 30th (late period) day after surgery. The first (control) group received no treatment following Achilles tendon repair, while papaverine was intraperitoneally administered every other day for 10 days in the second group and locally in the third group after surgery. On the 15th and 30th days, the rats were sacrificed, and their Achilles tendons were subjected to biomechanical testing and histopathological evaluation. RESULTS: Histopathologically, there were no significant differences among the groups on the 15th day. However, on the 30th day, the locally applied papaverine group exhibited superior histopathological outcomes compared to the control group (p<0.05). Concerning the highest tensile strength values before rupture, the biomechanical assessment showed that the group receiving local papaverine treatment in the early period and both the group with systemic papaverine treatment and the one with local papaverine treatment in the late period displayed a statistically significant advantage compared to the control group (p<0.05). CONCLUSION: Locally administered papaverine has positive biomechanical effects in the early period and exhibits a positive correlation both histopathologically and biomechanically in the late period. Novel therapeutic options may be provided for patients through these findings.

Alginate with citrus pectin and pterostilbene as healthy food packaging with antioxidant property.

A new type of film packaging made from natural polysaccharide materials, with its environmental safety and friendliness, is considered as a potential substitute for plastics. Novel polysaccharide composite films based upon citrus pectin (CP) and sodium alginate (SA) were successfully prepared and characterized, containing pterostilbene (PTE) at various concentrations (0.2, 0.4, 0.8, 1.6, 3.2 mM). The rheological analysis displayed that all film-forming liquids performed no gelation behavior with G" > G' at low frequency and weak gelation with G" < G' at high frequency. The SA-CP films had good tensile strength (TS) and elongation at break (EB), while adding PTE as an antioxidant to the film reduced both the values. Of note, the SA-CP films with PTE had better moisture resistance than that of the pure SA-CP films, which was related to the changes of its microstructure. The increased roughness of the films containing PTE was observed by microscope. After calcium chloride cross-linking, the water solubility of the films was reduced, while its thermal stability was improved. Notably, the accretion of PTE expressively enhanced the antioxidant properties of the SA-CP films. Thus, the SA-CP composite films containing PTE could be utilized as an excellent antioxidant packaging material.

Thermoplastic mung bean starch/natural rubber/sericin blends for improved oil resistance.

Oil resistant thermoplastic elastomers (TPE) were prepared using mung bean thermoplastic starch (MTPS) blending with rubbers and sericin. Sericin was incorporated into MTPS as a compatibilizer. MTPS with sericin (MTPSS) was blended with natural rubber (NR) and epoxidized NR (ENR). Sericin at 5% improved the tensile strength (10 MPa), elastic recovery (52%) and morphology of the MTPSS/ENR blend. The mechanical properties, elastic recovery and morphology of the MTPSS5/NR blend were improved by the addition of ENR. The MTPSS/ENR showed palm (28%) and motor oils (8%) swelling resistance because of the hydrophilicity of MTPS and high polarity of ENR. The MTPSS/ENR/NR showed gasoline swelling resistance (104%) because of the hydrophilicity of MTPS and low polarity of NR. FTIR confirmed a reaction between the -NH groups of sericin and the epoxy groups of ENR. This reaction improved the compatibility, mechanical properties, elastic recovery, morphology and oils swelling resistance of the blends.

Impact on Mechanical Properties of 10 versus 20 Minute Treatment of Human Pericardium with Glutaraldehyde in OZAKI Procedure.

PURPOSE: The aim of this study was to analyze the effects of 10-minute (standard term) versus 20-minute treatment with glutaraldehyde (GA) on mechanical stability and physical strength of human pericardium in the setting of the OZAKI procedure. METHODS: Leftover pericardium (6 patients) was bisected directly after the operation, and one-half was further fixed for 10 additional minutes. Uniaxial tensile tests were performed and ultimate tensile strength (UTS), ultimate tensile strain (uts), and collagen elastic modulus were evaluated. RESULTS: Both treatments resulted in similar values of uniaxial stretching-generated elongations at rupture (10 minutes 25 ± 7 % vs. 20 minutes: 22 ± 5 %; p = 0.05), UTS (5.16 ± 2 MPa vs. 6.54 ± 3 MPa; p = 0.59), and collagen fiber stiffness (elastic modulus: 31.80 ± 15.05 MPa vs. 37.35 ± 15.78 MPa; p = 0.25). CONCLUSION: Prolongation of the fixation time of autologous pericardium has no significant effect on its mechanical stability; thus, extending the intraoperative treatment cannot be recommended.

Bioinspired tissue-compliant hydrogels with multifunctions for synergistic surgery-photothermal therapy.

Operation therapy is a common treatment for many cancers, but malignant tumors likely recur and metastasize after surgery, resulting in treatment failure. In this study, we aimed at synthesizing a multifunctional hydrogel patch that features multifunctions for synergistic surgery-photothermal therapy. Our polydopamine nanoparticle (PDA NP)-crosslinked poly(acrylamide-co-N-(3-aminopropyl)methacrylamide) hydrogels undergo several dynamic interactions (e.g., hydrogen bonds, π-π interactions, and imine bonds), which confer high stretchability (∼3430%) and adhesive strength to porcine skin (∼75 kPa) that mimics soft wound tissues. Furthermore, PDA NP incorporation into the hydrogel matrix endows it with photothermal responsivity under 808 nm irradiation. As a proof of concept, our hydrogel system was used to ablate residual tumors in 4T1 tumor-bearing mice models after surgery via photothermal therapy. We find that synergistic operation-photothermal therapy effectively eradicates solid tumors and prevents cancer recurrence in mice. We envision that our work provides an effective synergistic strategy for cancer treatment and offers great potential for clinical applications.

A combined-modification method of carboxymethyl ß-cyclodextrin and lignin for nano-hydroxyapatite to reinforce poly(lactide-co-glycolide) for bone materials.

Lignin is the second most abundant natural biomacromolecule. A new surface-modification for nano-hydroxyapatite (n-HA) by carboxymethyl ß-cyclodextrin (CM-ß-CD) and lignin and its reinforce effect for poly(lactide-co-glycolide) (PLGA) were investigated by Fourier transformation infrared (FTIR), X-ray diffraction pattern (XRD), transmission electron microscopy (TEM), thermal gravimetric analysis (TGA), dispersion images, the tensile tests, scanning electron microscope (SEM), differential scanning calorimeter (DSC) and polarized optical microscopy (POM), compared to the singled-modification of CM-ß-CD or lignin. The results showed that the appropriate combined-modified n-HA displayed excellent synergistic effects for increasing the dispersion, yielding good interfacial bonding between n-HA with PLGA matrix. The tensile strength of the composite was still 14.53% higher than that of PLGA, for a n-HA addition amount of 15 wt%, which was significantly better than that for the singled-modified n-HA. Additionally, in vitro degradation behavior was evaluated by soaking in simulated body fluid (SBF), and their cell response was carried out by interaction tests with bone mesenchymal stem cells. The results indicated that the combined-modification method promoted good degradation behavior and apatite deposition, as well as excellent cell biocompatibility. This study may offer an important guidance to obtain PLGA-based composites reinforced by surface-modified n-HA as bone materials.

Improved tendon healing by a combination of Tanshinone IIA and miR-29b inhibitor treatment through preventing tendon adhesion and enhancing tendon strength.

Background: Despite significant advances in the materials and methods development used in surgical repair and postoperative rehabilitation, the adhesion formation remains the most common clinical problem in tendon injuries. Therefore, the development of novel therapies is necessary for targeting at preventing tendon adhesion formation and improving tendon strength. Methods: We used rat fibroblasts for in vitro experiments to determine the optimal concentration of TSA in rats, and then set up negative control group, TSA intervention group, mir-29b interference adenovirus intervention group and TSA and mir-29b interference adenovirus co-intervention group. By comparing cell proliferation and protein expression in different group, we verified the effect and mechanism of drugs on fibroblast function. At the same time, the Sprague-Dawley rat Achilles tendon model in vivo was established in this study, which was divided into sham operation group and operation group. Afterwards in the operation group, mir-29b inhibitor and placebo were injected every 3 days respectively. Then the injection inhibitor group was divided into 5 groups which mean TSA was injected into the marked area at 0, 6, 24 and 72 hours after operation for 1 week, finally all of the rats were died at 3 weeks after operation. Through the observation of general properties, histological observation of Achilles tendon injury, biomechanical test and cell and protein expression in rats' tendon cell, the effect of drugs on tendon adhesion formation was analyzed. Results: We demonstrated that the combination of miR-29b inhibitor and tanshinone IIA(TSA) could prevent tendon adhesion and also enhance tendon strength. Mechanically, the miR-29b inhibitor could activate the TGF-ß/Smad3 pathway to trigger endogenous pathways and induce a high proliferation of fibroblast. Subsequently, we also found adding TSA after 6 hours of miR-29b treatment gave less cell cytotoxicity in our rat model with better outcome of less tendon adhesion and enhanced strength. Conclusion: We conclude that the use of miR-29b inhibitor at the end of the tendon break could initiate endogenous repair mechanism and subsequently use of TSA should be able to inhibit the exogenous repair mechanism. Therefore, the combination of both treatments could prevent tendon adhesion and ensure tendon strength. Our findings suggested that this approach would be a feasible approach for tendon repair.

Stimulatory Effects of Boron Containing Bioactive Glass on Osteogenesis and Angiogenesis of Polycaprolactone: In Vitro Study.

Polycaprolactone (PCL) has attracted great attention for bone regeneration attributed to its cost-efficiency, high toughness, and good processability. However, the relatively low elastic modulus, hydrophobic nature, and insufficient bioactivity of pure PCL limited its wider application for bone regeneration. In the present study, the effects of the addition of boron containing bioactive glass (B-BG) materials on the mechanical properties and biological performance of PCL polymer were investigated with different B-BG contents (0, 10, 20, 30, and 40 wt.%), in order to evaluate the potential applications of B-BG/PCL composites for bone regeneration. The results showed that the B-BG/PCL composites possess better tensile strength, human neutral pH value, and fast degradation as compared to pure PCL polymers. Moreover, the incorporation of B-BG could enhance proliferation, osteogenic differentiation, and angiogenic factor expression for rat bone marrow stromal cells (rBMSCs) as compared to pure PCL polymers. Importantly, the B-BG also promoted the angiogenic differentiation for human umbilical vein endothelial cells (HUVECs). These enhanced effects had a concentration dependence of B-BG content, while 30 wt.% B-BG/PCL composites achieved the greatest stimulatory effect. Therefore the 30 wt.% B-BG/PCL composites have potential applications in bone reconstruction fields.

Evaluating the bioactivity of a hydroxyapatite-incorporated polyetheretherketone biocomposite.

BACKGROUND: Polyetheretherketone (PEEK) exhibits stable chemical properties, excellent biocompatibility, and rational mechanical properties that are similar to those of human cortical bone, but the lack of bioactivity impedes its clinical application. METHODS: In this study, hydroxyapatite (HA) was incorporated into PEEK to fabricate HA/PEEK biocomposite using a compounding and injection-molding technique. The tensile properties of the prepared HA/PEEK composites (HA content from 0 to 40 wt%) were tested to choose an optimal HA content. To evaluate the bioactivity of the composite, the cell attachment, proliferation, spreading and alkaline phosphatase (ALP) activity of MC3T3-E1 cells, and apatite formation after immersion in simulated body fluid (SBF), and osseointegration in a rabbit cranial defect model were investigated. The results were compared to those from ultra-high molecular weight polyethylene (UHMWPE) and pure PEEK. RESULTS: By evaluating the tensile properties and elastic moduli of PEEK composite samples/PEEK composites with different HA contents, the 30 wt% HA/PEEK composite was chosen for use in the subsequent tests. The results of the cell tests demonstrated that PEEK composite samples/PEEK composite exhibited better cell attachment, proliferation, spreading, and higher ALP activity than those of UHMWPE and pure PEEK. Apatite islands formed on the HA/PEEK composite after immersion in SBF for 7 days and grew continuously with longer time periods. Animal tests indicated that bone contact and new bone formation around the HA/PEEK composite were more obvious than those around UHMWPE and pure PEEK. CONCLUSIONS: The HA/PEEK biocomposite created by a compounding and injection-molding technique exhibited enhanced osteogenesis and could be used as a candidate of orthopedic implants.

Production and characterization of CMC-based antioxidant and antimicrobial films enriched with chickpea hull polysaccharides.

In the present study, polysaccharides from chickpea hull (CHPS) were incorporated into carboxymethyl cellulose (CMC) for the development of CMC-based films. The physical and mechanical properties, color, transmittance, antioxidant and antimicrobial activities were investigated, and differential scanning calorimetry (DSC), Fourier transform-infrared (FT-IR) spectroscopy and thermogravimetric analysis (TGA) were applied to study the potential interaction, structure and thermal stabilization of the prepared films. The results revealed that some physical and mechanical properties of films, like moisture content, elongation at break and water vapor permeability, were decreased. While thickness, swelling ratio, water solubility and tensile strength were significantly increased (p < 0.05) compared with control film. Furthermore, the films exhibited potential antioxidant effects on DPPH and ABTS free radicals. The results of scanning electron microscopy showed rough and heterogeneous morphology for CMC-CHPS films while control film exhibited smooth, homogenous and compact structure. FT-IR results reflected good interaction of chemical groups and bonds between CMC and CHPS. DSC results showed that glass transition temperature increased significantly (p < 0.05) from 82.68 to 90.39 °C compared with control of 78.21 °C. Thermal stability of all films was improved, indicating that the films could be used as biocomposite materials for packaging of food products.

Electrospun Heparin-Loaded Core-Shell Nanofiber Sutures for Achilles Tendon Regeneration In Vivo.

Achilles tendon reconstruction surgery is the primary clinical method for repairing acute Achilles tendon ruptures. However, the efficacy of the postoperative healing process and the recovery of physiological function are inadequate. This study examines the healing mechanism of ruptured rat Achilles tendons seamed with heparin-loaded core-shell fiber sutures fabricated via near-field electrospinning. High-heparin-concentration sutures (PPH3.0) perform better than the low-heparin-concentration sutures and commercial sutures (CSs). The PPH3.0 suture recruits fewer inflammatory cells and shows good histocompatibility in peritoneal implantation experiments. Staining of the Achilles tendon rupture repair zone demonstrates that a high heparin concentration in sutures reduces immune-inflammatory responses. Immunohistochemical analysis reveals that the transforming growth factor-ß staining scores of the PPH3.0 sutures are not significantly different from those of the corresponding control group but are significantly different from those of the CSs and non-heparin-loaded-suture groups. According to vascular endothelial growth factor (VEGF) analysis, the concentration of VEGF in the group treated with the PPH3.0 suture increases by 37.5% compared with that in its control group. No significant difference in tension strength is observed between the PPH3.0 group and healthy Achilles tendons. These findings illustrate that this novel method effectively treats Achilles tendon rupture and promotes healing and regeneration.

Lafoensia pacari A. St.-Hil.: Wound healing activity and mechanism of action of standardized hydroethanolic leaves extract.

ETHNOPHARMACOLOGICAL IMPORTANCE: Lafoensia pacari A. St.-Hil., (Lythraceae) is a native tree of Brazilian Cerrado and commonly known in Brazil as "mangava-brava". Its leaves are used in Brazilian folk medicine in wound healing, cutaneous mycoses, and in the treatment of gastritis and ulcers. AIM OF THE STUDY: The present study was designed to evaluate the wound healing activity and mechanism of action of the hydroethanolic extract of Lafoensia pacari A. St.-Hil. leaves (HELp), and to advance in its chemical profiling. MATERIALS AND METHODS: HELp was prepared by maceration in 70% hydroethanolic solution (1:10, w/v). The phytochemical analyses were investigated using colorimetry and electrospray ionization/mass spectrometric detection (ESI-MSn). Its in vitro cytotoxicity was evaluated in CHO-K1 and L929 cells, while the in vivo acute toxicity was performed in mice. The potential in vivo wound healing activity was assessed using excision and incision rat models and histopathology of the wounded skin (excision model) was carried out. The in vitro wound healing activity of HELp was demonstrated by scratch assay in L-929 cells, by measuring proliferation/migration rate and p-ERK 1/2 protein expression using western blot analysis. HELp's in vivo anti-inflammatory activity was evaluated by lipopolysaccharide (LPS) induced peritonitis in mice, along with the determination of nitric oxide (NO) and cytokines (TNF-α and IL-10) in the peritoneal lavages. Its potential in vitro antibacterial activity was performed using microbroth dilution assay, while in vitro antioxidant activities was by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, and ferric reducing antioxidant power (FRAP) assays. RESULTS: The phytochemical analysis of HELp revealed the presence of polyphenols with ellagic acid, punicalagin, punicalin, kaempferol, quercetin-3-O-xylopyranoside and quercetin-3-O-rhamnopyranoside being the most prominent. HELp showed no toxicity on CHO-k1 and L929 cell lines. Topical treatment with HELp (10 and 30 mg/g of gel) presented increased rates of wound contraction at all the days evaluated with complete wound re-epithelialization at 22.0 ±â€¯1.5 (p < 0.05) and 21.7 ±â€¯1.6 (p < 0.01) days, respectively. Topical application of HELp (10, 30 or 100 mg/g of gel) in incised wounds caused an increase in tensile break strength at all concentrations resulting in moderate re-epithelialization and neovascularization, increased cell proliferation an accelerated remodeling phase of the wound, in a manner comparable to standard drug (Madecassol®, 10 mg/g). In the scratch assay with L929 cells, HELp (0.1 and 0.03 mg/mL) and PDGF (5 ng/mL) resulted in the increased proliferation/migration rate of fibroblasts and higher expression of p-ERK 1/2 protein. In LPS-induced peritonitis, HELp (100 and 200 mg/kg p.o.) decreased total leukocyte migration, comparable to the dexamethasone (0.5 mg/kg p.o.). In RAW 264.7 macrophages activated by LPS, HELp produced anti-inflammatory activity dependent on increased concentrations of IL-10, reduction in NO production, without altering the TNF-α levels. HELp also presented potent antioxidant activity in the DPPH and FRAP, but lacks in vitro antibacterial activity. CONCLUSION: The present study results support the popular use of the leaves of L. pacari in the treatment of wounds. Its wound healing activity is multi-targeted and involves inhibition of the proliferative and anti-inflammatory phases, antioxidant and positive modulation of the remodeling phase that might be involved different secondary metabolites, with emphasis on the ellagic acid, punicalagin, punicalin, kaempferol, quercetin-3-O-xylopyranoside and quercetin-3-O-rhamnopyranoside.

Novel alginate/hydroxyethyl cellulose/hydroxyapatite composite scaffold for bone regeneration: In vitro cell viability and proliferation of human mesenchymal stem cells.

Sodium alginate (SA)/hydroxyethylcellulose (HEC)/hydroxyapatite (HA) composite scaffolds were explored for enhanced in vitro bone regeneration. The SA/HEC/HA composites were synthesized using the lyophilization technique and further cross-linked in the presence of calcium ions to form composite hydrogel networks. The physicochemical, thermal behavior and morphology properties of the prepared scaffolds were characterized through XRD, DSC/TGA, FTIR and SEM. Furthermore, the mechanical behavior of the under investigated scaffolds was determined using texture analyzer. The in vitro bioactivity in SBF and adsorption of bovine serum albumin as well as cell viability for all the prepared scaffolds were also tested. The results indicated that the higher HA concentration (40wt%) enhanced the mechanical properties (23.9MPa), bioactivity and protein adsorption. Cell viability of the tested scaffolds confirmed the non-toxicity of the fabricated systems on the human mesenchymal stem cells (hMSCs). Proliferation capability was also confirmed for the tested scaffolds after 3 and 7days, but the higher HA-containing scaffold showed increased cell populations specially after 7days compared to HA-free scaffolds. This novel composite material could be used in bone tissue engineering as a scaffold material to deliver cells and biologically active molecules.

Prevention of Peritendinous Adhesion Formation After the Flexor Tendon Surgery in Rabbits: A Comparative Study Between Use of Local Interferon-α, Interferon-ß, and 5-Fluorouracil.

BACKGROUND: Peritendinous adhesion is the most common complication after tendon surgery, particularly in zone II of the hand. Prevention of inflammation around the tendon, which develops after trauma and surgery, can decrease the tendon adhesion formation. This study compares the effect of some anti-inflammatory cytokines with 5-fluorouracil (5-FU) on the tensile strength and in prevention of peritendinous adhesion formation. METHODS: Sixteen rabbits were allocated equally into 4 groups. Tendons of the index and ring fingers in zone II of the right hind paw were cut in all animals and then repaired. Interferon (IFN)-α in group 1, 5-FU in group 2, normal saline in group 3, and IFN-ß in group 4 were locally applied to the repaired sites. Three weeks later, tensometric and histopathologic evaluations were performed. RESULTS: The force required for removing the tendon from the sheath was not different between the groups (P = 0.130), but the time required for removal was significantly shorter in 5-FU group (P = 0.049). The strength of repair was not different between the groups in terms of force and time needed for rupture (P = 0.11 and 0.67, respectively). In histopathologic examination, normal architecture of the tendon and peritendon environment was less disturbed in the IFN groups, especially in IFN-ß specimens. CONCLUSIONS: Local application of 5-FU significantly reduced peritendinous adhesion. Local IFN-α and IFN-ß had no significant effect on the prevention of peritendinous adhesion formation. The strength of the repair was not affected by these cytokines and 5-FU.

Ropivacaine alters the mechanical properties of hamstring tendons: In vitro controlled mechanical testing of tendons from living donors.

OBJECTIVE: Intraarticular or periarticular injection of ropivacaine (RI) is an element of current knee surgery practices. The goal of this study was to determine the effects of RI on the mechanical properties of hamstring tendons. We hypothesized that RI would have a detrimental effect on the mechanical properties of periarticular soft tissues METHODS: A tensile test to failure was performed on 120 hamstring tendon segments harvested during ACL reconstruction surgery in 120 patients. Two sets of tensile tests were done. The first evaluated the effect of RI itself on the mechanical properties of tendons: 30 samples were soaked for 1hour in a 2% RI solution and compared to 30 samples soaked in a saline solution (control group). The second evaluated the effect of RI concentration on the mechanical properties of hamstring tendons: 30 samples were soaked for 1hour in a 2% RI solution and 30 samples were soaked in a 7.5% RI solution. RESULTS: In the first test, 29 samples from each group were analyzed as two samples (one in each group) failed at the grip interface. The specimens exposed to 2% RI had lower ultimate tensile strength (Δ=4.4MPa, P=0.001), strain energy (Δ=13MPa, P=0.001) and Young's modulus (Δ=1.6MPa, P=0.02) than the specimens in the control group. There was no significant difference in the strain at failure between groups (Δ=5%, P=0.3). In the second test, one specimen from the 7.5% RI group failed during the preloading and was excluded. There was no significant difference in terms of the load at failure and ultimate tensile stress (Δ=0.45MPa, P=0.6) and strain energy (Δ=0.49MPa, P=0.49) between the two groups. There were significant differences in terms of elongation at failure (Δ=28%, P=0.0003) and Young's modulus (Δ=2.6MPa, P=0.005), with the specimens exposed to 7.5% RI undergoing greater deformation and having a lower Young's modulus. DISCUSSION: While local RI injections are widely performed in clinical practice, the results of this in vitro study point to short-term alterations of the mechanical properties of hamstring tendons. If these results hold in vivo, this could lead to weakness of the soft tissues exposed to this product, particularly the tendons and ligaments around the injection area. LEVEL OF EVIDENCE: Experimental study. Level 1.

Cellular scale model of growth plate: An in silico model of chondrocyte hypertrophy.

The growth plate is the responsible for longitudinal bone growth. It is a cartilaginous structure formed by chondrocytes that are continuously undergoing a differentiation process that starts with a highly proliferative state, followed by cellular hypertrophy, and finally tissue ossification. Within the growth plate chondrocytes display a characteristic columnar organization that potentiates longitudinal growth. Both chondrocyte organization and hypertrophy are highly regulated processes influenced by biochemical and mechanical stimuli. These processes have been studied mainly using in vivo models, although there are few computational approaches focused on the rate of ossification rather than events at cellular level. Here, we developed a model of cellular behavior integrating biochemical and structural factors in a single column of cells in the growth plate. In our model proliferation and hypertrophy were controlled by biochemical regulatory loop formed between Ihh and PTHrP (modeled as a set of reaction-diffusion equations), while cell growth was controlled by mechanical loading. We also examined the effects of static loading. The model reproduced the proliferation and hypertrophy of chondrocytes in organized columns. This model constitutes a first step towards the development of mechanobiological models that can be used to study biochemical interactions during endochondral ossification.

The Role of Epithelial to Mesenchymal Transition in Human Amniotic Membrane Rupture.

Context: Biochemical weakening of the amnion is a major factor preceding preterm premature rupture of membranes (PPROMs), leading to preterm birth. Activation of matrix metalloproteinases (MMPs) is known to play a key role in collagen degradation of the amnion; however, epithelial to mesenchymal transition (EMT) that is also induced by MMP activation has not been investigated as a mechanism for amnion weakening. Objective: To measure amniotic EMT associated with vaginal delivery (VD) compared with unlabored cesarean sections (CSs), and to assess changes in amniotic mechanical strength with pharmacologic inhibitors and inducers of EMT, thus testing the hypothesis that EMT is a key biochemical event that promotes amniotic rupture. Findings: (1) Amnions taken from VD contained a significantly increased number of mesenchymal cells relative to epithelial cells compared with unlabored CS by fluorescence-activated cell sorting analysis (60% vs 10%); (2) tumor necrosis factor (TNF)-α stimulation of amniotic epithelial cells increased expression of the mesenchymal marker vimentin after 2 days; (3) EMT inhibitor, etodolac, significantly increased the time and mechanical pressure required to rupture the amnion; and (4) TNF-α and another pharmacologic EMT inducer, ethacridine, decreased the time and mechanical pressure required for amnion rupture, further confirming that the mesenchymal phenotype significantly weakens the amnion. Conclusions: This work demonstrated amniotic cell EMT was associated with labor and EMT decreased the tensile strength of the amnion. These findings suggest a role for EMT in the pathophysiology of PPROM and may provide a basis for development of therapies to prevent preterm labor.

Layer-by-Layer Thin Films for Co-Delivery of TGF-ß siRNA and Epidermal Growth Factor to Improve Excisional Wound Healing.

The major challenge with treatment of dermal wounds is accelerating healing process, while preventing the scar formation. Herein, we have fabricated layer-by-layer (LbL) polyelectrolyte multilayer films containing epidermal growth factor (EGF) and TGF-ß siRNA to improve excisional wound healing and decrease scar formation. The chitosan and sodium alginate LbL thin films showed 13.0 MPa tensile strength and 2.22 N/cm2 skin adhesion strength. The LbL thin films were found to be cytocompatible, where A431 epidermal keratinocytes adhered to the film and showed 86.2 ± 0.8% cell growth compared with cells cultured in the absence of LbL thin film. In contrast, LbL thin film did not promote the Escherichia coli and Staphylococcus aureus bacterial colony formation. In a C57BL/6 mouse excisional wound model, application of LbL thin films containing TGF-ß siRNA significantly (p < 0.05) reduced the TGF-ß protein expression and collagen production. The LbL thin films containing EGF showed improved wound contraction (<9 days post excision). The co-delivery of TGF-ß siRNA and EGF using LbL thin films resulted in accelerated wound healing and decreased collagen deposition. Furthermore, the LbL thin films with TGF-ß siRNA and EGF combination showed greater reepithelialization. Taken together, we have successfully demonstrated the co-delivery of TGF-ß siRNA and EGF peptide using LbL thin films to promote wound healing and decrease scar formation.

The Solid Mechanics of Cancer and Strategies for Improved Therapy.

Tumor progression and response to treatment is determined in large part by the generation of mechanical stresses that stem from both the solid and the fluid phase of the tumor. Furthermore, elevated solid stress levels can regulate fluid stresses by compressing intratumoral blood and lymphatic vessels. Blood vessel compression reduces tumor perfusion, while compression of lymphatic vessels hinders the ability of the tumor to drain excessive fluid from its interstitial space contributing to the uniform elevation of the interstitial fluid pressure. Hypoperfusion and interstitial hypertension pose major barriers to the systemic administration of chemotherapeutic agents and nanomedicines to tumors, reducing treatment efficacies. Hypoperfusion can also create a hypoxic and acidic tumor microenvironment that promotes tumor progression and metastasis. Hence, alleviation of intratumoral solid stress levels can decompress tumor vessels and restore perfusion and interstitial fluid pressure. In this review, three major types of tissue level solid stresses involved in tumor growth, namely stress exerted externally on the tumor by the host tissue, swelling stress, and residual stress, are discussed separately and details are provided regarding their causes, magnitudes, and remedies. Subsequently, evidence of how stress-alleviating drugs could be used in combination with chemotherapy to improve treatment efficacy is presented, highlighting the potential of stress-alleviation strategies to enhance cancer therapy. Finally, a continuum-level, mathematical framework to incorporate these types of solid stress is outlined.

Microstructure, mechanical properties, bio-corrosion properties and cytotoxicity of as-extruded Mg-Sr alloys.

In this study, as-extruded Mg-Sr alloys were studied for orthopedic application, and the microstructure, mechanical properties, bio-corrosion properties and cytotoxicity of as-extruded Mg-Sr alloys were investigated by optical microscopy, scanning electron microscopy with an energy dispersive X-ray spectroscopy, X-ray diffraction, tensile and compressive tests, immersion test, electrochemical test and cytotoxicity test. The results showed that as-extruded Mg-Sr alloys were composed of α-Mg and Mg17Sr2 phases, and the content of Mg17Sr2 phases increased with increasing Sr content. As-extruded Mg-Sr alloy with 0.5wt.% Sr was equiaxed grains, while the one with a higher Sr content was long elongated grains and the grain size of the long elongated grains decreased with increasing Sr content. Tensile and compressive tests showed an increase of both tensile and compressive strength and a decrease of elongation with increasing Sr content. Immersion and electrochemical tests showed that as-extruded Mg-0.5Sr alloy exhibited the best anti-corrosion property, and the anti-corrosion property of as-extruded Mg-Sr alloys deteriorated with increasing Sr content, which was greatly associated with galvanic couple effect. The cytotoxicity test revealed that as-extruded Mg-0.5Sr alloy did not induce toxicity to cells. These results indicated that as-extruded Mg-0.5Sr alloy with suitable mechanical properties, corrosion resistance and good cytocompatibility was potential as a biodegradable implant for orthopedic application.