PCL Group Research Articles

How psychopathy is associated with the level and change of impulsivity in correctional treatment

IntroductionResearch indicates that psychopathy can hinder treatment success and can lead to dropout. Impulsivity is a complex construct that overlaps with psychopathic personality traits and is often targeted in forensic psychotherapy due to its relation to the risk of reoffending.ObjectivesOur aim was to investigate the overlap between psychopathy and impulsivity and the influence of psychopathic traits on change in impulsivity.MethodsWe conducted a pre-post-study for measures of psychopathy and impulsivity in men imprisoned for sexual and non-sexual violent offenses. All participants took part in standardized pre- and post-treatment ratings shortly after admission as well as after an average of 19 months (n=370 for pre-rating, n=168 for post-rating). Psychopathy was measured via the PCL-R, impulsivity with the BIS-15.We calculated two-tailed Pearson correlations for BIS-15 Pre-, Post-, and Change Scores and the PCL-R. In a second step, the BIS-15 pre-post-differences were compared using independent t-Tests, effect sizes were calculated using Cohen’s d (small, medium, and large effect sizes are d = .20, .50, and .80). Further, unpaired t-tests were carried out to compare between participants with lower and higher PCL-R sum scores (median split, mdn= 15.8, M=15.5, SD=7.9).ResultsIn the total population a significant reduction of self assessed impuslivity can be demonstrated for total impulsivity (p<.001, cohens d= .34) nonplanned (p<.001, cohens d= .39) and motor impulsivity (p=.004, cohens d= .23). In both groups, with higher and lower psychopathic traits, a significant reduction in total and nonplannend impulsivity can be seen.While the reduction in total impulsivity was 0.9 points higher in the group with higher psychopathy, the difference was not significant, t(147.8)= -1.1, p = .285. Also, the nonplanned impulsivity was showed a stronger reduction in the high PCL group, though the effect was not significant, t, t(166)= -1.2, p = .243.Table 1.Correlationen between BIS-15 post-ratings and PCL-RPCL-R PCL-R Sum Interpersonal affective lifestyleantisocialBIS-15 prä (n=370)Total Impulsivity.20 **-.14 **.02.34 **.28 **BIS-15 post (n=168)Total Impulsivity.33**.04.20**.35**.36**BIS-15 Change (n=168)Total Impulsivity-.03-.15-.09.07.01Note: * correlation significant für p ≤ .05; ** correlation significant für p ≤ .001.ConclusionsWe demonstrate a significant correlation between psychopathy and impulsivity, especially regarding facets 3 and 4, but also for the sum score. Neither the PCL-R sum core, nor the facets correlate with the change in impulsivity during treatment progress in the STU. In both groups, with higher and lower psychopathy, impulsivity was reduced during therapy but there was no significant difference in the change scores. Our results underline that treatment progress can be achieved also in patients with higher psychopathic traits.Disclosure of InterestNone Declared

Augmented Repair and Regeneration of Critical Size Rabbit Calvaria Defects with 3D Printed Silk Fibroin Microfibers Reinforced PCL Composite Scaffolds

Treatment of critical size defects is quite challenging, often requiring autologous bone grafts for bone regeneration. A massive volume of autologous bone is essential during this process to fill the defect leading to donor site morbidity. Although 3D printed PCL scaffolds are frequently utilised for bone correction procedures, there have been reports of delayed PCL biodegradation and inadequate bone tissue formation. To enhance the regenerative potential, in this study, silk in the form of silk fibroin microfibers are reinforced into the PCL matrix to form the composite. Two silk variations were used: Antheraea mylitta and Bombyx mori, and has been proven to promote cell proliferation, adhesion, and osteogenic potential. This work creates 8 mm critical size defects in a rabbit calvaria model to test for the first time ever the ability of 3D printed PCL-silk scaffolds to regenerate bone tissue. Micro-CT imaging and histological examination performed 6 and 12 weeks after implantation revealed that the PCL-silk scaffold-augmented defects considerably outgrew their PCL-scaffold-only counterparts and the control group in terms of neo-bone formation. By 6 weeks, PCL-silk scaffolds had 47.4–50.3% of bone growth that was twice as high as PCL scaffolds alone (16.7–19.9%). Similarly, by 12 weeks, the PCL-silk group had four times more (80–87.3%) new bone tissue production than the PCL group (18.6–22.4%). The promise of silk fibroin-reinforced PCL biomaterial for pre-clinical and clinical studies for craniofacial reconstructive applications is thus supported by these results.

Exogenous Penicillium camemberti Lipase Preparation Exerts Prebiotic-like Effects by Increasing Cecal Bifidobacterium and Lactobacillus Abundance in Rats

Penicillium camemberti is used in cheese production; however, its health benefits remain to be elucidated. We previously found that supplemental Aspergillus-derived lipase preparation exerts a strong bifidogenic effect in rats fed a high-fat diet. This study investigated the effects of the feeding of a diet containing a 0.2% or 0.4% Penicillium camemberti-derived lipase preparation (PCL) for two weeks on the cecal microbiota in rats. According to 16S rRNA gene sequencing analysis, both PCL supplements significantly (p < 0.05) affected the cecal microbial community. At the genus level, supplemental 0.4% PCL significantly increased the relative abundance of beneficial bacteria such as Bifidobacterium, Lactobacillus, and Collinsella (127-fold, 6-fold, and 193-fold increase, respectively). The abundance of these bacteria in the 0.2% PCL group was between that of the control and 0.4% PCL groups. Notably, the effects of supplemental 0.4% PCL on modulating the abundance of these bacteria matched the effects observed in studies on typical prebiotic oligosaccharides. PICRUSt analysis revealed that PCL supplements significantly modulated the relative abundance of bacterial genes associated with 27 metabolic pathways, some of which were similar to those reported for prebiotic oligosaccharides. This study provides the first evidence indicating that supplemental PCL exerts prebiotic-like effects by modulating the abundance of the gut microbiota.

Peritoneal Protein Clearance Is Associated With Cardiovascular Events but Not Mortality in Peritoneal Dialysis Patients.

IntroductionAssociation of peritoneal protein clearance (Pcl) with outcomes in patients with peritoneal dialysis (PD) is uncertain. Thus, we aimed to investigate its impact on cardiovascular events and all-cause mortality in patients with PD and factors associated with Pcl.MethodsPrevalent patients with PD from January 2014 to April 2015 in the center of Renji Hospital were enrolled. At the time of enrollment, serum and dialysate samples were collected to detect biochemical parameters and Angiopoietin-2-Tie2 system cytokines. Mass transfer area coefficient of creatinine (MTACcr) and Pcl were calculated. Patients were dichotomized into two groups by the median Pcl level (68.5 ml/day) and were followed up prospectively until the end of the study (1 October 2018).ResultsA total of 318 patients with PD [51.2% men, mean age 56.7 ± 14.3 y, median PD duration 31.5 (12.1–57.2) months] were enrolled. Among them, 25.7% were comorbid with diabetes and 28.6% had a history of cardiovascular disease (CVD). After being followed up for up to 43.9 (24.2–50.3) months, 63 had developed cardiovascular events, and 81 patients were died. Among them, the high Pcl group had occurred 39 cardiovascular events and 51 deaths, and the low Pcl group had 24 cardiovascular events and 30 deaths. Kaplan-Meier analysis showed that both the occurrence of cardiovascular events and all-cause mortality were increased in patients with high Pcl. However, after adjusting for important confounders and serum Angiopoietin-2 (Angpt-2) level, Pcl was still an independent risk factor for cardiovascular events [hazard ratio (HR) = 1.006 (1.000–1.012), p = 0.038] but not mortality. On multivariate regression analysis, serum albumin, MTACcr, and body mass index (BMI) were found to be independently associated with Pcl.ConclusionHigh Pcl is an independent risk factor for cardiovascular events but not all-cause mortality. The prediction of cardiovascular events by Pcl was independent of serum Angpt-2.

Regeneration of Bone Defects in a Rabbit Femoral Osteonecrosis Model Using 3D-Printed Poly (Epsilon-Caprolactone)/Nanoparticulate Willemite Composite Scaffolds.

Steroid-associated osteonecrosis (SAON) is a chronic disease that leads to the destruction and collapse of bone near the joint that is subjected to weight bearing, ultimately resulting in a loss of hip and knee function. Zn2+ ions, as an essential trace element, have functional roles in improving the immunophysiological cellular environment, accelerating bone regeneration, and inhibiting biofilm formation. In this study, we reconstruct SAON lesions with a three-dimensional (3D)-a printed composite made of poly (epsilon-caprolactone) (PCL) and nanoparticulate Willemite (npW). Rabbit bone marrow stem cells were used to evaluate the cytocompatibility and osteogenic differentiation capability of the PCL/npW composite scaffolds. The 2-month bone regeneration was assessed by a Micro-computed tomography (micro-CT) scan and the expression of bone regeneration proteins by Western blot. Compared with the neat PCL group, PCL/npW scaffolds exhibited significantly increased cytocompatibility and osteogenic activity. This finding reveals a new concept for the design of a 3D-printed PCL/npW composite-based bone substitute for the early treatment of osteonecrosis defects.

3D-Printed Barrier Membrane Using Mixture of Polycaprolactone and Beta-Tricalcium Phosphate for Regeneration of Rabbit Calvarial Defects.

Background: Polycarprolactone and beta tricalcium phosphate (PCL/β-TCP) are resorbable biomaterials that exhibit ideal mechanical properties as well as high affinity for osteogenic cells. Aim: Objective of this study was to evaluate healing and tissue reaction to the PCL/β-TCP barrier membrane in the rabbit calvaria model for guided bone regeneration. Materials and Methods: The PCL/β-TCP membranes were 3D printed. Three circular defects were created in calvaria of 10 rabbits. The three groups were randomly allocated for each specimen: (i) sham control; (ii) PCL/β-TCP membrane (PCL group); and (iii) PCL/β-TCP membrane with synthetic bone graft (PCL-BG group). The animals were euthanized after two (n = 5) and eight weeks (n = 5) for volumetric and histomorphometric analyses. Results: The greatest augmented volume was achieved by the PCL-BG group at both two and eight weeks (p < 0.01). There was a significant increase in new bone after eight weeks in the PCL group (p = 0.04). The PCL/β-TCP membrane remained intact after eight weeks with slight degradation, and showed good tissue integration. Conclusions: PCL/β-TCP membrane exhibited good biocompatibility, slow degradation, and ability to maintain space over eight weeks. The 3D-printed PCL/β-TCP membrane is a promising biomaterial that could be utilized for reconstruction of critical sized defects.

Bone Regeneration Assessment of Polycaprolactone Membrane on Critical-Size Defects in Rat Calvaria.

Biomaterials for use in guided bone regeneration (GBR) are constantly being investigated and developed to improve clinical outcomes. The present study aimed to comparatively evaluate the biological performance of different membranes during the bone healing process of 8 mm critical defects in rat calvaria in order to assess their influence on the quality of the newly formed bone. Seventy-two adult male rats were divided into three experimental groups (n = 24) based on the membranes used: the CG—membrane-free control group (only blood clot, negative control), BG—porcine collagen membrane group (Bio-Guide®, positive control), and the PCL—polycaprolactone (enriched with 5% hydroxyapatite) membrane group (experimental group). Histological and histometric analyses were performed at 7, 15, 30, and 60 days postoperatively. The quantitative data were analyzed by two-way ANOVA and Tukey’s test (p < 0.05). At 7 and 15 days, the inflammatory responses in the BG and PCL groups were significantly different (p < 0.05). The PCL group, at 15 days, showed a large area of newly formed bone. At 30 and 60 days postoperatively, the PCL and BG groups exhibited similar bone healing, including some specimens showing complete closure of the critical defect (p = 0.799). Thus, the PCL membrane was biocompatible, and has the potential to help with GBR procedures.

The directing effect of mono primary and secondary amine group substituted cyclotriphosphazenes on the reactions of the disodium salt of tetraethylene glycol

This study examines how the mono primary and mono secondary amine groups on the cyclotriphosphazene ring will direct the tetraethylene glycol (a flexible diol) and which of the five active P-Cl bonds in the structure will be preferred in detail. Isopropylaminopentachlorocyclotriphosphazene (1a) and dimethylaminopentachloro-cyclotriphosphazene (1b) were reacted with the disodium salt of tetraethylene glycol in THF solution at 1:1 mole ratio. Four new cyclotriphosphazene derivatives; 1,3-mono ansa (2a), mono spiro (3b), trans 3,5-mono ansa (4b) and cis 3,5-mono ansa (5b) were isolated. The structures of these compounds were characterized by elemental analysis, mass spectrometry (MALDI-TOF), 1H and 31P NMR spectroscopy. Additionally, the structure of compounds 2a, 4b and 5b were illuminated by single crystal X-Ray diffraction technique. In the reaction of compound 1a with the disodium salt of tetraethylene glycol, it was determined that the ONa+ group was primarily replaced the chlorine atom of the PCl(NHR) group (via proton abstraction/chloride elimination), whereas compound 1b gave a nucleophilic substitution reaction with chlorine atoms on other phosphorus atoms (via SN2 and SN1 reaction mechanisms, respectively).

An injectable high-conductive bimaterial scaffold for neural stimulation

Neurological recovery is difficult due to limited axonal regeneration and the limitations of autograft therapeutics in repairing peripheral nerve defects. Alternatively, the implantable nerve guidance conduit represents a promising approach for the nerve regeneration of especially large injury gaps. Herein, we presented an easily injectable and highly conductive, tissue engineering scaffold for supporting nerve cells growth and promoting neural differentiation. The ultra-flexible conductive scaffold was prepared by the combination of PCL-based micro-grid via melt electrowriting (MEW) with a nanolayer of gold via sputter coating, which shows good mechanical properties (including high flexibility and recoverability) and high conductivity. The conductive interface acts as a bridge for electrical signal transmission between nerve cells under electrical stimulation, which significantly enhances neural differentiation and improves the neurite outgrowth. Specifically, compared with the PCL group, the neurite length of the 50 Au-PCL and 80 Au-PCL groups increased by nearly 10 and 15 times respectively, after 10 days of culture without ES treatment. Furthermore, as the increase of Au coating thickness, the promotion of the ES effect was further improved. The 80 Au-PCL group showed the highest average neurite length and neurite number per cell compared with PCL (11 times), 20 Au-PCL (9 times), 50Au-PCL (3 times) after ES treatment for 5 days (one hour per day). Overall, our Au-PCL bimaterial scaffold is a promising nerve repair material because of its suitable injectability, high conductivity, biocompatibility, and powerful ability to promote neural stimulation.

Cell-free 3D wet-electrospun PCL/silk fibroin/Sr2+ scaffold promotes successful total meniscus regeneration in a rabbit model

Considering the intrinsic poor self-healing capacity of meniscus, tissue engineering has become a new direction for the treatment of meniscus lesions. However, disturbed by mechanical stability and biocompatibility, most meniscus implants fail to relieve symptoms and prevent the development of osteoarthritis. The goal of this study was to develop a potential meniscal substitute for clinical application. Here, silk fibroin with good mechanical performance and biocompatibility, and strontium ion acting as bioactive factor, were incorporated with Ɛ-Polycaprolactone to fabricate a meniscus scaffold (SP-Sr). By the wet-electrospun method, the 3D SP-Sr provided suitable pore size (100–200 μm) and enough mechanical support (61.6 ± 2.9 MPa for tensile modulus and 0.11 ± 0.03 MPa for compressive modulus). Moreover, after addition of Sr2+, the SP-Sr seeded by rabbit adipose tissue-derived stromal cells (rADSCs) showed the highest secretion with 2.61- and 2.98-fold increase in collagen and aggrecan, respectively, compared with SF/PCL group. And the extracellular matrix related genes expression in SP-Sr also showed upregulation results. Particularly, the expression of the collagen II gene, which played a crucial role in the formation of meniscal inner avascular region, showed a 9-fold increase in SP-Sr compared with pure PCL group. Furthermore, the MRI results of SP-Sr implanted in rabbits with total meniscectomy for 6 months demonstrated effective prevention of meniscus extrusion and relieving joint space narrowing compared with meniscectomy group. And the effects of cartilage protection and delaying osteoarthritis development were confirmed by Pathological examination. Especially, after 6-month implantation, the neo-menisci showed similar structural constituent and mechanical performance. Statement of significanceMeniscus regeneration faces great challenge due to the meniscus having limited healing potential owing to its anisotropic structure, its hypocellularity and hypovascularity. The present tissue engineering solutions have failed to maintain the biological function for meniscus reconstruction in vivo because of fragile and poor biocompatible materials, leading to long-term joint degeneration. The goal of this study was to develop a meniscal substitute potential for clinical application. Here, silk fibroin and strontium were incorporated with Ɛ-Polycaprolactone by wet-electrospinning method to fabricate a meniscus scaffold (SP-Sr). The 6-month implantation results revealed that SP-Sr scaffold was effective in preventing meniscus extrusion, cartilage protection and delaying osteoarthritis development, and the regenerated menisci showed similar structural constituent and mechanical performance.

Designing of energetic miktoarm A2B2 star‐shaped polymer by means of click chemistry and ROP techniques

Novel A2B2‐type energetic miktoarm star‐shaped copolymers composed of two PGN arms and two PCL arms was synthesized by the combination of ring‐opening polymerization (ROP) and “click” chemistry. Initially, diazido end‐functionalized two‐arm PGN, (PGN)2‐(N3)2, was synthesized by ROP of glycidyl nitrate monomers. Subsequently, (PGN)2‐(PCL)2 was obtained from the click reaction between diazido end‐functionalized (PGN)2‐(N3)2 polymers and propargyl‐terminated poly(ε‐caprolactone) (PTPCL). This star copolymer solves problems of PCL (lake of energy) and PGN (low Tg). The Fourier‐transform infrared (FT‐IR), 1H nuclear magnetic resonance (NMR), and gel permeation chromatography (GPC) studies revealed that (PGN)2‐(PCL)2 was successfully obtained. The thermal behavior of star polymer was investigated by thermogravimetric analysis (TGA) and derivative thermogravimetry. The results show that (PGN)2‐(PCL)2 decomposed at two stages. The first stage is seen at 212.6°C which related to degradation of –ONO2 group and second stage attributed to degradation of PCL group which is seen at 346.1°C.

Periosteum-derived mesenchymal progenitor cells in engineered implants promote fracture healing in a critical-size defect rat model.

An attractive alternative to bone autografts is the use of autologous mesenchymal progenitor cells (MSCs) in combination with biomaterials. We compared the therapeutic potential of different sources of mesenchymal stem cells in combination with biomaterials in a bone nonunion model. A critical-size defect was created in Sprague-Dawley rats. Animals were divided into six groups, depending on the treatment to be applied: bone defect was left empty (CTL); treated with live bone allograft (LBA); hrBMP-2 in collagen scaffold (CSBMP2 ); acellular polycaprolactone scaffold (PCL group); PCL scaffold containing periosteum-derived MSCs (PCLPMSCs ) and PCL containing bone marrow-derived MSCs (PCLBMSCs ). To facilitate cell tracking, both MSCs and bone graft were isolated from green fluorescent protein (GFP)-transgenic rats. CTL group did not show any signs of healing during the radiological follow-up (n=6). In the LBA group, all the animals showed bone bridging (n=6) whereas in the CSBMP2 group, four out of six animals demonstrated healing. In PCL and PCLPMSCs groups, a reduced number of animals showed radiological healing, whereas no healing was detected in the PCLBMSCs group. Using microcomputed tomography, the bone volume filling the defect was quantified, showing significant new bone formation in the LBA, CSBMP2 , and PCLPMSCs groups when compared with the CTL group. At 10weeks, GFP positive cells were detected only in the LBA group and restricted to the outer cortical bone in close contact with the periosteum. Tracking of cellular implants demonstrated significant survival of the PMSCs when compared with BMSCs. In conclusion, PMSCs improve bone regeneration being suitable for mimetic autograft design.

Femoral Component Rotation in Total Knee Arthroplasty: A Comparison Between Transepicondylar Axis and Posterior Condylar Line Referencing

BackgroundProper rotational alignment of the femoral component is critical for a successful total knee arthroplasty (TKA). Controversy remains regarding the optimal intraoperative reference to determine femoral component rotation. MethodsThirty-one patients who underwent magnetic resonance imaging of a TKA between April 2008 and November 2015 were retrospectively reviewed. A single surgeon performed the TKA using a posterior condylar angle of 3° (PCA group) or surgical transepicondylar axis (TEA group) to determine femoral component rotation. The hip-knee-ankle angle and the tibial plateau-tibial shaft angle (TPTSA) were measured on full-length x-rays, and the rotation of the femoral component was measured as compared to the TEA on magnetic resonance imaging (negative values indicate internal rotation). ResultsThe median measured rotational deviation of the femoral component from the TEA was significantly higher in the PCA group than in the TEA group (−3.8 ± 2.9° and −1.4 ± 1.9°, respectively) (P = .02). When knees with preoperative varus and neutral alignment were evaluated, the median measured rotational deviation of the femoral component was significantly higher in the fixed PCL group than in the TEA group (−3.4 ± 3.3° and −0.61 ± 1.3°, respectively) (P = .04). Linear regression used to evaluate the relationship between the TPTSA and femoral component rotational deviation from the TEA revealed similar near zero slopes (P = .90); however, the Y intercepts in the TEA group were significantly higher than the PCA group (−2.8 ± 0.7 and −5.5 ± 1.1, respectively) (P = .007). ConclusionThe use of the surgical TEA as an intraoperative rotational reference is more reliable than the PCA in valgus, varus, and neutrally aligned knees independent from the magnitude of the TPTSA.

Biomechanical Function of Anterior Cruciate Ligament Remnants: Quantitative Measurement With a 3-Dimensional Electromagnetic Measurement System

To evaluate quantitatively the biomechanical function of anterior cruciate ligament (ACL) remnants in patients with ACL injuries. Anterior tibial translation (ATT) with KT-1000 and during the Lachman test with an electromagnetic measurement system (EMS) and tibial acceleration during the pivot shift test with EMS were measured. A total of 121 unilateral ACL injuries were examined. ACL remnants were morphologically classified as being attached to the posterior cruciate ligament (PCL group), to the roof of the intercondylar notch (RIN group), to the lateral wall of the intercondylar notch (LWIN group), or as having no substantial remnants (NONE group). Partial ACL tears were excluded. ATT was measured using KT-1000. ATT during the Lachman test and tibial acceleration during the pivot shift test were measured using EMS. ACL remnant patterns were as follows: PCL group, 27 knees; RIN group, 34 knees; LWIN group, 27 knees; and NONE group, 33 knees. The ATT side-to-side difference in LWIN group (3.4 ± 0.7mm) by KT-1000 was significantly smaller than the RIN (5.7 ± 1.0mm) and NONE groups (5.9 ± 1.0mm)(P < .05). The ATT side-to-side difference during the Lachman test was significantly smaller in the LWIN group (5.3 ± 1.2mm) than the PCL (8.6 ± 1.4mm), RIN (8.5 ± 1.2mm), and NONE groups (7.6 ± 1.0mm)(P < .05). Tibial accelerations were 2.0 ± 0.4, 1.7 ± 0.2, 1.9 ± 0.2, and 1.8 ± 0.3m/s(2) in the PCL, RIN, LWIN, and NONE groups, respectively. There were no significant differences among groups. ACL remnants attached to the lateral wall of the intercondylar notch partially contributed to anterior-posterior stability but did not contribute to dynamic knee stability. These findings suggest that ACL remnants attached to nonanatomic insertion sites do not contribute significantly to knee stabilization. Level III, diagnostic study of nonconsecutive patients.

Uniformly-dispersed nanohydroxapatite-reinforced poly(ε-caprolactone) composite films for tendon tissue engineering application

Regeneration of injuries at tendon-to-bone interface (TBI) remains a challenging issue due to the complex tissue composition involving both soft tendon tissues and relatively hard bone tissues. Tissue engineering using polymeric/ceramic composites has been of great interest to generate scaffolds for tissue's healing at TBI. Herein, we presented a novel method to blend polymers and bioceramics for tendon tissue engineering application. A homogeneous composite comprising of nanohydroxyapatite (nHA) particles in poly(ε-caprolactone) (PCL) matrix was obtained using a combination of solvent and mechanical blending process. X-ray diffraction analysis showed that the as-fabricated PCL/nHA composite film retained phase-pure apatite and semi-crystalline properties of PCL. Infrared spectroscopy spectra confirmed that the PCL/nHA composite film exhibited the characteristics functional groups of PCL and nHA, without alteration to the chemical properties of the composite. The incorporation of nHA resulted in PCL/nHA composite film with improved mechanical properties such as Young's Modulus and ultimate tensile stress, which were comparable to that of the native human rotator tendon. Seeding with human tenocytes, cells attached on the PCL/nHA composite film, and after 14days of culturing, these cells could acquire elongated morphology without induced cytotoxicity. PCL/nHA composite film could also result in increased cell metabolism with prolonged culturing, which was comparable to that of the PCL group and higher than that of the nHA group. All these results demonstrated that the developed technique of combining solvent and mechanical blending could be applied to fabricate composite films with potential for tendon tissue engineering applications.

In vivo regeneration of complex cartilage/bone defect using biomimetic scaffolds

Event Abstract Back to Event In vivo regeneration of complex cartilage/bone defect using biomimetic scaffolds Yingying Du1, Haoming Liu1, Jianglin Wang2, Qin Yang1, Jiaqi Shuang1 and Shengmin Zhang1 1 Huazhong University of Science and Technology, Advanced Biomaterials and Tissue Engineering Center, China 2 UniversityofOklahoma, Department of Chemistry and Biochemistry, United States Introduction: Due to the complex structure of the osteochondral interface, highly bioinspired scaffolds with continuous gradients in properties are needed as potential repair grafts [1],[2]. In this work, a novel multilayer scaffold with continuous HA gradient was well designed for osteochondral repair and fabricated by microsphere-based selective laser sintering (SLS), using PCL and HA/PCL microspheres. Materials and Methods: PCL and HA/PCL composite microspheres were prepared using modified S/O/W emulsion solvent evaporation method [3]. A cylindrical scaffold of 4 mm in diameter and 2.8 mm in thickness was designed via Pro/Engineer 3D modeling software and fabricated by SLS, with the HA content continuously increasing from 0 to 30%, from top to bottom. Rat bone mesenchymal stem cells (MSCs) were used to evaluate the in vitro cytocompatibility. A critical sized osteochondral defect in rabbit was created to evaluate the in vivo repair, using micro-CT and histological analysis. Results and Discussion: The novel multilayer scaffolds with interconnected pores and moderate mechanical property were demonstrated to be suitable for cell adhesion and proliferation in vitro. For osteochondral repair in vivo, the subchondral bone was considered as the key foundation for successful cartilage repair. In our study, the microspheres-based HA/PCL bony phase effectively facilitated the new bone formation compared to the PCL group. After 6 weeks, new bone has formed at the bottom of the implanted multilayer scaffold. After 12 weeks, abundant new bone filled the subchondral area with obvious vascularization. Moreover, the new bone integrated well with the adjacent tissue, providing a strong mechanical supporting for the defect area. The rapid and sufficient regeneration of subchondral bone may further significantly improve the repair of cartilage. Completely different cartilage repair was observed for the two kinds of scaffold. The defect implanted with the multilayer scaffold was repaired with zonal hyaline cartilage, however, inferior repair with fibrous tissue and fibrocartilage in the chondral area was observed in the PCL scaffold. Conclusion: Combining the microsphere-based SLS technology and the strategy of continuous gradient scaffold, the current study designed and fabricated a novel multilayer scaffold with continuous HA gradient, with demonstrated great potential for osteochondral repair.

Concentrations of progesterone, a metabolite of PGF2α, prolactin, and luteinizing hormone during development of idiopathic persistent corpus luteum in mares

In experiment 1, daily blood samples were available from Days 0 to 20 (Day 0 = ovulation) in mares with an interovulatory interval (IOI, n = 5) and in mares that developed idiopathic persistent corpus luteum (PCL, n = 5). The PCL was confirmed by maintenance of progesterone (P4) concentration until end of the experiment (Day 20). Significant interactions of group and day revealed the novel findings that luteinizing hormone (LH) was lower (P < 0.05) in the PCL group than that in the IOI group on Days 0 to 4, and prolactin was lower (P < 0.05) on Days 1, 4, 6, and 7. In experiment 2, treatment with a gonadotropin-releasing hormone antagonist (n = 6) significantly reduced LH on Days 1 to 6 compared with the controls (n = 6) but did not support the hypothesis that low LH during the postovulatory period increases the frequency of PCL. In experiment 3, P4, PGFM (a PGF2α metabolite), and prolactin concentrations on Days 12 to 20 from 2 reported experiments were combined to increase the number of mares with an IOI (n = 11) or a PCL (n = 11). An abrupt and complete decrease in P4 (luteolysis) began on Day 13 in the IOI group compared with a gradual and partial P4 decline after Day 12 in the PCL group. Concentrations of PGFM and prolactin were lower (P < 0.05) in the PCL group than those in the IOI group on the day at the end of the most pronounced decrease in P4. The PCL mares were subgrouped into those with an abrupt but incomplete P4 decrease (partial luteolysis; n = 5) at the expected time and those without partial luteolysis (n = 6). There were no significant differences between the 2 subgroups in concentrations of PGFM and prolactin, but on a tentative basis (P < 0.10), the concentration of PGFM seemed more focused on the day of the most pronounced decrease in P4 in the subgroup with partial luteolysis. Results for PCL compared with IOI indicated (1) postovulatory LH and prolactin were lower, (2) treatment to reduce postovulatory LH did not increase the incidence, and (3) both PGFM and prolactin were lower on the day of the most pronounced decrease in P4.

Evaluation of biodegradable polymer conduits – poly(l-lactic acid) – for guiding sciatic nerve regeneration in mice

Polymeric biomaterials are often used for stimulating nerve regeneration. Among different conduits, poly(lactide acid) – PLA polymer is considered to be a good substrate due to its biocompatibility and resorbable characteristics. This polymer is an aliphatic polyester which has been mostly used in biomedical application. It is an organic compound with low allergenic potential, low toxicity, high biocompatibility and predictable kinetics of degradation. In this study we fabricated and evaluated a PLA microporous hollow fiber as a conduit for its ability to bridge a nerve gap in a mouse sciatic nerve injury model. The PLA conduit was prepared from a polymer solution, throughout extrusion technique. The left sciatic nerve of C57BL/6 mouse was transected and the nerve stumps were placed into a resorbable PLA (PLA group) or a PCL conduit (PCL group), n=5 each group. We have also used another group in which the nerves were repaired by autograft (autograft group, n=5). Motor function was analyzed according to sciatic functional index (SFI). After 56days, the regenerated nerves were processed for light and electron microscopy and morphometric analyses were performed. A quantitative analysis of regenerated nerves showed significant increase in the number of myelinated fibers and blood vessels in animals that received PLA conduit. The PLA group exhibited better overall tissue organization compared to other groups. Presenting well-organized bundles, many regenerating clusters composed of preserved nerve fibers surrounded by layers of compacted perineurium-like cells. Also the SFI revealed a significant improvement in functional recovery. This work suggests that PLA conduits are suitable substrate for cell survival and it provides an effective strategy to be used to support axonal growth becoming a potential alternative to autograft.

Development of a Large Animal Model of Osteochondritis Dissecans of the Knee: A Pilot Study.

Background:Treatment of osteochondritis dissecans (OCD) of the knee is challenging, and evidence for stage-dependent treatment options is lacking. Basic science approaches utilizing animal models have provided insight into the etiology of OCD but have yet to produce a reliable and reproducible large animal model of the disease on which to test new surgical strategies.Purpose/Hypotheses:The purpose of this study was to develop an animal model featuring an OCD-like lesion in terms of size, location, and International Cartilage Repair Society (ICRS) grading. The hypothesis was that surgical creation of an osteochondral defect followed by placement of a barrier between parent bone and progeny fragment would generate a reproducible OCD-like lesion.Study Design:Controlled laboratory study.Methods:Bilateral osteochondral lesions were created in the medial femoral condyles of 9 Yucatan minipigs. After lesion creation, a biodegradable membrane was interposed between the progeny and parent bone. Five different treatment groups were evaluated at 2 weeks: a control with no membrane (ctrl group; n = 4), a slowly degrading nanofibrous poly(∊-caprolactone) membrane (PCL group; n = 4), a fenestrated PCL membrane with 1.5-mm holes covering 25% of surface area (fenPCL group; n = 4), a collagen membrane (Bio-Gide) (CM group; n = 3), and a fenestrated CM (fenCM group; n = 3). Five unperturbed lateral condyles (1 from each treatment group) served as sham controls. After euthanasia on day 14, the lesion was evaluated by gross inspection, fluoroscopy, micro–computed tomography (micro-CT), and histology. To quantify changes between groups, a scoring system based on gross appearance (0-2), fluoroscopy (0-2), and micro-CT (0-6) was established. Micro-CT was used to quantify bone volume per total volume (BV/TV) in a defined region surrounding and inclusive of the defect.Results:The no scaffold group showed healing of the subchondral bone at 2 weeks, with continuity of subchondral bone elements. Conversely, condyles treated with PCL or CM showed substantial remodeling, with loss of bone in both the progeny fragment and surrounding parent bone. When these membranes were fenestrated (fenPCL and fenCM groups), bone loss was less severe. Histological analysis showed no integration in the cartilage layer in any treatment group, while fibrous tissue formed between the parent and progeny fragments. Micro-CT showed significant differences in mean BV/TV between the PCL (27.4% ± 2.3%) and the sham (47.7% ± 1.4%) or no scaffold (54.9% ± 15.1%) groups (P < .01 and P < .05, respectively). In addition, a significant difference in bone loss was evident between the PCL and fenPCL groups (mean BV/TV, 46.6% ± 15.2%; P < .05), as well as between the PCL and fenCM (mean BV/TV, 50.9% ± 3.5%) and fenPCL groups (P < .01). Grading by 6 blinded reviewers using an OCD scoring system with 3 subcategories showed a significant difference between control and PCL groups.Conclusion:This study successfully developed a large animal model of OCD-like lesions in the knee joint of Yucatan minipigs. The lesions generated matched characteristics of an ICRS grade 3 OCD lesion in humans. These findings set the stage for ongoing model refinement as well as exploration of novel interventional therapies to restore function and bone and cartilage patency in individuals affected by this rare but significant disease.Clinical Relevance:This developed model will serve as a platform on which to further investigate the natural course as well as emerging treatment options for OCD.

Theoretical approach to the structural, electronic, and morphological properties of poly(ɛ-caprolactone) grafted polypyrroles

Poly(ɛ-caprolactone) grafted polypyrroles (PPy-g-PCL) are an important member of hairy-rod copolymers which have many industrial applications. PPy-g-PCL cooligomers were studied for their electronic, structural and morphological properties by density functional theory (DFT), molecular dynamics and mesoscale dynamics simulation methods. The band gaps of the cooligomers were calculated at the B3LYP/6-31g(d,p) level by varying the grafting position of PCL group. UV spectra was studied by time-dependent DFT methods. The solubility parameters and interaction parameters between the PCL and PPy were calculated via molecular dynamics simulations. The morphological behaviors were studied by the molecular dynamics and dissipative particle dynamics (DPD) methods to understand the role of rigidity of polypyrrole backbone, the chain lengths of PPy and PCL and the incompatibility of the polymers on the formation of layered phase domains observed experimentally for high weight percentages of PCL side chains. Open image in new window