Tissue responses to novel tissue engineering biodegradable cryogel scaffolds: an animal model

Biodegradable macroporous cryogels with highly open and interconnected pore structures were produced from dextran modified with oligo L-lactide bearing hydroxyethylmethacrylate (HEMA) end groups in moderately frozen solutions. Tissue responses to these novel scaffolds were evaluated in rats after dorsal subcutaneous implantation, iliac submuscular implantation, auricular implantation, or in calvarial defect model. In no case, either necrosis or foreign body reaction was observed during histological studies. The cryogel scaffolds integrated with the surrounding tissue and the formation of a new tissue were accompanied with significant ingrowth of connective tissue cells and new blood vessels into the cryogel. The tissue responses were significantly lower in auricular and calvarial implantations when compared with the subcutanous and the submuscular implantations. The degradation of the scaffold was slower in bone comparing to soft tissues. The biodegradable cryogels are highly biocompatible and combine extraordinary properties including having soft and elastic nature, open porous structure, and very rapid and controllable swelling. Therefore, the cryogels could be promising candidates for further clinical applications in tissue regeneration.     

Mobile vs. fixed meniscal bearing in total knee replacement: a randomised radiostereometric study

52 knees scheduled for a total knee arthroplasty were randomised to either a fixed or a mobile polyethylene bearing. The design was identical in all parts. The knee systems used were the Rotaglide Total Knee System (RTK) ® and the Nuffield Total Knee System (NTK)®, both from the same manufacturer (Corin Medical Ltd., UK). All knees implanted were uncemented. The patients were followed for 2 years clinically and with radiostereometric analyses to assess migration over time and inducible displacement of the tibial component. Separate analysis of the mobility of the tibial insert in the knees with a mobile bearing was also made. The migration measured with RSA between the 1st and 2nd year expressed as maximum total point motion (MTPM) might predict the risk of loosening of the implant.

There were no differences between the groups regarding clinical outcome (HSS Knee score), migration or inducible displacement during the 2 years follow-up. The movement between the tibial tray and the mobile meniscal insert expressed as maximum total point motion (MTPM) was 6.8±3.3 mm at the 1st year follow-up.     

Determining the stress biomarker profile in patients undergoing total knee replacement and the relationship with outcome at 12 months

BackgroundTotal knee replacement (TKR) is the commonest joint arthroplasty procedure worldwide. Despite excellent outcomes, some studies have reported dissatisfaction in up to 20% of patients.There is evidence of an association between the biochemical stress response to surgery and outcomes. The objective of this study is to describe the stress biomarker profile for TKR, and correlate this with patient outcomes.MethodsA prospective cohort study of 50 patients undergoing primary TKR was conducted. Serum IL-6, TNF-α, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were measured immediately pre- and post-operatively, and on Days 1 and 3. Follow-up questionnaires including the Oxford Knee Score (OKS) and EuroQol five dimensions (EQ-5D) were completed at 12-months.Univariate analysis was completed using a linear regression model (p < 0.05).ResultsSerum IL-6, NLR, and PLR all increased to Day 1 post-operatively, and decreased by Day 3. TNF-α values increased across all time points.Statistical analysis found a significant negative correlation (r = ? 0.414; p = 0.005) between pre-operative IL-6 and 12-month OKS. There was a significant positive correlation between pre-operative NLR and 12 month OKS (r = 0.272; p = 0.039) and 12 month EQ5D (r = 0.268; p = 0.043).ConclusionThis is the first study to describe the biochemical stress response to TKR. The results raise the potential for a pre-operative risk stratification tool for patients based on IL-6 and NLR measurements.Further research should be conducted to explore the underlying mechanisms involved, and investigate interventions to reduce pre-operative physiological stress with a view to improving post-operative outcomes.     

Maternal nutrient restriction in sheep: hypertension and decreased nephron number in offspring at 9 months of age

Pregnant ewes were fed either a 50% nutrient-restricted (NR; n = 8) or a control 100% (C; n = 8) diet from day 28 to day 78 of gestation (dGA; term = 150 dGA). Lambs were born naturally, and fed to appetite throughout the study period. At 245 ± 1 days postnatal age (DPNA), offspring were instrumented for blood pressure measurements, with tissue collection at 270 DPNA. Protein expression was assessed using Western blot, glomerulus number determined via acid maceration and hormone changes by radioimmunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA). NR lambs had higher mean arterial pressure (MAP; 89.0 ± 6.6 versus 73.4 ± 1.6 mmHg; P < 0.05), fewer renal glomeruli (57.8 ± 23.8 versus 64.6 ± 19.3 × 10⁴; P < 0.05), increased expression of angiotensin converting enzyme (ACE) in the renal cortex (942 ± 130 versus 464 ± 60 arbitrary pixel units (apu); P < 0.03), and increased angiotensin II receptor AT2 expression in the renal medulla (63.3 ± 12.1 versus 19.5 ± 44.2 × 10⁴ apu; P < 0.03). All data are presented as mean ± s.e.m. The present data indicate that global maternal nutrient restriction (50%) during early to mid-gestation impairs renal nephrogenesis, increases MAP, and alters expression of AT2 and ACE without an associated change in birth weight. These data demonstrate the existence of a critical window of fetal susceptibility during early to mid-gestation that alters kidney development and blood pressure regulation in later life.     

Collagen morphology in human meniscal attachments: A SEM study

Qualitative analysis of meniscal attachments from five human knees was completed using scanning electron microscopy (SEM). In addition, quantitative analysis to determine the collagen crimping angle and length in each attachment was done. Morphological differences were revealed between the distinct zones of the attachments from the meniscus transition to the bony insertion. Collagen fibers near to the meniscus appeared inhomogeneous in a radial cross-section view. The sheath surrounding the fibers seemed loose compared with the membrane wrapping around the fibers in the menisci. The midsubstance of human meniscal attachments was composed of collagen fibers running parallel to the longitudinal axis, with a few fibers running obliquely, and others transversely. The bony insertion showed that the crimping pattern vanishes as the collagen fibers approach the fibrocartilagenous enthesis. There were no differences between attachments for crimping angle or length. Collagen crimping angles for all attachments were similar with values of approximately 22°. Crimp length values tended to be smaller for the medial attachments (MA: 4.76 ± 1.95 μm; MP: 3.72 ± 2.31 μm) and higher for the lateral (LA: 6.49 ± 2.34 μm, LP: 6.91 ± 2.29 μm). SEM was demonstrated to be an effective method for revealing the morphology of fibrous connective tissue. The data of collagen fiber length and angle found in this study will allow for better development of microstructural models of meniscal attachments. This study will help to better understand the relation between the morphology and the architecture of collagen and the mechanical behavior of meniscal attachments.     

Osteochondral defect repair using a novel tissue engineering approach: sheep model study.

Porous calcium polyphosphate (CPP) constructs of desired density were formed by sintering CPP powders. Articular cartilage was formed on these constructs in cell culture over an 8-week period with the resulting cartilage layer forming on the CPP surface and within the near surface pores thereby mechanically anchoring the cartilage to the CPP. The biphasic constructs so formed were implanted in sheep femoral condyle sites and left for short-term periods (3 to 4 months) or longer periods (9 months). Implant fixation within the condyle sites was achieved through bone ingrowth into the inferior CPP pores. The properties and characteristics of the as-in vitro-formed, short- and long-term implanted tissues were compared. The results indicated that such implants might be useful for repair of small subchondral defects.     

Role of inflammation and ischemia after implantation of xenogeneic pulmonary valve conduits: histological evaluation after 6 to 12 months in sheep

OBJECTIVE: Commercially available biological heart valve prostheses undergo degenerative changes, which finally lead to complete destruction. Here we evaluate the role of inflammation and ischemia after implantation of xenogeneic heart valve conduits (XPC) generated by novel concepts of tissue engineering. METHODS: Acellularized (a-)XPC and autologus re-seeded (s-)XPC were implanted into sheep. Samples were taken as follows: after acellularization (n = 2), after re-seeding (n = 2), 6 months (seeded/non-seeded: n = 3/5), 9 months (n = 2/5), and 12 months (n = 3/2) post implantation. Five native porcine conduits served as control. Using histological methods, samples were evaluated for pathological changes and existence/density of microvessels. RESULTS: Prior to implantation a-XPC were completely free of cells. Six months after implantation, leaflets and pulmonary arteries of s-XPC and a-XPC showed good endothelial surface coverage. Microvessel density within the myocardial cuffs and pulmonary vessel walls were comparable to control in all grafts. However, 6, 9 and 12 months after implantation pathological severe microvessel ingrowth, calcification and cellular infiltrations were observed on a-XPC and s-XPC valves, whereas myocardial cuffs and XPC-artery walls showed only mild degenerative alterations. CONCLUSIONS: Inflammatory reactions play a pivotal role in the degeneration of a-XPC and s-XPC. Thus, since ischemia seems to have little or no influence on this process, inflammation inductive factors should be the center of interest.     

Tissue engineering of biphasic cartilage constructs using various biodegradable scaffolds: an in vitro study

Biological restoration of osteochondral defects requires suitable subchondral support material that also allows the induction of hyaline cartilage tissue. Biphasic implants consisting of pre-fabricated neocartilage and an underlying biodegradable osteoconductive base may meet these requirements. Here we explore various candidate biodegradable support materials onto which neo-cartilage was produced in vitro. Porcine chondrocytes were seeded in a closed and static bioreactor with a base of biomaterial consisting of either poly-L-lactide [P(L)LA], poly-d,l-lactide [P(D,L)LA] or Collagen-hydroxyapatite [Col-HA] and were cultured for 15 weeks. Viable neo-cartilage was produced on each biomaterial with differing amounts of cellular colonisation. P(D,L)LA breakdown was more rapid and uneven among the three biomaterials, leading to constructs of irregular shape. Little or no breakdown or chondrocyte colonisation was evident in P(L)LA. Col-HA constructs were superior in terms of viability, implant morphology and integration between neo-cartilage and biomaterial. These results indicate that our reported system has potential for producing biphasic implants that may be adequate for the repair of osteochondral defects.     

Porous polymer implant for repair of meniscal lesions: a preliminary study in dogs

Artificial meniscal lesions extending into the avascular part of the meniscus, which do not heal by any other means, were repaired by suturing either a porous polymer implant or a synovial flap into the defect. The implant guided the ingrowth of vascular repair tissue into the defect. This fibrous tissue later on transformed into fibrocartilage. Reconstruction with a synovial flap was not successful. It appeared that healing can be achieved by implantation of a porous polymer implant in a large number of cases. Future research will be aiming at improvement of the results of meniscal repair and application of this type of polymer for repair of cartilage defects.     

A porous polymer scaffold for meniscal lesion repair--a study in dogs

Meniscal lesions often occur in the avascular area of the meniscus with little chance of spontaneous repair. An access channel in the meniscal tissue can function as an entrance for ingrowing repair tissue from the vascular periphery of the meniscus to the lesion in the avascular zone which again induced healing of the lesion. Implantation of a porous polymer in a full-thickness access channel induced healing. However, a better integration between meniscal tissue and the implant might be achieved with the combination of the newly developed porous polymers and a modified surgical technique. This might improve meniscal lesion healing and the repair of the access channel with neo-meniscal tissue. Longitudinal lesions were created in the avascular part of 24 canine lateral menisci and a partial-thickness access channel was formed to connect the lesion with the meniscal periphery. In 12 menisci, the access channel was left empty (control group), while in the remaining 12 menisci the polymer implant was sutured into the access channel. Repair of the longitudinal lesions was achieved with and without polymer implantation in the partial-thickness access channel. Polymer implants induced fibrous ingrowth with cartilaginous areas, which resembled neo-meniscal tissue. Implantation did not prevent articular cartilage degeneration.     

A 12 months follow-up study of depression among nursing-home patients in Norway

BackgroundDepression is common in nursing-home patients and is often of chronic nature.AimsTo examine the prevalence, incidence and the persistence rates of clinically significant depressive symptoms, and their risk factors among nursing-home patients.DesignA 12 months follow-up study.MethodsA sample of 902 randomly selected nursing-home patients was assessed using the Cornell Scale, the Clinical Dementia Rating Scale, the Self-Maintenance Scale and a measurement of physical health. Information was collected from the patients' records. Clinically significant depression was defined as 8+ on the Cornell Scale.ResultsAt 12 months 231 had died, and depression was together with higher age, worse physical health, poor function in activities of daily living, higher CDR score and cancer a significant predictor of death (0.03). The prevalence of depression was 21.2% at baseline and follow-up, incidence rate was 14.9% and persistence rate was 44.8%. Predictors of depression at 12 months were: high Cornell score at baseline (p < 0.001), a shorter stay in a nursing home (0.011) and use of antidepressants (p = 0.050); for incident depression: higher Cornell score at baseline (p = 0.019), a shorter stay (p = 0.002) and higher CDR score (p = 0.003); for persistent depression: higher Cornell score at baseline (0.011), use of anxiolytics (p = 0.045) and not being married (p = 0.037).ConclusionThe incidence and persistence rates of clinical significant depressive symptoms are high in nursing-home patients. A higher score on Cornell Scale at baseline and a shorter stay in a nursing home were predictors for both incidence and persistence of clinically significant depressive symptoms.     

Risk factors for wheeze in the last 12 months in preschool children

Most children with asthma develop their symptoms before the age of 5 years and many preschool wheezers continue to wheeze in the early school years. It is thus important to investigate the factors that predispose young children to wheeze. The objective of this study was to investigate the relevant environmental and family influences on recent wheeze (wheeze within the last 12 months) in preschool children. A cross-sectional study was conducted in five primary health clinics in the district of Kota Bharu from April to October 1998. Nurses from these clinics distributed Bahasa Malaysia questionnaires containing questions on asthma symptoms, environmental risk factors, family's social status and family history of atopy and wheeze to preschool children aged 1-5 years during their home visits. The respondents were parent(s) or carer(s) of the children. A total of 2,524 (87.7%) complete questionnaires were available for analysis of risk factors. One hundred and fifty six (6.2%) children had current wheeze. Significant risk factors associated with current wheeze were a family history of asthma (O.R. = 6.36, 95% C.I. = 4.45-9.09), neonatal hospital admission (O.R. = 2.38, 95% C.I. = 1.51 - 3.75), and a maternal (O.R. = 2.12, 95% C.I. = 1.31-3.41) or paternal (O.R. = 1.52, 95% C.I. = 0.95-2.43) history of allergic rhinitis. Among environmental factors examined, namely, household pets, carpeting in bedroom, use of fumigation mats, mosquito coils and aerosol insect repellents, maternal and paternal smoking, and air conditioning, none were associated with an increased risk of wheeze. In conclusion, the strongest association with current wheeze was a family history of asthma. Also significant were neonatal hospital admission and a history of allergic rhinitis in either the mother or father. None of the environmental factors studied were related to current wheeze in preschool children.     

North Wales randomized controlled trial of cognitive behaviour therapy for acute schizophrenia spectrum disorders: outcomes at 6 and 12 months

BACKGROUND: Recent reviews of randomized controlled trials have concluded that cognitive behaviour therapy (CBT) is effective, as an addition to standard care, in the treatment of people suffering from schizophrenia. Most of the trials have been conducted with stabilized out-patients. The aim of this trial was to evaluate the effectiveness of CBT for in-patients suffering acute psychotic episodes, when delivered under conditions representative of current clinical practice. METHOD: Consecutive admissions meeting criteria were recruited. After screening, 43 were assigned at random to a treatment-as-usual (TAU) control group and 47 were assigned to TAU plus CBT. At baseline, 6 months and 12 months, patients were rated on symptoms and social functioning. CBT (maximum 25 sessions) began immediately after baseline assessment. RESULTS: The CBT group gained greater benefit than the TAU group on symptoms and social functioning. A larger proportion of the CBT group (60%) than the TAU group (40%) showed reliable and clinically important change, and none of them (v. 17%) showed reliable deterioration compared with baseline. CONCLUSIONS: CBT for patients suffering acute psychotic episodes can produce significant benefits when provided under clinically representative conditions.     

Tissue engineering auricular reconstruction: in vitro and in vivo studies

Although investigators have demonstrated that neocartilage can be constituted in a predetermined shape and in complex three-dimensional structures, such as a human ear, by using cell transplantation on polymer constructs, many unsolved problems still remain. The crucial issues for auricular tissue engineering consisted of optimal cell culture environment, choice of polymers, behavior of chondrocytes, study of cell-polymer constructs in an acceptable animal model, and long-term structural integrity. Here we describe our tissue engineering approaches for auricular reconstruction including auricular scaffold fabrication, in vitro chondrogenesis, in vivo immunocompromized xenograft and immunocompetent autologous animal models, and long-term follow-up. Though many current obstacles regarding auricular tissue engineering still exist, we demonstrate techniques of auricular scaffold fabrication with promising in vitro and in vivo neocartilage formation, optimal selection and application of animal models, and, to the best of our knowledge, the first report of different biodegradable biomaterial trials and the longest in vivo results (10 months) for auricular tissue engineering.     

Tissue response to porous high density polyethylene as a three-dimensional scaffold for bone tissue engineering: An experimental study

High density polyethylene (HDPE) is a synthetic biomaterial used as a three-dimensional scaffold for bone defect reconstruction. Reports differ with regard to its biological response, particularly its osteoconductive capacity. The aim of the present work was to histologically and histomorphometrically evaluate tissue response to porous HDPE. An in vivo study was conducted in rat tibia to evaluate osteogenic capacity, angiogenesis, inflammatory response, and the presence of multinucleated giant cells 14 and 60?days post-biomaterial implantation. Histological examination 14?days post-implantation showed fibrovascular tissue inside pores and on the surface of porous HDPE, acute inflammatory response, scant multinucleated giant cells (MNGCs), and lamellar bone in contact with the biomaterial. An increase in the proportion of lamellar bone tissue, no inflammatory response, and a decrease in the number of MNGCs were observed at 60?days. The histomorphometric study showed a significant time-dependent increase both in the area of bone tissue formed in contact with the porous HDPE (14d: 24.450?±?11.623 µm² vs. 60d: 77.104?±?26.217 µm², p?<?0.05) and in the percentage of bone tissue in contact with the porous HDPE (osseointegration). A significant decrease in the number of MNGCs was also observed at 60?days post-implantation. Porous HDPE showed adequate osteoconductive properties, and only caused an initial inflammatory response. Although this biomaterial has traditionally been used juxtaosseoulsy, its adequate osteoconductive properties broaden the scope of its application to include intraosseous placement.