Thermosensitive and biodegradable PCL-based hydrogels: potential scaffolds for cartilage tissue engineering.

Due to a lack of sufficient blood supply and unique physicochemical properties, the treatment of injured cartilage is laborious and needs an efficient strategy. Unfortunately, most of the current therapeutic approaches are, but not completely, unable to restore the function of injured cartilage. Tissue engineering-based modalities are an alternative option to reconstruct the injured tissue. Considering the unique structure and consistency of cartilage tissue (osteochondral junction), it is mandatory to apply distinct biomaterials with unique properties slightly different from scaffolds used for soft tissues. PCL is extensively used for the fabrication of fine therapeutic scaffolds to accelerate the restorative process. Thermosensitive PCL hydrogels with distinct chemical compositions have paved the way for sophisticated cartilage regeneration. This review aimed to collect recent findings regarding the application of PCL in hydrogels blended with natural, synthetic materials in the context of cartilage healing.

Enhancing the function of PLGA-collagen scaffold by incorporating TGF-ß1-loaded PLGA-PEG-PLGA nanoparticles for cartilage tissue engineering using human dental pulp stem cells.

Since cartilage has a limited capacity for self-regeneration, treating cartilage degenerative disorders is a long-standing difficulty in orthopedic medicine. Researchers have scrutinized cartilage tissue regeneration to handle the deficiency of cartilage restoration capacity. This investigation proposed to compose an innovative nanocomposite biomaterial that enhances growth factor delivery to the injured cartilage site. Here, we describe the design and development of the biocompatible poly(lactide-co-glycolide) acid-collagen/poly(lactide-co-glycolide)-poly(ethylene glycol)-poly(lactide-co-glycolide) (PLGA-collagen/PLGA-PEG-PLGA) nanocomposite hydrogel containing transforming growth factor-ß1 (TGF-ß1). PLGA-PEG-PLGA nanoparticles were employed as a delivery system embedding TGF-ß1 as an articular cartilage repair therapeutic agent. This study evaluates various physicochemical aspects of fabricated scaffolds by 1HNMR, FT-IR, SEM, BET, and DLS methods. The physicochemical features of the developed scaffolds, including porosity, density, degradation, swelling ratio, mechanical properties, morphologies, BET, ELISA, and cytotoxicity were assessed. The cell viability was investigated with the MTT test. Chondrogenic differentiation was assessed via Alcian blue staining and RT-PCR. In real-time PCR testing, the expression of Sox-9, collagen type II, and aggrecan genes was monitored. According to the results, human dental pulp stem cells (hDPSCs) exhibited high adhesion, proliferation, and differentiation on PLGA-collagen/PLGA-PEG-PLGA-TGFß1 nanocomposite scaffolds compared to the control groups. SEM images displayed suitable cell adhesion and distribution of hDPSCs throughout the scaffolds. RT-PCR assay data displayed that TGF-ß1 loaded PLGA-PEG-PLGA nanoparticles puts forward chondroblast differentiation in hDPSCs through the expression of chondrogenic genes. The findings revealed that PLGA-collagen/PLGA-PEG-PLGA-TGF-ß1 nanocomposite hydrogel can be utilized as a supportive platform to support hDPSCs differentiation by implementing specific physio-chemical features.

Novel nanocomposite scaffold based on gelatin/PLGA-PEG-PLGA hydrogels embedded with TGF-ß1 for chondrogenic differentiation of human dental pulp stem cells in vitro.

In the current study, a novel nanocomposite hydrogel scaffold comprising of natural-based gelatin and synthetic-based (poly D, L (lactide-co-glycolide) -b- poly (ethylene glycol)-b- poly D, L (lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymer was developed and loaded with transforming growth factor- ß1 (TGF-ß1). Synthesized scaffolds' chemical structure was examined by 1H NMR and ATR-FTIR. Scanning electron microscopy (SEM) confirmed particle size and morphology of the prepared nanoparticles as well as the scaffolds. The morphology analysis revealed a porous interconnected structure throughout the scaffold with a pore size dimension of about 202.05 µm. The swelling behavior, in vitro degradation, mechanical properties, density, and porosity were also evaluated. Phalloidin/DAPI staining was utilized for confirming the extended cytoskeleton of the chondrocytes. Alcian blue staining was conducted to determine cartilaginous matrix sulfated glycosaminoglycan (sGAG) synthesis. Eventually, over a period of 21 days, a real-time RT-PCR analysis was applied to measure the mRNA expression of chondrogenic marker genes, type-II collagen, SOX 9, and aggrecan, in hDPSCs cultured for up to 21 days to study the influence of gelatin/PLGA-PEG-PLGA-TGF-ß1 hydrogels on hDPSCs. The findings of the cell-encapsulating hydrogels analysis suggested that the adhesion, viability, and chondrogenic differentiation of hDPSCs improved by gelatin/PLGA-PEG-PLGA-TGF-ß1 nanocomposite hydrogels. These data supported the conclusion that gelatin/PLGA-PEG-PLGA-TGF-ß1 nanocomposite hydrogels render the features that allow thein vitrofunctionality of encapsulated hDPSCs and hence can contribute the basis for new effective strategies for the treatment of cartilage injuries.

Continuing professional education of Iranian healthcare professionals in shared decision-making: lessons learned.

BACKGROUND: In this study, we sought to assess healthcare professionals' acceptance of and satisfaction with a shared decision making (SDM) educational workshop, its impact on their intention to use SDM, and their perceived facilitators and barriers to the implementation of SDM in clinical settings in Iran. METHODS: We conducted an observational quantitative study that involved measurements before, during, and immediately after the educational intervention at stake. We invited healthcare professionals affiliated with Tabriz University of Medical Sciences, East Azerbaijan, Iran, to attend a half-day workshop on SDM in December 2016. Decisions about prenatal screening and knee replacement surgery was used as clinical vignettes. We provided a patient decision aid on prenatal screening that complied with the International Patient Decision Aids Standards and used illustrate videos. Participants completed a sociodemographic questionnaire and a questionnaire to assess their familiarity with SDM, a questionnaire based on theoretical domains framework to assess their intention to implement SDM, a questionnaire about their perceived facilitators and barriers of implementing SDM in their clinical practice, continuous professional development reaction questionnaire, and workshop evaluation. Quantitative data was analyzed descriptively and with multiple linear regression. RESULTS: Among the 60 healthcare professionals invited, 41 participated (68%). Twenty-three were female (57%), 18 were specialized in family and emergency medicine, or community and preventive medicine (43%), nine were surgeons (22%), and 14 (35%) were other types of specialists. Participants' mean age was 37.51 ± 8.64 years with 8.09 ± 7.8 years of clinical experience. Prior to the workshop, their familiarity with SDM was 3.10 ± 2.82 out of 9. After the workshop, their belief that practicing SDM would be beneficial and useful (beliefs about consequences) (beta = 0.67, 95% CI 0.27, 1.06) and beliefs about capability of using SDM (beta = 0.32, 95% CI -0.08, 0.72) had the strongest influence on their intention of practicing SDM. Participants perceived the main facilitator and barrier to perform SDM were training and high patient load, respectively. CONCLUSIONS: Participants thought the workshop was a good way to learn SDM and that they would be able to use what they had learned in their clinical practice. Future studies need to study the level of intention of participants in longer term and evaluate the impact of cultural differences on practicing SDM and its implementation in both western and non-western countries.

Novel hybrid polyester-polyacrylate hydrogels enriched with platelet-derived growth factor for chondrogenic differentiation of adipose-derived mesenchymal stem cells in vitro.

BACKGROUND: The goal of the present study was to create a new biodegradable hybrid PCL-P (HEMA-NIPAAm) thermosensitive hydrogel scaffold by grafting PNIPAAm-based copolymers with biodegradable polyesters to promote the chondrogenic differentiation of human progenitor cells (adipose-derived stem cells-hASCs) in the presence of the platelet-derived growth factor (PDGF-BB). Different mixture ratios including 50 mmol ε-caprolactone and 10 mmol HEMA (S-1), 30 mmol ε-caprolactone and 10 mmol HEMA (S-2), 10 mmol ε-caprolactone and 30 mmol HEMA (S-3) were copolymerized followed by the addition of NIPAAm. RESULTS: A mild to moderate swelling and wettability rates were found in S-2 group copmpared to the S-1 ans S-3 samples. After 7 weeks, S-2 degradation rate reached ~ 43.78%. According to the LCST values, S-2, reaching 37 °C, was selected for different in vitro assays. SEM imaging showed nanoparticulate structure of the scaffold with particle size dimensions of about 62-85 nm. Compressive strength, Young's modulus, and compressive strain (%) of S-2 were 44.8 MPa, 0.7 MPa, and 75.5%. An evaluation of total proteins showed that the scaffold had the potential to gradually release PDGF-BB. When hASCs were cultured on PCL-P (HEMA-NIPAAm) in the presence of PDGF-BB, the cells effectively attached and flattened on the scaffold surface for a period of at least 14 days, the longest time point evaluated, with increased cell viability rates as measured by performing an MTT assay (p < 0.05). Finally, a real-time RT-PCR analysis demonstrated that the combination of PCL-P (HEMA-NIPAAm) and PDGF-BB promoted the chondrogenesis of hASCs over a period of 14 days by up-regulating the expression of aggrecan, type-II collagen, SOX9, and integrin ß1 compared with the non-treated control group (p < 0.05). CONCLUSION: These results demonstrate that the PCL-P(HEMA-NIPAAm) hydrogel scaffold carrying PDGF-BB as a matrix for hASC cell seeding is a valuable system that may be used in the future as a three-dimensional construct for implantation in cartilage injuries.

Indirect coculture of stem cells with fetal chondrons using PCL electrospun nanofiber scaffolds.

In vitro coculture system provides a powerful tool for tissue engineering. In this study, we evaluated the gene expressions of human adipose-derived stem cells (ASCs) on polycaprolactone (PCL) scaffold in coculture model with fetal chondrons. Electrospun PCL scaffolds (900 nm fiber diameter) were created and human infrapatellar fat pad-adipose-derived stem cells (IPFP-ASCs) were seeded on these scaffolds. Scanning electron microscopy (SEM) showed attachment of human IPFP-ASCs to scaffold. IPFP-ASCs on scaffolds were cocultured with fetal chondrons in transwell. Gene expressions were investigated using real-time polymerase chain reaction (real-time PCR). In comparison with control group, the expression level of collagen type 2 and aggrecan were significantly decreased but Indian Hedgehog(IHH) significantly increased (P < 0.05).These findings may interpreted that IPFP-ASCs seeded on PCL scaffold, in cocultures with fetal chondrons are tending toward osteogenesis rather than chondrogenesis.

Study of chondrogenic potential of stem cells in co-culture with chondrons.

OBJECTIVES: Three-dimensional biomimetic scaffolds have widespread applications in biomedical tissue engineering due to similarity of their nanofibrous architecture to native extracellular matrix. Co-culture system has stimulatory effect on chondrogenesis of adult mesenchymal stem cells. This work presents a co-culture strategy using human articular chondrons and adipose-derived stem cells (ASCs) from infrapatellar fat pad (IPFP) for cartilage tissue production. MATERIALS AND METHODS: Isolated stem cells were characterized by flowcytometry. Electrospun and polycaprolactone (PCL) scaffolds (900 nm fiber diameter) was obtained from Bon Yakhteh (Tehran-Iran) and human infrapatellar fat pad-derived stem cells (IPFP-ASCs) were seeded on them. IPFP-ASCs on scaffolds were co-cultured with articular chondrons using transwell. After 21 day, chondrogenic differentiation of stem cell was evaluated by determining the genes expression of collagen2, aggrecan and Indian hedgehog using real-time RT-PCR. RESULTS: Genes expression of collagen2, aggrecan by IPFP-ASCs did not alter significantly in comparison with control group. Howevers, expression of Indian hedgehog decreased significantly compared to control group (P< 0.05). CONCLUSION: These findings indicate that chondrons obtained from osteoarthritic articular cartilage did not stimulate chondrogenic differentiation of IPFP-ASCs in co-culture.

Clinical Results of Meniscal Repair Using Submeniscal Horizontal Sutures.

BACKGROUND: Parts of the implants placed over the meniscus during meniscal repair can wear down the cartilage in the contact zones and cause chronic synovitis. Placing horizontal sutures under the meniscus may overcome this potential hazard. The purpose of this prospective study was to evaluate the midterm results of arthroscopic meniscal repair using submeniscally placed out-in horizontal sutures. METHODS: One hundred and three meniscal repairs with submeniscal horizontal out-in technique in 103 patients were performed between 2009 and 2012. Our indications for meniscal repair were all longitudinal tear in red-red and red-white zone with acceptable tissue quality. Clinical evaluation included the Tegner and Lysholm knee scores and clinical success was defined as absence of joint-line tenderness, locking, swelling, and a negative McMurray test. RESULTS: The average follow-up was 19 months (range, 14 to 40 months). The time interval from injury to meniscal repair ranged from 2 days to 390 days (median, 96 days). At the end of follow-up, the clinical success rate was 86.5%. Fourteen of 103 repaired menisci (13.5%) were considered failures according to Barrett's criteria. The mean Lysholm score significantly improved from 39.6 preoperatively to 84.5 postoperatively (P<0.001). Eighty five patients (82.5%) had an excellent or good result according to Lysholm knee score. Tegner activity score improved significantly (P<0.01) from an average of 3.4 (range, 2-6) preoperatively to 5.9 (range, 5-8) postoperatively. Statistical analysis showed that age, simultaneous anterior cruciate ligament reconstruction, chronicity of injury did not affect the clinical outcome. CONCLUSION: Our results showed that acceptable midterm results are expected from submeniscal horizontal out-in repair technique. This technique is cheap, safe and has the advantage of avoiding chondral abrasion caused by solid implants and suture materials placed over the meniscus.

Comparison of three skin closure methods in knee mid-anterior incisions.

BACKGROUND: Few clinical trials have studied the functional and cosmetic outcomes using different closure techniques for surgical incisions. Since wound and rupture closure methods may influence the healing process and cosmetic outcome, the present study aims at comparing three different suture techniques. METHODS: In a clinical trial, sixty patients with an anterior cruciate ligament rupture were studied. At the end of the operation and after subcutaneous tissue closure, the skin incision was divided into three equal parts. Each part was randomly sutured using one of three techniques: simple, vertical mattress, or semisubcuticular suture techniques. After six months follow-up, we take a picture of the healed wound in each individual. The cosmetic outcome was rated and evaluated by three Orthopedic Surgeons according to the visual analogue scale (zero to 10). During the study, wounds were followed up for inflammation, infection, or discharges. RESULTS: There were no significant differences between cosmetic results of different suturing methods. The mean and standard deviation of VAS scores for three different observer were 5.62±1.39, 5.62±1.13, 5.65±1.29 in the simple suture; 6.05±1.33, 6.13±1.01, 5.93±1.02 in the vertical mattress technique and 5.72±1.82, 5.81±097 and 5.77±0.99 in the semisubcutaneous method. Overall agreements between observers were weak to moderate. Slight superiority of the semisubcuticular sutures were not statistically significant. CONCLUSIONS: The methods used for suturing an anterior midline incision of the knee does not seem to affect the final cosmetic outcome. The concept of different surgeons from a favorable cosmetic result could totally differ.

Arthroscopic evaluation of the accuracy of clinical examination versus MRI in diagnosing meniscus tears and cruciate ligament ruptures.

BACKGROUND: Magnetic resonance imaging (MRI) of the knee joint has often been regarded as a noninvasive alternative to diagnostic arthroscopy. In day-to-day clinical practice, the MRI scan is routinely used to support the diagnosis for meniscus or ligamentous injuries prior to recommending arthroscopic examination and surgery. On the other hand, rapidly progressing medical technology sometimes obscures the importance of history and physical examination. This study aims to evaluate the accuracy of physical examination and MRI scanning in the diagnosis of knee injury, including meniscus tears and cruciate ligament ruptures. METHODS: In a cross-sectional, descriptive analytical study, 120 patients with knee injury who were candidates for arthroscopy were referred to Tabriz Shohada Hospital during a one-year period. Prior history of arthroscopy or knee surgery was considered as exclusion criteria. Before ordering an MRI and arthroscopy, a thorough physical examination of the affected knee was performed and a preliminary diagnosis made. The results of arthroscopy were considered as the definitive diagnosis, therefore the results of the physical examination and MRI were judged accordingly. RESULTS: Of the 120 evaluated patients with knee injuries, there were 108 males and 12 females with a mean age of 29.13 ± 7.37 (16-54) years. For medial meniscus injuries, clinical examination had an accuracy of 85%, sensitivity of 94.8%, and specificity of 75.8%. Lateral meniscus injuries had the following results: accuracy (85%), sensitivity (70.8%) and specificity (88.5%). Clinical examination of anterior cruciate injuries had an accuracy of 95.8%, sensitivity of 98.6% and specificity of 91.7%. According to MRI results, for medial meniscus injuries there was an accuracy of 77.5%, sensitivity of 84.2%, and specificity of 71.4%. In lateral meniscus injuries, MRI had an accuracy of 85.8%, sensitivity of 56.5% and 92.8% specificity. MRI evaluation of anterior cruciate injuries was 92.5% for accuracy, 98.6% for sensitivity, and 83.3% for specificity. Both clinical examination and MRI were 100% for posterior cruciate injuries. Overall, in isolated injuries, the accuracy of clinical examination was relatively better than with complicated cases. The opposite results were seen for MRI findings in this regard. CONCLUSION: According to our results, both physical examination and MRI scans are very sensitive and accurate in the diagnosis of knee injuries, with a mild preference for physical examination. MRI should be reserved for doubtful cases or complicated injuries.

Association of adult attention deficit/hyperactivity disorder and traffic injuries in tabriz - iran.

OBJECTIVE: Nowadays, it is well known that the attention-deficit/hyperactivity disorder (ADHD) is not confined to children and adolescents. Recent data showed that a considerable portion of the general adult population may be affected by ADHD. On the other hand, the impact of ADHD on driving performance, a major area of adult life, has gained enthusiasm. More recent studies revealed an association between adult ADHD and undesirable driving problems. This study was performed to determine the association between presence of adult ADHD and traffic injuries. METHODS: In this case-control study, in a 13 month period, 140 subjects (70 drivers/riders injured in traffic accidents, and 70 age- and sex-matched non traumatic controls) were selected to participate in the study and were placed in two groups. Subjects with psychiatric comorbidities were excluded. The Conners' Adult ADHD Rating Scale (CAARS) self-report (screening version) was used for screening adult ADHD in both groups. Finally, the occurrence of this condition was compared between the case and control groups. RESULTS: Sixty- nine males and one female were recruited in each group with a mean age of 29.31±9.32 (18-61) years in the case and 29.03±9.07 (range: 18-60) years in the control groups (P > 0.05). Previous history of traffic accident was significantly higher in the case group (15.7% vs. 4.3%, P=0.024). The mean driving time in a day was also significantly higher in the case group. In the case group, the scores of CAARS (the ADHD index, ADHD symptoms total, inattentive subscale and hyperactive/impulsive subscale) were positive (higher than 70) in 4.3, 10, 7.1 and 10 percent of patients respectively. Among the controls, the corresponding proportions were 4.3, 14.3, 8.6 and 8.6 percent respectively. The two groups were comparable for the mentioned rates. CONCLUSION: The results of this study revealed no significant association between ADHD and traffic injuries in Tabriz- Iran.