How will early onset scoliosis surgery affect my child's future as a young adult? A follow-up study using patient-reported outcome measures.

PURPOSE: Using patient-reported outcome measures (PROMs), this study was undertaken to determine how well patients with early onset scoliosis (EOS) fare in adulthood. METHODS: Among eight healthcare centers, 272 patients (≥ 18 years) surgically managed for EOS (≥ 5 years) completed the Scoliosis Research Society (SRS)-22r, Functional Assessment of Chronic Illness Therapy-10 (FACIT-Dyspnea-10), and Short Form (SF)-12. Functional and demographic data were collected. RESULTS: The response rate was 40% (108/272). EOS etiologies were congenital (45%), neuromuscular (20%), idiopathic (20%) syndromic (11%), and unknown (4%). All patients scored within normal limits on the FACIT-Dyspnea-10 pulmonary (no breathing aids, 78%; no oxygen, 92%). SF-12 physical health scores and most SRS-22r domains were significantly decreased (p < 0.05 and p < 0.001, respectively) compared with normative values. SF-12 and SRS-22r mental health scores (MHS) were lower than normative values (p < 0.05 and p < 0.02, respectively). Physical health PROMs varied between etiologies. Treatment varied by etiology. Patients with congenital EOS were half as likely to undergo definitive fusion. There was no difference between EOS etiologies in SF-12 MHS, with t scores being slightly lower than normative peers. CONCLUSION: Good long-term physical and social function and patient-reported quality of life were noted in surgically managed patients. Patients with idiopathic EOS physically outperformed those with other etiologies in objective and PROM categories but had similar MHS PROMs. Compared to normative values, EOS patients demonstrated decreased long-term physical capacity, slightly lower MHS, and preserved cardiopulmonary function. LEVEL OF EVIDENCE: Level IV Case Series.

Microwave Ablation of the Pig Growth Plate: Proof of Concept for Minimally Invasive Epiphysiodesis.

BACKGROUND: Different surgical methods for epiphysiodesis of limb length discrepancy (LLD) have been described. Although these methods are variably effective, they are associated with morbidity (pain and limp) and potential complications. Microwave ablation is a less-invasive opportunity to halt growth by selectively destroying the growth plate via thermal energy to treat LLD in children. QUESTIONS/PURPOSES: In this proof-of-concept study using an in vivo pig model, we asked: (1) What is the durability of response 2 to 4 months after microwave ablation of the tibial growth plate as measured by length and angulation of the tibia via a CT scan? (2) Was articular cartilage maintained as measured by standard histologic staining for articular cartilage viability? METHODS: To develop an in vivo protocol for microwave ablation, we placed microwave antennas adjacent to the proximal tibia growth plate in the cadaveric hindlimbs of 18 3-month-old pigs. To determine the suitable time, we varied ablation from 90 to 270 seconds at 65-W power settings. After sectioning the tibia, we visually assessed for discoloration (implying growth plate destruction) that included the central growth plate but did not encroach into the epiphysis in a manner that could disrupt the articular surface. Using this information, we then performed microwave ablation on three live female pigs (3.5 to 4 months old) to evaluate physiologic changes and durability of response. A postprocedure MRI was performed to ensure the intervention led to spatial growth plate alterations similar to that seen in cadavers. This was followed by serial CT, which was used to assess the potential effect on local bone and growth until the animals were euthanized 2 to 4 months after the procedure. We analyzed LLD, angular deformity, and bony deformity using CT scans of both tibias. The visibility of articular cartilage was compared with that of the contralateral tibia via standard histologic staining, and growth rates of the proximal tibial growth plate were compared via fluorochrome labeling. RESULTS: Eighteen cadaveric specimens showed ablation zones across the growth plate without visual damage to the articular surface. The three live pigs did not exhibit changes in gait or require notable pain medication after the procedure. Each animal demonstrated growth plate destruction, expected limb shortening (0.8, 1.2, and 1.5 cm), and bony cavitation around the growth plate. Slight valgus bone angulation (4º, 5º, and 12º) compared with the control tibia was noted. No qualitatively observable articular cartilage damage was encountered from the histologic comparison with the contralateral tibia for articular cartilage thickness and cellular morphology. CONCLUSION: A microwave antenna placed into a pig's proximal tibia growth plate can slow the growth of the tibia without apparent pain and alteration of gait and function. CLINICAL RELEVANCE: Further investigation and refinement of our animal model is ongoing and includes shorter ablation times and comparison of dynamic ablation (moving the antennae during the ablation) as well as static ablation of the tibia from a medial and lateral portal. These refinements and planned comparison with standard mechanical growth arrest in our pig model may lead to a similar approach to ablate growth plates in children with LLD.

Identifying Factors that Determine Effectiveness of Delivery Agents in Biolistic Delivery Using a Library of Amine-Containing Molecules.

Biolistic transfection is a popular and versatile tool for plant transformation. A key step in the biolistic process is the binding of DNA to the heavy microprojectile using a delivery agent, usually a positively charged molecule containing amine groups. Currently, the choice of the commercial delivery agent is mostly limited to spermidine. In addition, the detailed delivery mechanism has not been reported. To help broaden the selection of the delivery agent and reveal the fundamental mechanisms that lead to high delivery performance, a library of amine-containing molecules was investigated. A double-barrel biolistic delivery device was utilized for testing hundreds of samples with much-improved consistency. The performance was evaluated on onion epidermis. The binding and release of DNA were measured via direct high-performance liquid chromatography analysis. This study shows that the overwhelming majority of the amine library performed at the same level as spermidine. To further interpret these results, correlations were performed with thousands of molecular descriptors generated by chemical modeling. It was discovered that the overall charge is most likely the key factor to a successful binding and delivery. Furthermore, even after increasing the amount of the DNA concentration 50-fold to stress the binding capacity of the molecules, the amines in the library continued to deliver at a near identical level while binding all the DNA. The increased DNA was also demonstrated with a Cas9 editing test that required a large amount of DNA to be delivered, and the result was consistent with the previously determined amine performance. This study greatly expands the delivery agent selection for biolistic delivery, allowing alternatives to a commercial reagent that are more shelf-stable and cheaper. The library also offers an approach to investigate more challenging delivery of protein and CRISPR-Cas via the biolistic process in the future.

Buffering the Fear of COVID-19: Social Connectedness Mediates the Relationship between Fear of COVID-19 and Psychological Wellbeing.

Social connections are crucial for an individual's health, wellbeing, and overall effective functioning. During the COVID-19 pandemic, one major preventative effort for reducing the spread of COVID-19 involved restricting people's typical social interactions through physical distancing and isolation. The current cross-sectional study, conducted during the COVID-19 pandemic, explored the relationship among fear of COVID-19, social connectedness, resilience, depressive symptomologies, and self-perceived stress. Participants (N = 174) completed an anonymous, online questionnaire, and results indicated that social connectedness mediated the relationship between fear of COVID-19 and psychological wellbeing. In contrast, the relationship between fear of COVID-19 and psychological wellbeing was not mediated by resilience. These findings highlight the important role that social connections and resilience play in buffering against negative psychological wellbeing outcomes, especially during a pandemic.

Nordic Walking for Overweight and Obese People: A Systematic Review and Meta-Analysis.

BACKGROUND: Nordic walking (NW) is a potentially beneficial exercise strategy for overweight and obese people. To date, no reviews have synthesized the existing scientific evidence regarding the effects of NW on this population. This systematic review and meta-analysis aimed to identify the characteristics, methodological quality, and results of the investigations that have studied the effects of NW in overweight and obese individuals. METHODS: Six electronic databases were searched up to June 2019 for studies that examined the effects of NW on people with a body mass index ≥ 25 kg/m2. The methodological quality of the included randomized controlled trials was retrieved from the physiotherapy evidence database or evaluated using the physiotherapy evidence database scale. RESULTS: Twelve studies were included in the review. The investigations were mostly good-to-fair methodological quality. NW groups had a significant improvement on parameters such as fasting plasma glucose, abdominal adiposity, and body fat compared with the baseline, but no significant improvements were found when compared with control groups. CONCLUSIONS: NW can potentially lead to improvements in parameters related to major health outcomes in overweight and obese people. The lack of control for confounding variables in the analyzed studies prevents further elaboration on its potential benefits.

Trevor's disease of the distal radioulnar joint in two children with achondroplasia.

Two children with achondroplasia who developed an abnormal bony outgrowth at the distal radioulnar joint (DRUJ), indistinguishable from an osteochondroma on histology, but the radiographic appearance, location, and asymmetry suggested the rare diagnosis of dysplasia epiphysealis hemimelica (DEH or "Trevor's disease"). One child experienced symptomatic relief with surgical excision and one was observed clinically due to lack of significant symptoms. These are the first presented cases of DEH in achondroplasia, both affecting the DRUJ. Due to the infrequency of DEH, more research is needed to better understand the potential connection to achondroplasia. For management, we suggest shared surgical decision making based on symptoms.

Fisioterapia para la congelación de la marcha en la enfermedad de Parkinson: revisión sistemática y metaanálisis / Physiotherapy for freezing of gait in Parkinson's disease: a systematic review and meta-analysis

INTRODUCCIÓN: La congelación de la marcha (CDM) es uno de los síntomas más graves asociados con la enfermedad de Parkinson (EP). El tratamiento fisioterapéutico podría ser una estrategia efectiva para su tratamiento, pero no se ha realizado ninguna revisión sistemática al respecto. OBJETIVO: Identificar las características, la calidad metodológica y los principales resultados de los estudios que han analizado los efectos de las intervenciones fisioterapéuticas en CDM hasta la fecha, mediante la realización de una revisión sistemática y un metaanálisis. PACIENTES Y MÉTODOS: Se realizaron búsquedas en cuatro bases de datos electrónicas para encontrar ensayos controlados aleatorizados que proporcionaran información con respecto a los efectos de cualquier tipo de tratamiento fisioterapéutico sobre la CDM. La calidad metodológica de las investigaciones se evaluó mediante la escala PEDro. RESULTADOS: Se identificaron 12 estudios para su inclusión en el análisis cualitativo y cuatro ensayos controlados aleatorizados se incluyeron en el metaanálisis final. La calidad de los ensayos fue generalmente buena. Las modalidades de fisioterapia que incluían señales fueron más efectivas para tratar la CDM que los enfoques de fisioterapia tradicionales. El metaanálisis indicó que las intervenciones fisioterapéuticas tuvieron un impacto significativamente mayor sobre la CDM que las comparaciones de control. CONCLUSIONES: El tratamiento fisioterapéutico, especialmente las modalidades que incluyen señales visuales y auditivas, debe prescribirse a los pacientes con EP con CDM. Se necesitan estudios futuros que incluyan pacientes con EP con deterioro cognitivo y herramientas de medición objetiva de la CDM para completar la evidencia científica existente

INTRODUCTION: Freezing of gait (FOG) is one of the most severe symptoms associated with Parkinson's disease (PD). Physiotherapy treatment could be an effective strategy for treating FOG, but no systematic review has been carried out in this regard. AIM:To identify the characteristics, methodological quality, and main outcomes of the studies that have analyzed the effects of physiotherapy interventions in FOG up to date, by performing a systematic review and a meta-analysis. PATIENTS AND METHODS: Four electronic databases were searched in order to find randomized controlled trials that provided information regarding the effects of any kind of physiotherapy treatment on FOG. The methodological quality of the included investigations was assessed by means of the PEDro scale. RESULTS: Twelve studies were identified for inclusion into the qualitative analysis, with four randomized controlled trials included in the final meta-analysis. The quality of the trials was generally good. Those physiotherapy modalities including cues were more effective for treating FOG than traditional physiotherapy approaches. The meta-analysis indicated that physiotherapy interventions had a significantly greater impact on FOG than control comparisons. CONCLUSIONS: Physiotherapy treatment, especially those modalities including visual and auditory cueing, should be prescribed to PD patients with FOG. Future studies including PD patients with cognitive impairment and FOG objective measurement tools are need to complete the existing scientific evidence

Aerobic, resistance, and mind-body exercise are equivalent to mitigate symptoms of depression in older adults: A systematic review and network meta-analysis of randomised controlled trials.

Background: Exercise has been identified as an allied health strategy that can support the management of depression in older adults, yet the relative effectiveness for different exercise modalities is unknown. To meet this gap in knowledge, we present a systematic review and network meta-analysis of randomised controlled trials (RCTs) to examine the head-to-head effectiveness of aerobic, resistance, and mind-body exercise to mitigate depressive symptoms in adults aged ≥ 65 years. Methods: A PRISMA-NMA compliant review was undertaken on RCTs from inception to September 12 th, 2019. PubMed, Web of Science, CINAHL, Health Source: Nursing/Academic Edition, PsycARTICLES, PsycINFO, and SPORTDiscus were systematically searched for eligible RCTs enrolling adults with a mean age ≥ 65 years, comparing one or more exercise intervention arms, and which used valid measures of depressive symptomology. Comparative effectiveness was evaluated using network meta-analysis to combine direct and indirect evidence, controlling for inherent variation in trial control groups. Results: The systematic review included 82 RCTs, with 69 meeting eligibility for the network meta-analysis ( n = 5,379 participants). Pooled analysis found each exercise type to be effective compared with controls (Hedges' g = -0.27 to -0.51). Relative head-to-head comparisons were statistically comparable between exercise types: resistance versus aerobic (Hedges' g = -0.06, PrI = -0.91, 0.79), mind-body versus aerobic (Hedges' g = -0.12, PrI = -0.95, 0.72), mind-body versus resistance (Hedges' g = -0.06, PrI = -0.90, 0.79). High levels of compliance were demonstrated for each exercise treatment. Conclusions: Aerobic, resistance, and mind-body exercise demonstrate equivalence to mitigate symptoms of depression in older adults aged ≥ 65 years, with comparably encouraging levels of compliance to exercise treatment. These findings coalesce with previous findings in clinically depressed older adults to encourage personal preference when prescribing exercise for depressive symptoms in older adults. Registration: PROSPERO CRD42018115866 (23/11/2018).

Exercise for Nonagenarians: A Systematic Review.

BACKGROUND: Physical exercise has been identified as a health promotion strategy for the oldest old. However, scientific evidence regarding the benefits of exercise on nonagenarians is scarce. This systematic review aimed to evaluate the characteristics and methodological quality of investigations that have examined the effects of physical exercise on nonagenarians. METHODS: A systematic review and evidence synthesis were conducted. The MEDLINE/PubMed, CINAHL, Scopus, SPORTDiscus, and Cochrane Library were systematically searched up to November 2018. Investigations were included if they tested the effects of an exercise intervention on people 90 years or older. The methodological quality of the randomized controlled trials was evaluated using the PEDro scale. Quality appraisal tools developed by the National Heart, Lung and Blood Institute were used to evaluate the uncontrolled and observational investigations. RESULTS: Three randomized controlled trials, 1 retrospective study, 2 case reports, and 1 single-subject A-B design met the eligibility criteria. The methodological quality scores obtained from the scales ranged from poor to good. Most interventions were based on muscular strengthening, balance exercises, or a combination of both. No adverse effects were registered. In general, exercise showed a significant impact on muscular strength, while mixed effects were found regarding gait and balance. Pooled analyses indicated that interventions had significant improvements in global lower body functioning (standardized mean difference, SMD = 0.47; 95% confidence interval = 0.04, 0.90; P < .01). CONCLUSIONS: Exercise is a feasible therapy for nonagenarians, which can lead to improvements in physical functioning. Future research should focus on the effects of aerobic interventions, as well as the impact that exercise has on the cognitive functioning of nonagenarians.

Comparative effectiveness of three exercise types to treat clinical depression in older adults: A systematic review and network meta-analysis of randomised controlled trials.

BACKGROUND: Few studies have directly compared the effects of different exercise therapies on clinical depression in older adults. Thus, we conducted a systematic review and network meta-analysis of current evidence from randomised controlled trials (RCTs) to compare the effectiveness of three major exercise types (aerobic, resistance, and mind-body exercise) in clinically depressed older adults. METHODS: We followed PRISMA-NMA guidelines and searched databases for eligible RCTs (inception - September 12th, 2019). RCTs were eligible if they included clinically depressed adults aged >65 years, implemented one or more exercise therapy arms using aerobic, resistance, or mind-body exercise, and assessed depressive symptoms at baseline and follow-up using a validated clinical questionnaire. RESULTS: A network meta-analysis was performed on 15 eligible RCTs comprising 596 participants (321 treatment and 275 controls), including aerobic (n = 6), resistance (n = 5), and mind-body (n = 4) exercise trials. Compared with controls, mind-body exercise showed the largest improvement on depressive symptoms (g = -0.87 to -1.38), followed by aerobic exercise (g = -0.51 to -1.02), and resistance exercise (g = -0.41 to -0.92). Notably, there were no statistically significant differences between exercise types: aerobic versus resistance (g = -0.10, PrI = -2.23, 2.03), mind-body versus aerobic (g = -0.36, PrI = -2.69, 1.97), or mind-body versus resistance (g = -0.46, PrI = -2.75, 1.83). CONCLUSIONS: These findings should guide optimal exercise prescription for allied health professionals and stakeholders in clinical geriatrics. Notably, clinically depressed older adults may be encouraged to self-select their preferred exercise type in order to achieve therapeutic benefit on symptoms of depression. In coalition with high levels of compliance, these data provide encouraging evidence for the antidepressant effect of either aerobic, resistance, or mind-body exercise as effective treatment adjucts for older adults presenting with clinical depression.

Exercise, Mood, Self-Efficacy, and Social Support as Predictors of Depressive Symptoms in Older Adults: Direct and Interaction Effects.

BACKGROUND: Depression is a chronic condition that affects up to 15% of older adults. The healthogenic effects of regular exercise are well established, but it is still unclear which exercise-related variables characterise the antidepressant effects of exercise. Thus, the purpose of this study was to examine the extent to which exercise-related variables (exercise behaviour, exercise-induced mood, exercise self-efficacy, and social support) can predict depressive symptoms in a cohort of community-dwelling older adults. METHODS: This study employed a cross-sectional analysis of questionnaire data from a sample of 586 community-dwelling older Australians aged 65 to 96 years old. Participants completed the Center for Epidemiologic Studies Depression Scale, modified CHAMPS Physical Activity Questionnaire for Older Adults, Four-Dimension Mood Scale, Self-Efficacy for Exercise Scale, and Social Provisions Scale - Short Form. Bivariate correlations were performed, and hierarchical multiple regression was subsequently used to test the regression model. RESULTS: Exercise behaviour, exercise-induced mood, exercise self-efficacy, and social support were all negatively associated with depressive symptoms (r = -0.20 to -0.56). When the variables were entered as predictors into the hierarchical multiple regression model, social support was the strongest predictor of depressive symptoms (ß = -0.42), followed by exercise-induced mood (ß = -0.23), and exercise self-efficacy (ß = -0.07). Exercise behaviour did not explain any additional variance in depressive symptoms. A modest interaction effect was also observed between exercise-induced mood and social support. CONCLUSION: These findings indicate that social support is the strongest predictor of depressive symptomology in community-dwelling older adults, particularly when combined with positive exercise-induced mood states. When addressing the needs of older adults at risk of depression, healthcare professionals should consider the implementation of exercise programmes that are likely to benefit older adults by improving mood, enhancing self-efficacy, and building social support.

Benefits of Pilates in Parkinson's Disease: A Systematic Review and Meta-Analysis.

Pilates may be a beneficial method of exercise for people with Parkinson's disease (PD). However, no studies have critically reviewed the scientific evidence in this regard. The purpose of this study was to conduct a systematic review and meta-analysis on the effectiveness of Pilates as a rehabilitation strategy for PD. A systematic search of the electronic databases PubMed, PEDro, Scopus, and SPORTDiscus was conducted to identify studies related to the effect of Pilates on PD. The search timeframe ranged from the inception of each database to March 2019. The search resulted in the identification of four randomized controlled trials (RCTs) and four non-RCT studies. The methodological quality of the investigations ranged from poor to fair. The descriptive analysis of the eight investigations showed that Pilates resulted in beneficial effects on fitness, balance and functional autonomy. A subsequent meta-analysis on the four RCTs indicated that Pilates was more effective than traditional training programmes in improving lower limb function. Pilates can be safely prescribed for people with mild-to-moderate PD. Preliminary evidence indicates that its practice could have a positive impact on fitness, balance and physical function. Its benefits on lower-body function appear to be superior to those of other conventional exercises. Future randomized studies with greater samples are needed to confirm these observations.

The Effect of Microporous Polysaccharide Hemospheres on Wound Healing and Scarring in Wild-Type and db/db Mice.

BACKGROUND: Hemostasis, the initial phase of wound healing, sets the stage for tissue repair. Microporous polysaccharide hemosphere powder (MPH) is an FDA-approved hemostatic agent that may impact the wound-healing process. OBJECTIVE: This study examined the role of MPH in murine wild-type and diabetic (db/db) wound-healing models and a foreign body response scarring model. METHODS: The powder was topically applied to excisional wounds in wild-type C57BL/6 mice and db/db mice. The effect of MPH on scarring was evaluated by applying it to the expanded polytetrafluoroethylene tube implantation model. RESULTS: In wild-type mice, topically applied MPH increased epithelial thickness. Levels of α-smooth muscle actin (α-SMA) were decreased in MPH-treated wild-type wounds, whereas Rho-associated protein kinase 2 (ROCK2) and transforming growth factor ß levels were increased. In db/db mice, topical wound MPH application decreased epithelial thickness and delayed wound closure. The db/db wounds displayed an increased collagen index. The ROCK2 was increased in a similar manner to wild-type mice, whereas α-SMA and transforming growth factor ß levels were decreased. The MPH-treated expanded polytetrafluoroethylene tube mice showed increased α-SMA levels and depressed ROCK2 levels. There were no changes in histologic parameters of the foreign body response. CONCLUSIONS: The results suggest that MPH does not adversely impact wound healing in wild-type mice, both topically and around implants, but prolongs time to closure and diminishes thickness in db/db wounds. The MPH application alters contractile proteins in all wound models. These changes could have downstream effects on the wound healing process, and further investigation into the use of MPH in altered or impaired states of wound healing is warranted.

Building Materials from Colloidal Nanocrystal Arrays: Preventing Crack Formation during Ligand Removal by Controlling Structure and Solvation.

Crack-free, ligand-free, phase-pure nanostructured solids, using colloidal nanocrystals as precursors, are fabricated by a scalable and facile approach. Films produced by this approach have conductivities comparable to those of bulk crystals over more than 1 cm (1.370 S cm-1 for PbS films).

Biostable electrospun microfibrous scaffolds mitigate hypertrophic scar contraction in an immune-competent murine model.

Burn injuries in the United States account for over one million hospital admissions per year, with treatment estimated at four billion dollars. Of severe burn patients, 30-90% will develop hypertrophic scars (HSc). In this study, we evaluate the impact of an elastomeric, randomly-oriented biostable polyurethane (PU) scaffold on HSc-related outcomes. In vitro, fibroblast-seeded PU scaffolds contracted significantly less and demonstrated fewer αSMA(+) myofibroblasts compared to fibroblast-seeded collagen lattices. In a murine HSc model, collagen coated PU (ccPU) scaffolds significantly reduced HSc contraction as compared to untreated control wounds and wounds treated with the clinical standard of care. Our data suggest that electrospun ccPU scaffolds meet the requirements to reduce HSc contraction including reduction of in vitro HSc related outcomes, diminished scar stiffness, and reduced scar contraction. While clinical dogma suggests treating severe burn patients with rapidly biodegrading skin equivalents, our data suggest that a more long-term scaffold may possess merit in reducing HSc. STATEMENT OF SIGNIFICANCE: In severe burns treated with skin grafting, between 30% and 90% of patients develop hypertrophic scars (HSc). There are no therapies to prevent HSc, and treatments are marginally effective. This work is the first example we are aware of which studies the impact of a permanent electrospun elastomer on HSc contraction in a murine model that mimics the human condition. Collagen coated polyurethane scaffolds decrease αSMA+ myofibroblast formation in vitro, prevent stiffening of scar tissue, and mitigate HSc contraction. Unlike current standards of care, electrospun, polyurethane scaffolds do not lose architecture over time. We propose that the future bioengineering strategy of mitigating HSc contraction should consider a long-term elastomeric matrix which persists within the wound bed throughout the remodeling phase of repair.

MicroRNAs in skin tissue engineering.

35.2 million annual cases in the U.S. require clinical intervention for major skin loss. To meet this demand, the field of skin tissue engineering has grown rapidly over the past 40 years. Traditionally, skin tissue engineering relies on the "cell-scaffold-signal" approach, whereby isolated cells are formulated into a three-dimensional substrate matrix, or scaffold, and exposed to the proper molecular, physical, and/or electrical signals to encourage growth and differentiation. However, clinically available bioengineered skin equivalents (BSEs) suffer from a number of drawbacks, including time required to generate autologous BSEs, poor allogeneic BSE survival, and physical limitations such as mass transfer issues. Additionally, different types of skin wounds require different BSE designs. MicroRNA has recently emerged as a new and exciting field of RNA interference that can overcome the barriers of BSE design. MicroRNA can regulate cellular behavior, change the bioactive milieu of the skin, and be delivered to skin tissue in a number of ways. While it is still in its infancy, the use of microRNAs in skin tissue engineering offers the opportunity to both enhance and expand a field for which there is still a vast unmet clinical need. Here we give a review of skin tissue engineering, focusing on the important cellular processes, bioactive mediators, and scaffolds. We further discuss potential microRNA targets for each individual component, and we conclude with possible future applications.

Mitigation of hypertrophic scar contraction via an elastomeric biodegradable scaffold.

Hypertrophic scar (HSc) occurs in 40-70% of patients treated for third degree burn injuries. Current burn therapies rely upon the use of bioengineered skin equivalents (BSEs), which assist in wound healing but do not prevent HSc contraction. HSc contraction leads to formation of a fixed, inelastic skin deformity. We propose that BSEs should maintain their architecture in the wound bed throughout the remodeling phase of repair to prevent HSc contraction. In this work we study a degradable, elastomeric, randomly oriented, electrospun micro-fibrous scaffold fabricated from the copolymer poly(l-lactide-co-ε-caprolactone) (PLCL). PLCL scaffolds displayed appropriate elastomeric and tensile characteristics for implantation beneath a human skin graft. In vitro analysis using human dermal fibroblasts demonstrated that PLCL scaffolds decreased myofibroblast formation as compared to an in vitro HSc contraction model. Using a validated immune-competent murine HSc contraction model, we found that HSc contraction was significantly greater in animals treated with standard of care, Integra, as compared to those treated with collagen coated-PLCL (ccPLCL) scaffolds. Finally, wounds treated with ccPLCL were significantly less stiff than control wounds at d30 in vivo. Together, these data suggest that scaffolds which persist throughout the remodeling phase of repair may represent a clinically translatable method to prevent HSc contraction.

A novel immune competent murine hypertrophic scar contracture model: a tool to elucidate disease mechanism and develop new therapies.

Hypertrophic scar (HSc) contraction following burn injury causes contractures. Contractures are painful and disfiguring. Current therapies are marginally effective. To study pathogenesis and develop new therapies, a murine model is needed. We have created a validated immune-competent murine HSc model. A third-degree burn was created on dorsum of C57BL/6 mice. Three days postburn, tissue was excised and grafted with ear skin. Graft contraction was analyzed and tissue harvested on different time points. Outcomes were compared with human condition to validate the model. To confirm graft survival, green fluorescent protein (GFP) mice were used, and histologic analysis was performed to differentiate between ear and back skin. Role of panniculus carnosus in contraction was analyzed. Cellularity was assessed with 4',6-diamidino-2-phenylindole. Collagen maturation was assessed with Picro-sirius red. Mast cells were stained with Toluidine blue. Macrophages were detected with F4/80 immune. Vascularity was assessed with CD31 immune. RNA for contractile proteins was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Elastic moduli of skin and scar tissue were analyzed using a microstrain analyzer. Grafts contracted to ∼45% of their original size by day 14 and maintained their size. Grafting of GFP mouse skin onto wild-type mice, and analysis of dermal thickness and hair follicle density, confirmed graft survival. Interestingly, hair follicles disappeared after grafting and regenerated in ear skin configuration by day 30. Radiological analysis revealed that panniculus carnosus doesn't contribute to contraction. Microscopic analyses showed that grafts show increase in cellularity. Granulation tissue formed after day 3. Collagen analysis revealed increases in collagen maturation over time. CD31 stain revealed increased vascularity. Macrophages and mast cells were increased. qRT-PCR showed up-regulation of transforming growth factor beta, alpha smooth muscle actin, and rho-associated protein kinase 2 in HSc. Tensile testing revealed that human skin and scar tissues are tougher than mouse skin and scar tissues.