Effects of Low-Level Laser Therapy and Purified Natural Latex (Hevea brasiliensis) Protein on Injured Sciatic Nerve in Rodents: Morpho-Functional Analysis.

The present study analyzed the effects of low-level laser therapy (LLLT) and the purified natural latex protein (Hevea brasiliensis, F1 protein) on the morpho-function of sciatic nerve crush injuries in rats. One-hundred and eight male Wistar rats were randomly allocated to six groups (n = 18): 1. Control; 2. Exposed (nerve exposed); 3. Injury (injured nerve without treatment); 4. LLLT (injured nerve irradiated with LLLT (15 J/cm2, 780 nm)); 5. F1 (injured nerve treated with F1 protein (0.1%)); and 6. LLLT + F1 (injured nerve treated with LLLT and F1). On the 1st, 7th, 14th, and 56th days after injury, a functional sensory analysis of mechanical allodynia and mechanical hyperalgesia and a motor analysis of grip strength and gait were performed. After 3, 15, and 57 days, the animals were euthanized for morphometric/ultrastructural analyses. The treatments applied revealed improvements in morphometric/ultrastructural parameters compared to the injured group. Sensory analyses suggested that the improvements observed were associated with time progression and not influenced by the treatments. Motor analyses revealed significant improvements in grip strength from the 7th day in the LLLT group and in gait from the 56th day in all treated groups. We concluded that even though the morphological analyses showed improvements with the treatments, they did not influence sensory recovery, and LLLT improved motor recovery.

Brainstem Modulates Parkinsonism-Induced Orofacial Sensorimotor Dysfunctions.

Parkinson's Disease (PD), treated with the dopamine precursor l-3,4-dihydroxyphenylalanine (L-DOPA), displays motor and non-motor orofacial manifestations. We investigated the pathophysiologic mechanisms of the lateral pterygoid muscles (LPMs) and the trigeminal system related to PD-induced orofacial manifestations. A PD rat model was produced by unilateral injection of 6-hydroxydopamine into the medial forebrain bundle. Abnormal involuntary movements (dyskinesia) and nociceptive responses were determined. We analyzed the immunodetection of Fos-B and microglia/astrocytes in trigeminal and facial nuclei and morphological markers in the LPMs. Hyperalgesia response was increased in hemiparkinsonian and dyskinetic rats. Hemiparkinsonism increased slow skeletal myosin fibers in the LPMs, while in the dyskinetic ones, these fibers decreased in the contralateral side of the lesion. Bilateral increased glycolytic metabolism and an inflammatory muscle profile were detected in dyskinetic rats. There was increased Fos-B expression in the spinal nucleus of lesioned rats and in the motor and facial nucleus in L-DOPA-induced dyskinetic rats in the contralateral side of the lesion. Glial cells were increased in the facial nucleus on the contralateral side of the lesion. Overall, spinal trigeminal nucleus activation may be associated with orofacial sensorial impairment in Parkinsonian rats, while a fatigue profile on LPMs is suggested in L-DOPA-induced dyskinesia when the motor and facial nucleus are activated.

Transcutaneous Electrical Nerve Stimulation in Nerve Regeneration: A Systematic Review of In Vivo Animal Model Studies.

OBJECTIVE: Transcutaneous electrical nerve stimulation (TENS) is a noninvasive electrical stimulation therapy indicated for pain control that has been applied for the regeneration of nerves. This systematic review aimed to analyze the evidence on TENS effectiveness on nerve regeneration. MATERIALS AND METHODS: A systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria: PubMed/MEDLINE, Web of Science, ScienceDirect, and SciELO data bases. Primary research that evaluated TENS on nerve regeneration was considered. RESULTS: Several studies have investigated the use of TENS for pain treatment. A total of six animal studies analyzed TENS for nerve regeneration. The selected articles showed high quality (Animal Research: Reporting of In Vivo Experiments guidelines), with many unclear points related to bias opportunities (Systematic Review Center for Laboratory Animal Experimentation Risk of Bias tool). In general, TENS accelerated functional and motor recovery and increased axon quantity and diameter. More specifically, the application of low-frequency TENS resulted in a continuous basal lamina; a higher density of fibers with normal diameters, indicating normal myelination, showed signs of deterioration and delayed nerve regeneration. In contrast, the high-frequency TENS application stimulated motor regeneration and increased the diameter of the regenerated axons but revealed a small number of axons, demyelination, dark axoplasm, and an increase in the predisposition of neuropathic pain. CONCLUSIONS: Although there is some heterogeneous evidence in animal research, TENS seems to be a promising treatment for nerve injury that should be better explored. It is still necessary to improve the analysis of its application parameters, which can lead to the most satisfactory regeneration results and improve the understanding of its mechanisms on peripheral nerve regeneration.

Analysis of the Chemical Composition and Morphological Characterization of Tissue Osseointegrated to a Dental Implant after 5 Years of Function.

Osseointegration implies the coexistence of a biocompatible implant subjected to masticatory loads and living bone tissue adhered to its surface; this interaction is a critical process for the success of implants. The objective of this work is to analyze the osseoformation and osseointegration of a dental implant in operation for 5 years microscopically through morphological analysis of the surface and chemical composition through a variable pressure scanning electron microscope (VP-SEM) and energy dispersive X-ray spectrometry (EDX). The chemical composition and general characteristics of the structural morphology of random areas of the surfaces of an osseointegrated dental implant from an ex vivo sample were analyzed. On the surface of the implant free of bone tissue, titanium (TI) was mainly identified in the area of the implant threads and carbon (C) in the depth of the implant threads. Phosphorus (P), calcium (Ca), oxygen (O), carbon (C), with dense and homogeneous distribution, and, to a lesser extent, sodium (Na) were detected on the bone surface around the contour of the implant. Regarding the morphological characteristics of the implant surface, a rough structure with some irregularities and detachments of the implant lodged in the bone tissue was observed. Microscopic analysis showed calcified bone tissue distributed in an orderly manner on the coronal and medial surface and sinuous and irregular in the apical area, with the presence of red blood cells. The composition of the implant allows a dynamic process of bone remodeling and regeneration subject to the biological and mechanical needs of the operation. Dental implants are shown to have exceptional and long-lasting biocompatibility that enables the formation of mature peri-implant bone tissue.

Clinical evaluation of single 4-mm implants in the posterior mandible: A 3-year follow-up pilot study.

STATEMENT OF PROBLEM: Extra-short implants in the posterior mandible can increase the functional surface area and reduce the risk of implant overload. However, reports of treatment using single extra-short implants in the posterior mandible with a midterm follow-up are lacking. PURPOSE: The purpose of this prospective pilot study was to evaluate the clinical behavior of single extra-short 4-mm implants placed in the posterior mandible during a follow-up of 3 years from implant restoration. MATERIAL AND METHODS: A total of 18 participants with a single extra-short 4-mm-long implant placed in the area of the mandibular first molars participated in this pilot study. The survival and success rates of implants, as well as biologic and prosthetic variables, were evaluated during a follow-up of 3 years from implant restoration. RESULTS: The survival rate of the implants was 100%, with no implant or biologic complications recorded. One prosthetic complication (loosening of 1 screw) was observed. CONCLUSIONS: Single extra-short (4 mm) implants in the posterior mandible showed favorable clinical behavior during the first 3-years of follow-up.

Mandibular border movements: The two envelopes of motion.

BACKGROUND: The envelope of motion is a diagrammatic representation of the mandibular border movements. Classically, those movements are carried out eccentrically; starting from the position of maximal intercuspation, the mandible describes an excursion movement until reaching maximal mouth opening. Reverse movements would describe a different path, but up to now concentric development of mandibular border movements has not been considered. Literature states that beyond mandibular border movements limits, no movement is possible. Therefore, it is of great interest to compare both paths-both envelopes of motion-and define the actual limits of mandibular movement. OBJECTIVE: The aim of this study was to compare the geometric characteristics of mandibular border movements carried out eccentrically and concentrically by healthy subjects. METHODS: Sixteen individuals aged between 18 and 27 years, molar class I and with no temporomandibular disorders, participated in the study. Eccentric and concentric mandibular movements were recorded using a 3D electromagnetic articulograph. Data were processed with computational scripts developed in MATLAB. Maximum mouth opening, trajectories, displacement ranges, polygon areas and chewing cycle area/ mandibular border movements area ratio were analysed. RESULTS: The frontal plane showed significant differences in all the parameters evaluated. Higher values were registered in the concentric area of the border movement envelope (P = .008) and in the trajectories on both sides. Statistical differences were observed in polygon areas (P = .006) in the sagittal plane and right ranges (P = .046) in the horizontal plane. CONCLUSION: Concentric mandibular movements revealed significant differences in three-dimensional trajectories in the frontal plane.

Symmetry of mandibular movements: A 3D electromagnetic articulography technique applied on asymptomatic participants.

STATEMENT OF PROBLEM: Asymmetries in mandibular movements (MMs) can be found in patients with some temporomandibular joint disorders, condylar fracture, or after orthognathic or orthodontic surgery. Quality and symmetry of the MMs should be recorded and analyzed. However, methods for this purpose are limited. PURPOSE: The purpose of this clinical study was to determine the symmetry of MMs on asymptomatic participants by applying an innovative technique based on 3D electromagnetic articulography. MATERIAL AND METHODS: The symmetry of MMs was studied in 16 fully dentate participants (8 men and 8 women). A 3D electromagnetic articulograph was used to register MM by placing a sensor on the interincisal midline of the mandible. The border movements related to the frontal (FP), sagittal (SP), and horizontal (HP) polygons of the Posselt envelope of motion were recorded, as well as masticatory movements. Digital data processing was applied to calculate the trajectory and ranges of mandible displacement, area of the right and left sectors of FP and HP, similarity index between the right and left sectors of FP and HP, and orientation of the individualized masticatory cycles. The Shapiro-Wilk statistical test was used to determine the normality of the sample. To compare the characteristics of the right and left sectors of the polygons, a paired-samples t test (normal distributions) and Wilcoxon test for paired samples (non-normal distributions) were applied (α=.05). RESULTS: No statistically significant differences were found between the right and left sectors of the frontal and horizontal polygons in terms of trajectory (FP, P=.408; HP, P=.417), ranges of movement (FP, P=.736; HP, P=.650), areas (FP, P=.736; HP, P=.233), or orientation of the cycles (P=.506). The similarity index between the morphology of the right and left sectors of the polygons was 68 ±12% for the FP and 67 ±11% for the HP. The areas, trajectories, and ranges had similar values, but they had a different morphology on each side of the polygons. Regarding masticatory cycles, a balanced distribution was observed in terms of their orientation. CONCLUSIONS: The technique used allowed the assessment of symmetry of MM on asymptomatic participants. The evaluated parameters maintain similar values at both left and right sides; however, a different morphology of the trajectories and areas was observed.

A Novel Three-Dimensional Analysis of Tongue Movement During Water and Saliva Deglutition: A Preliminary Study on Swallowing Patterns.

Deglutition is a complex oral function, and the study of the whole process requires a precise analysis of the elements involved, especially of the tongue biomechanics. We described a three-dimensional analysis of tongue movements during both saliva and water deglutition in participants with normal occlusion. Fourteen participants (25.36 ± 4.85 years) were evaluated, and the movements of anterior, middle, and posterior portions of the tongue were recorded using AG501 3D-electromagnetic articulograph. An average volume (AVS) for water deglutition was determined for each participant. Saliva deglutition was classified according to Bourdiol et al. 35.71% was type I, 14.29% type II, and 50% type III. The greatest displacement on the inferior-superior axis was in the posterior portion, followed by the middle and anterior portions. In the posterior-anterior axis, smallest movement was in the anterior portion. During water deglutition, on the inferior-superior axis, there were statistical differences for 1-AVS between the anterior/middle and anterior/posterior portions of the tongue. There were statistical differences for both ½-AVS and »-AVS between the anterior/posterior portions of the tongue. On the posterior-anterior axis, there were no statistical differences among any volume-portion relations. On the medial-lateral axis, there was statistical difference for the ½-AVS between middle and posterior portions. The movement of the tongue portions was influenced by the volume and the element to be swallowed. The amplitude of the movement was directly proportional to the volume of water swallowed.

Analysis of the variation in low-level laser energy density on the crushed sciatic nerves of rats: a morphological, quantitative, and morphometric study.

The objective of this study was to evaluate three energy densities of low-level laser therapy (LLLT, GaAlAs, 780 nm, 40 mW, 0.04 cm2) for the treatment of lesions to peripheral nerves using the sciatic nerve of rats injured via crushing model (15 kgf, 5.2 MPa). Thirty Wistar rats (♂, 200-250 g) were divided into five groups (n = 6): C-control, not injured, and irradiated; L0-injured nerve without irradiation; L4-injured nerve irradiated with LLLT 4 J/cm2 (0.16 J); L10-injured nerve irradiated with LLLT 10 J/cm2 (0.4 J); and L50-injured nerve irradiated with LLLT 50 J/cm2 (2 J). The animals were sacrificed 2 weeks after the injury via perfusion with glutaraldehyde (2.5%, 0.1 M sodium cacodylate buffer). The nerve tissue was embedded in historesin, cut (3 µm), mounted on slides, and stained (Sudan black and neutral red). The morphological and quantitative analysis (myelin and blood capillary densities) and morphometric parameters (maximum and minimum diameters of nerve fibers, axon diameter, G-ratio, myelin sheath thickness) were assessed using the ImageJ software. ANOVA (parametric) or Kruskal-Wallis (nonparametric) tests were used for the statistical analysis. Groups L0, L4, L10, and L50 exhibited diminished values of all the quantitative and morphometric parameters in comparison to the control group. The morphological, quantitative, and morphometric data revealed improvement after injury in groups L4, L10, and L50 (irradiated groups) compared to the injured-only group (L0); the best results, in general, were observed for the L10 group after 15 days of nerve injury.

Properties of the tibialis anterior muscle after treatment with laser therapy and natural latex protein following sciatic nerve crush.

INTRODUCTION: In this study we evaluated the characteristics of the tibialis anterior muscle after sciatic nerve crush and treatment with low-level laser therapy (LLLT) or the protein from natural latex (P1). METHODS: We studied the following 6 groups of male Wistar rats: control (CG); exposed nerve (EG); injured nerve (IG); injured nerve with LLLT (LG); injured nerve with P1 (PG); and injured nerve with P1 and LLLT (LPG). RESULTS: After 4 weeks, muscle morphology showed improvement in the treated groups; after 8 weeks, the treated groups resembled controls, especially the PG. Morphometry revealed muscle fiber atrophy after nerve injury, with time-dependent recovery. Histochemical analysis revealed increased intermediate fiber area. The PG was more similar to controls with NADH staining, whereas the LPG more closely resembled controls with SDH staining. CONCLUSION: Treatment using only P1 proved most efficient, revealing a negative interaction between P1 and LLLT.

Morphological and morphometric analyses of crushed sciatic nerves after application of a purified protein from natural latex and hyaluronic acid hydrogel.

Hyaluronic acid hydrogels (HAHs) have been used as a carrier of substances and factors in the repair of nervous tissue. Natural latex protein (Hevea brasiliensis, F1) has shown positive effects in treating various types of tissues, including peripheral nerves. This study evaluated the F1 associated with a HAH in a controlled crush injury (axonotmesis) of the sciatic nerve in Wistar rats. The samples were photomicrographed for morphometric and quantitative analyzes using ImageJ 1.47k software (NIH, Bethesda, MD). Morphological, quantitative (myelin area/nerve area ratio and capillary density) and morphometric (minimum nerve fiber diameter, G-Ratio) data revealed an improvement in the recovery of the sciatic nerve with the application of HAH and the combination of HAH and F1 after 4 and 8 weeks of nerve injury. The most efficacious results were observed with the combination of both substances, F1 and HAH, revealing the regenerative capacity of this new biomaterial, which was hardly tested on nerve tissue.

Comprehensive Development of a Cellulose Acetate and Soy Protein-Based Scaffold for Nerve Regeneration.

BACKGROUND: The elaboration of biocompatible nerve guide conduits (NGCs) has been studied in recent years as a treatment for total nerve rupture lesions (axonotmesis). Different natural polymers have been used in these studies, including cellulose associated with soy protein. The purpose of this report was to describe manufacturing NGCs suitable for nerve regeneration using the method of dip coating and evaporation of solvent with cellulose acetate (CA) functionalized with soy protein acid hydrolysate (SPAH). METHODS: The manufacturing method and bacterial control precautions for the CA/SPAH NGCs were described. The structure of the NGCs was analyzed under a scanning electron microscope (SEM); porosity was analyzed with a degassing method using a porosimeter. Schwann cell (SCL 4.1/F7) biocompatibility of cell-seeded nerve guide conduits was evaluated with the MTT assay. RESULTS: The method employed allowed an easy elaboration and customization of NGCs, free of bacteria, with pores in the internal surface, and the uniform wall thickness allowed manipulation, which showed flexibility; additionally, the sample was suturable. The NGCs showed initial biocompatibility with Schwann cells, revealing cells adhered to the NGC structure after 5 days. CONCLUSIONS: The fabricated CA/SPAH NGCs showed adequate features to be used for peripheral nerve regeneration studies. Future reports are necessary to discuss the ideal concentration of CA and SPAH and the mechanical and physicochemical properties of this biomaterial.

Zymographic and ultrastructural evaluations after low-level laser irradiation on masseter muscle of HRS/J strain mice.

Low-level laser therapy (LLLT) has been widely used in the treatment of the stomatognathic system dysfunction; however, its biological effect remains poorly understood. This study evaluated the effect of LLLT (GaAlAs, 780 nm, 20 J/cm(2), 40 mW) on masseter muscle of HRS/J mice after different numbers of laser irradiations (three, six, and ten) for 20 s in alternate days. Three experimental groups were defined according to the number of laser irradiations and three control groups (n=5) were used. On the third day after the last irradiation, all animals were killed and the masseter muscle was removed and processed for the following analysis: (a) transmission electron microscopy, (b) zymography, (c) immunohistochemistry for vascular endothelial growth factor (VEGF) and VEGFR-2. The results showed: (a) with six laser applications, a dilation of T tubules, and sarcoplasmic reticulum cistern, increased pinocytosed vesicles in the endothelium; with ten laser applications, few pinocytic vesicles in the endothelium and condensed mitochondria. (b) Under the conditions of this study, the synthesis of other matrix metalloproteinases was not observed, only the MMP-2 and -9. (c) After ten laser irradiations, immunostaining was observed only for VEGFR-2. We conclude that after six laser applications, ultrastructural changes may facilitate the Ca(+2) transfer to cytosol and increase the fluid transport from one surface to another. The ultrastructural changes and no immunostaining for VEGF with ten applications may decrease the metabolic activity as well as damage the angiogenic process, suggesting that an effective number of laser applications may be less than ten, associating to this therapy a better cost-benefit.

Exploring Schwann Cell Behavior on Electrospun Polyhydroxybutyrate Scaffolds with Varied Pore Sizes and Fiber Thicknesses: Implications for Neural Tissue Engineering.

The placement of a polymeric electrospun scaffold is among the most promising strategies to improve nerve regeneration after critical neurotmesis. It is of great interest to investigate the effect of these structures on Schwann cells (SCs), as these cells lead nerve regeneration and functional recovery. The aim of this study was to assess SC viability and morphology when cultured on polyhydroxybutyrate (PHB) electrospun scaffolds with varied microfiber thicknesses and pore sizes. Six electrospun scaffolds were obtained using different PHB solutions and electrospinning parameters. All the scaffolds were morphologically characterized in terms of fiber thickness, pore size, and overall appearance by analyzing their SEM images. SCs seeded onto the scaffolds were analyzed in terms of viability and morphology throughout the culture period through MTT assay and SEM imaging. The SCs were cultured on three scaffolds with homogeneous smooth fibers (fiber thicknesses: 2.4 µm, 3.1 µm, and 4.3 µm; pore sizes: 16.7 µm, 22.4 µm, and 27.8 µm). SC infiltration and adhesion resulted in the formation of a three-dimensional network composed of intertwined fibers and cells. The SCs attached to the scaffolds maintained their characteristic shape and size throughout the culture period. Bigger pores and thicker fibers resulted in higher SC viability.

Effects of the combination of low-level laser irradiation and recombinant human bone morphogenetic protein-2 in bone repair.

Low-level laser irradiation (LLLI) and recombinant human bone morphogenetic protein type 2 (rhBMP-2) have been used to stimulate bone formation. LLLI stimulates proliferation of osteoblast precursor cells and cell differentiation and rhBMP-2 recruits osteoprogenitor cells to the bone healing area. This in vivo study evaluated the effects of LLLI and rhBMP-2 on the bone healing process in rats. Critical bone defects were created in the parietal bone in 42 animals, and the animals were divided into six treatment groups: (1) laser, (2) 7 µg of rhBMP-2, (3) laser and 7 µg of rhBMP-2, (4) 7 µg of rhBMP-2/monoolein gel, (5) laser and 7 µg rhBMP-2/monoolein gel, and (6) critical bone defect controls. A gallium-aluminum-arsenide diode laser was used (wavelength 780 nm, output power 60 mW, beam area 0.04 cm(2), irradiation time 80 s, energy density 120 J/cm(2), irradiance 1.5 W/cm(2)). After 15 days, the calvarial tissues were removed for histomorphometric analysis. Group 3 defects showed higher amounts of newly formed bone (37.89%) than the defects of all the other groups (P < 0.05). The amounts of new bone in defects of groups 1 and 4 were not significantly different from each other (24.00% and 24.75%, respectively), but were significantly different from the amounts in the other groups (P < 0.05). The amounts of new bone in the defects of groups 2 and 5 were not significantly different from each other (31.42% and 31.96%, respectively), but were significantly different from the amounts in the other groups (P < 0.05). Group 6 defects had 14.10% new bone formation, and this was significantly different from the amounts in the other groups (P < 0.05). It can be concluded that LLLI administered during surgery effectively accelerated healing of critical bone defects filled with pure rhBMP-2, achieving a better result than LLLI alone or the use of rhBMP-2 alone.

Carrier systems for bone morphogenetic proteins: An overview of biomaterials used for dentoalveolar and maxillofacial bone regeneration.

Different types of biomaterials have been used to fabricate carriers to deliver bone morphogenetic proteins (BMPs) in both dentoalveolar and maxillofacial bone regeneration procedures. Despite that absorbable collagen sponge (ACS) is considered the gold standard for BMP delivery, there is still some concerns regarding its use mainly due to its poor mechanical properties. To overcome this, novel systems are being developed, however, due to the wide variety of biomaterial combination, the heterogeneous assessment of newly formed tissue, and the intended clinical applications, there is still no consensus regarding which is more efficient in a particular clinical scenario. The combination of two or more biomaterials in different topological configurations has allowed specific controlled-release patterns for BMPs, improving their biological and mechanical properties compared with classical single-material carriers. However, more basic research is needed. Since the BMPs can be used in multiple clinical scenarios having different biological and mechanical needs, novel carriers should be developed in a context-specific manner. Thus, the purpose of this review is to gather current knowledge about biomaterials used to fabricate delivery systems for BMPs in both dentoalveolar and maxillofacial contexts. Aspects related with the biological, physical and mechanical characteristics of each biomaterial are also presented and discussed.

How Fiber Surface Topography Affects Interactions between Cells and Electrospun Scaffolds: A Systematic Review.

Electrospun scaffolds have a 3D fibrous structure that attempts to imitate the extracellular matrix in order to be able to host cells. It has been reported in the literature that controlling fiber surface topography produces varying results regarding cell-scaffold interactions. This review analyzes the relevant literature concerning in vitro studies to provide a better understanding of the effect that controlling fiber surface topography has on cell-scaffold interactions. A systematic approach following PRISMA, GRADE, PICO, and other standard methodological frameworks for systematic reviews was used. Different topographic interventions and their effects on cell-scaffold interactions were analyzed. Results indicate that nanopores and roughness on fiber surfaces seem to improve proliferation and adhesion of cells. The quality of the evidence is different for each studied cell-scaffold interaction, and for each studied morphological attribute. The evidence points to improvements in cell-scaffold interactions on most morphologically complex fiber surfaces. The discussion includes an in-depth evaluation of the indirectness of the evidence, as well as the potentially involved publication bias. Insights and suggestions about dose-dependency relationship, as well as the effect on particular cell and polymer types, are presented. It is concluded that topographical alterations to the fiber surface should be further studied, since results so far are promising.

Optimal Morphometric Characteristics of a Tubular Polymeric Scaffold to Promote Peripheral Nerve Regeneration: A Scoping Review.

Cellular behavior in nerve regeneration is affected by the architecture of the polymeric nerve guide conduits (NGCs); therefore, design features of polymeric NGCs are critical for neural tissue engineering. Hence, the purpose of this scoping review is to summarize the adequate quantitative/morphometric parameters of the characteristics of NGC that provide a supportive environment for nerve regeneration, enhancing the understanding of a previous study. 394 studies were found, of which 29 studies were selected. The selected studies revealed four morphometric characteristics for promoting nerve regeneration: wall thickness, fiber size, pore size, and porosity. An NGC with a wall thickness between 250-400 µm and porosity of 60-80%, with a small pore on the inner surface and a large pore on the outer surface, significantly favored nerve regeneration; resulting in an increase in nutrient permeability, retention of neurotrophic factors, and optimal mechanical properties. On the other hand, the superiority of electrospun fibers is described; however, the size of the fiber is controversial in the literature, obtaining optimal results in the range of 300 nm to 30 µm. The incorporation of these optimal morphometric characteristics will encourage nerve regeneration and help reduce the number of experimental studies as it will provide the initial morphometric parameters for the preparation of an NGC.

Methods to Characterize Electrospun Scaffold Morphology: A Critical Review.

Electrospun scaffolds can imitate the hierarchical structures present in the extracellular matrix, representing one of the main concerns of modern tissue engineering. They are characterized in order to evaluate their capability to support cells or to provide guidelines for reproducibility. The issues with widely used methods for morphological characterization are discussed in order to provide insight into a desirable methodology for electrospun scaffold characterization. Reported methods include imaging and physical measurements. Characterization methods harbor inherent limitations and benefits, and these are discussed and presented in a comprehensive selection matrix to provide researchers with the adequate tools and insights required to characterize their electrospun scaffolds. It is shown that imaging methods present the most benefits, with drawbacks being limited to required costs and expertise. By making use of more appropriate characterization, researchers will avoid measurements that do not represent their scaffolds and perhaps might discover that they can extract more characteristics from their scaffold at no further cost.

Polyhydroxybutyrate (PHB) Scaffolds for Peripheral Nerve Regeneration: A Systematic Review of Animal Models.

In the last two decades, artificial scaffolds for nerve regeneration have been produced using a variety of polymers. Polyhydroxybutyrate (PHB) is a natural polyester that can be easily processed and offer several advantages; hence, the purpose of this review is to provide a better understanding of the efficacy of therapeutic approaches involving PHB scaffolds in promoting peripheral nerve regeneration following nerve dissection in animal models. A systematic literature review was performed following the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) criteria. The revised databases were: Pub-Med/MEDLINE, Web of Science, Science Direct, EMBASE, and SCOPUS. Sixteen studies were included in this review. Different animal models and nerves were studied. Extension of nerve gaps reconnected by PHB scaffolds and the time periods of analysis were varied. The additives included in the scaffolds, if any, were growth factors, neurotrophins, other biopolymers, and neural progenitor cells. The analysis of the quality of the studies revealed good quality in general, with some aspects that could be improved. The analysis of the risk of bias revealed several weaknesses in all studies. The use of PHB as a biomaterial to prepare tubular scaffolds for nerve regeneration was shown to be promising. The incorporation of additives appears to be a trend that improves nerve regeneration. One of the main weaknesses of the reviewed articles was the lack of standardized experimentation on animals. It is recommended to follow the currently available guidelines to improve the design, avoid the risk of bias, maximize the quality of studies, and enhance translationality.