Chitosan-Based Biomaterials for Tissue Regeneration.

Chitosan is a chitin-derived biopolymer that has shown great potential for tissue regeneration and controlled drug delivery. It has numerous qualities that make it attractive for biomedical applications such as biocompatibility, low toxicity, broad-spectrum antimicrobial activity, and many others. Importantly, chitosan can be fabricated into a variety of structures including nanoparticles, scaffolds, hydrogels, and membranes, which can be tailored to deliver a desirable outcome. Composite chitosan-based biomaterials have been demonstrated to stimulate in vivo regeneration and the repair of various tissues and organs, including but not limited to, bone, cartilage, dental, skin, nerve, cardiac, and other tissues. Specifically, de novo tissue formation, resident stem cell differentiation, and extracellular matrix reconstruction were observed in multiple preclinical models of different tissue injuries upon treatment with chitosan-based formulations. Moreover, chitosan structures have been proven to be efficient carriers for medications, genes, and bioactive compounds since they can maintain the sustained release of these therapeutics. In this review, we discuss the most recently published applications of chitosan-based biomaterials for different tissue and organ regeneration as well as the delivery of various therapeutics.

Mimicking Extracellular Matrix via Engineered Nanostructured Biomaterials for Neural Repair.

Extracellular matrix (ECM) consists of proteins, proteoglycans, and different soluble molecules. ECM provides structural support to mammalian cells. ECM is responsible for important cell functions, as well as assembling cells into various tissues and organs, regulating growth and cell-cell interaction. Recent studies have shown the potential of nanostructured biomaterials to mimic native ECM. Developing tailor-made biomaterials that mimic the complex nanoscale mesh of local ECM is not a trivial endeavor: bio-inspired biomaterials are designed to supply a healthy ECMlike structure, capable of filling the lesion cavity, favoring transplanted cell engraftment, providing physical support to endogenous neurogenesis and also tuning the inflammatory response to protect spared neurons. The strategies used to manufacture biomimetic hydrogel scaffold represent particularly important prospects of novel therapies for CNS regeneration. During this review, we describe with details the most promising regulatory pathways from ECM involved in the CNS injury and regeneration and we draw a line to the biomimetic potential of engineered nanostructured biomaterials aimed at mimicking extracellular matrix constructs and favoring the release of pro-regenerative agents. Lastly, a brief overview of their application in clinical trials is provided.

Assessment of the Effects of Swimming as a Postoperative Rehabilitation on Nerve Regeneration of Wistar Rats Submitted to Grafting of Autologous Nerves after Injury to the Sciatic Nerve.

Objective To evaluate the effects of swimming on nerve regeneration after sciatic nerve injury in Wistar rats. Methods A total of 30 Wistar rats was divided into 3 groups: Sham + Nat group animals that were not submitted to graft surgery and were submitted to swimming ( n = 10); Graft group: animals submitted to autologous sciatic nerve graft ( n = 10); and Graft + Nat group: animals submitted to autologous sciatic nerve graft surgery and to swimming ( n = 10). The results were analyzed on the software (GraphPad Software, San Diego, CA, USA). Results In the first evaluation, all sciatic functional index (SFI) values were similar ( p = 0.609). Thirty days after the surgical procedure, we observed differences between all the comparisons: Sham + Nat (-34.64 ± 13.89) versus Graft (-145.9 ± 26.06); Sham + Nat versus Graft + Nat (-89.40 ± 7.501); Graft (-145.9 ± 26.06) versus Graft + Nat (-89.40 ± 7.501). In the measurements (60 and 90 days), there was no statistical difference between the Graft and Graft + Nat groups, with significantly lower values in relation to the control group ( p < 0.001). The number of motor neurons presented differences in the comparisons between the Sham + Nat and Graft groups (647.1 ± 16.42 versus 563.4 ± 8.07; p < 0.05), and between the Sham + Nat and Graft + Nat groups (647.1 ± 16.42 versus 558.8 ± 14.79; p < 0.05). There was no difference between the Graft and Graft + Nat groups. Conclusion Animals submitted to the swimming protocol after the sciatic nerve grafting procedure did not present differences in the SFI values and motor neuron numbers when compared to the control group. Therefore, this type of protocol is not efficient for the rehabilitation of peripheral nerve lesions that require grafting. Therefore, further studies are needed.

Assessment of the Effects of Swimming as a Postoperative Rehabilitation on Nerve Regeneration of Wistar Rats Submitted to Grafting of Autologous Nerves after Injury to the Sciatic Nerve / Avaliação dos efeitos da natação como reabilitação pós-operatória na regeneração nervosa de ratos da linhagem Wistar submetidos a enxerto de nervos autólogos após lesão do nervo ciático

Abstract Objective To evaluate the effects of swimming on nerve regeneration after sciatic nerve injury in Wistar rats. Methods A total of 30 Wistar rats was divided into 3 groups: Sham + Nat group animals that were not submitted to graft surgery and were submitted to swimming (n = 10); Graft group: animals submitted to autologous sciatic nerve graft (n = 10); and Graft + Nat group: animals submitted to autologous sciatic nerve graft surgery and to swimming (n = 10). The results were analyzed on the software (GraphPad Software, San Diego, CA, USA). Results In the first evaluation, all sciatic functional index (SFI) values were similar (p = 0.609). Thirty days after the surgical procedure, we observed differences between all the comparisons: Sham + Nat (−34.64 ± 13.89) versus Graft (−145.9 ± 26.06); Sham + Nat versus Graft + Nat (−89.40 ± 7.501); Graft (−145.9 ± 26.06) versus Graft + Nat (−89.40 ± 7.501). In the measurements (60 and 90 days), there was no statistical difference between the Graft and Graft + Nat groups, with significantly lower values in relation to the control group (p < 0.001). The number of motor neurons presented differences in the comparisons between the Sham + Nat and Graft groups (647.1 ± 16.42 versus 563.4 ± 8.07; p < 0.05), and between the Sham + Nat and Graft + Nat groups (647.1 ± 16.42 versus 558.8 ± 14.79; p < 0.05). There was no difference between the Graft and Graft + Nat groups. Conclusion Animals submitted to the swimming protocol after the sciatic nerve grafting procedure did not present differences in the SFI values and motor neuron numbers when compared to the control group. Therefore, this type of protocol is not efficient for the rehabilitation of peripheral nerve lesions that require grafting. Therefore, further studies are needed.

Resumo Objetivo Avaliar os efeitos da natação na regeneração nervosa após a lesão do nervo ciático em ratos Wistar. Métodos Um total de 30 ratos Wistar foram divididos em 3 grupos: grupo Sham + Nat: animais que não foram submetidos à cirurgia de enxerto e foram submetidos à natação (n = 10); grupo Enxerto: animais que foram submetidos à cirurgia de enxerto autólogo de nervo ciático (n = 10); e grupo Enx + Nat: animais submetidos à cirurgia de enxerto autólogo de nervo ciático e à natação (n = 10). Os resultados foram analisados pelo software GraphPad Prism 5.0 (GraphPad Software, San Diego, CA, EUA). Resultados Na primeira avaliação, todos os valores do índice funcional do ciático (IFC) foram semelhantes (p = 0.609). Após 30 dias do procedimento cirúrgico, foram observadas diferenças entre todas as comparações: Sham + Nat (−34,64 ± 13,89) versus Enxerto (−145,9 ± 26,06), grupos Sham + Nat versus Enx + Nat (−89,40 ± 7,501), grupos Enxerto (−145,9 ± 26,06) versus Enx + Nat (−89,40 ± 7,501). Nas medidas (60 e 90 dias), não houve diferença estatística entre os grupos Enxerto e Enx + Nat, com valores significativamente menores em relação ao grupo controle (p < 0,001). O número de motoneurônios apresentou diferenças nas comparações entre os grupos Sham + Nat e Enxerto (647,1 ± 16,42 versus 563,4 ± 8,07; p < 0,05) e Sham + Nat e Enx + Nat (647,1 ± 16,42 versus 558,8 ± 14,79; p < 0,05), não havendo diferença entre os grupos Enxerto e Enx + Nat. Conclusão Os animais submetidos ao protocolo de natação após o procedimento de enxerto do nervo ciático não apresentaram diferenças nos valores de IFC e nos números de motoneurônios quando comparados com grupo controle. Portanto, este tipo de protocolo não é eficiente para reabilitação de lesões nervosas periféricas que necessitam de enxerto, sendo necessários novos estudos.

Advances of tooth-derived stem cells in neural diseases treatments and nerve tissue regeneration.

Nerous system diseases, both central and peripheral, bring an incredible burden onto patients and enormously reduce their quality of life. Currently, there are still no effective treatments to repair nerve lesions that do not have side effects. Stem cell-based therapies, especially those using dental stem cells, bring new hope to neural diseases. Dental stem cells, derived from the neural crest, have many characteristics that are similar to neural cells, indicating that they can be an ideal source of cells for neural regeneration and repair. This review summarizes the neural traits of all the dental cell types, including DPSCs, PDLCs, DFCs, APSCs and their potential applications in nervous system diseases. We have summed up the advantages of dental stem cells in neural repair, such as their neurotrophic and neuroprotective traits, easy harvest and low rejective reaction rate, among others. Taken together, dental stem cells are an ideal cell source for neural tissue regeneration and repair.

Sensory recovery after primary repair of palmar digital nerves using a Revolnerv(®) collagen conduit: a prospective series of 27 cases.

Despite advances in microsurgery, digital nerve repair remains a challenge due to the lack of reproducible procedures with satisfactory functional results. The aim of this study was to compare the sensory and functional results of direct microsurgical sutures protected by a Revolnerv(®) nerve regeneration conduit, with results of a series of direct sutures without a protective conduit in the literature. From November 2009 to April 2010, 35 patients were treated by direct epiperineural suture for digital nerve injury, protected by a Revolnerv(®) nerve regeneration conduit at the FESUM centre "SOS-mains Lesquin/CHRU de Lille". Sensory recovery was assessed by the static two-point discrimination Weber test (WS) and the Semmes-Weinstein (SW) test at postoperative months 1, 3, and 6. The final evaluation was performed after a minimum follow-up of 6 months. Statistical analysis of sensory results (WS and SW) was mainly performed with non-parametric tests (Wilcoxon, Mann and Whitney). P<0.05 was considered to be statistically significant. One patient was excluded, six were lost to follow-up, and four could not be seen at the 6-month follow-up visit. Finally, 24 patients and 27 nerve sutures were included. Mean age was 38 years old and the ratio of women/men was 1/5. Eighty-five percent of the patients had useful (S3+) or normal (S4) discrimination at 6 months, and the average WS was 10.3 (±3.76). There was a tendency to better WS results in sharp transections compared to jagged lacerations (9.19 vs 11.82). The SW test was satisfactory in 15% of patients and acceptable in 30%. There were no complications from the Revolnerv(®) collagen tube. After 6 months follow-up this study shows that results with the Revolnerv(®) nerve regeneration conduit on direct palmar digital nerve sutures were comparable to but not better than those of uncoated direct sutures. A study including a larger population with longer follow-up is necessary to determine the value of this technique and its recommendation for general use in all digital nerve injuries.

Low level laser in odontostomatology practice, a critical review / Láser de baja potencia en la práctica odontoestomatológica, una revisión bibliográfica

The application of laser as a therapeutic measure in nervous regeneration in dentistry has not been a discussed subject, even though the knowledge about the response of the peripheral nervous system is very important inpractice as well as in the recovery of the patient. It has been proposed that low-level laser (LLL) therapy has beneficial effects on tissues; LLL therapy acts as an analgesic, anti-inflammatory, anti-edematous, anti-cellulitic tool, and it stimulates cellular trofism. In the present study, we conducted a meta-analysis of available literature regarding the response of the injured nerveto low-power laser using search engines EBSCO and PUBMED. The literature refers to the stimulant effect of the low-level laser in the neoformation of vessels and to the existing bibliographic evidence to propose that this mechanism is important in nervous regeneration. There is limited bibliographic evidence on the effects of LLL therapy in dentistry.

La aplicación de láser como medio terapéutico en la regeneración nerviosa en odontología, no ha sido un tema muy discutido, aún cuando el conocimiento de la respuesta del sistema nervioso periférico es muy importante tanto en la práctica como en la recuperación del paciente. Se ha propuesto que el láser de baja potencia (LBP) tiene efectos benéficos en los tejidos, entre ellos antiálgico, antiinflamatorio, antiedematoso, anticelulítico y bioestimulante del trofismo celular. En el presente estudio se realizó un metaanálisis de la literatura disponible en relación con la respuesta del nervio lesionado ante la aplicación de láser de baja potencia utilizando los buscadores EBSCO y PUBMED. La literatura se refiere al efecto estimulante del LBP en la neoformación de vasos y existiendo evidencia bibliográfica para proponer a este mecanismo como importante en la regeneración nerviosa. Los efectos del láser de baja potencia en Odontología presentaron una escasa evidencia bibliográfica.

Nervo alógeno conservado em glicerol: estudo experimental em ratos / Glycerol-preserved allogenous nerve: an experimental study with rats

A utilização de aloenxerto de nervo conservado em glicerol é uma alternativa a auto-enxertia em casos de lesões de nervos periféricos com perda de substância que diminui a morbidade cirúrgica e provem material suficiente para a reparação neural. O objetivo deste trabalho foi comparar o grau de reparação nervosa, utilizando análises histológica e funcional, através da interposição de enxerto autógeno (grupo A), de tubo de veia conservada em glicerol (grupo B) e de interposição de nervo alógeno conservado em glicerol (grupo C) em defeitos de 5 mm no nervo fibular de ratos Wistar. A análise histológica foi feita após o sacrifício dos animais( 6 semanas) , usando o corante azul de toluidina a 1 por cento. No grupo A (auto-enxerto) verificou-se reação tecidual perineural e escape de fibras axonais mielinizadas para fora dos limites do epineuro que foi maior se comparada ao verificado no Grupo B (Veia autógena + glicerol) e Grupo C (aloenxerto de nervo).A avaliação funcional foi feita através da análise dos padrões das pegadas das patas posteriores dos ratos ("Walking Track Analysis"), nos períodos: pré-operatório, pós-operatório imediato, na terceira e sexta semanas. Na recuperação funcional, não houve diferença estatisticamente significativa entre os três grupos em nenhum dos períodos avaliados.

The use of glycerol-preserved nerve allograft is an alternative to autografting in cases of peripheral nerve injury with loss of substance, which decreases surgical morbidity and provides sufficient material for neural repair. The objective of this study was to compare the degree of nervous repair, through interposition of autogenous graft (Group A), of glycerol-preserved vein tube (Group B), and interposition of glycerol-preserved allogenic nerve (Group C) in 5-mm defects of Wistar rats' fibular nerve, using histological and functional analyses. In group A (autograft) a perineural tissue reaction and myelinated axonal fibers escape out of the epineurium boundaries were greater when compared to those observed in Group B (autogenous vein + glycerol) and Group C (nerve allograft). The functional evaluation was made by analysis of the patterns of rats' posterior footprints (Walking Track Analysis) in preoperative, early postoperative period, week 3 and week 6. Regarding functional recovery, in none of the evaluated periods was there a statistically significant difference between the three groups.

Cellular and Molecular Biological Mechanisms of Peripheral Nerve Selective Regeneration (review) / 中国康复理论与实践

@#: The management of peripheral nerve injury is a tough problem clinically.Intensive studies in the past were focused on the bridging of nerve defects and the improvement of regeneration rate.But actually the clinical results of functional recovery after peripheral nerve lesion is mainly decided by the accurate regeneration of axons to their original target tissues and structures.Therefore,better clinical results could be obtained by a greater understanding of the cellular and molecular biology of selective nerve regeneration and the application of this theory clinically.This paper summarized recent studies on the cellular and molecular biology mechanisms of peripheral nerve selective regeneration.