Modern Approaches to Acellular Therapy in Bone and Dental Regeneration.

An approach called cell-free therapy has rapidly developed in regenerative medicine over the past decade. Understanding the molecular mechanisms and signaling pathways involved in the internal potential of tissue repair inspires the development of new strategies aimed at controlling and enhancing these processes during regeneration. The use of stem cell mobilization, or homing for regeneration based on endogenous healing mechanisms, prompted a new concept in regenerative medicine: endogenous regenerative medicine. The application of cell-free therapeutic agents leading to the recruitment/homing of endogenous stem cells has advantages in overcoming the limitations and risks associated with cell therapy. In this review, we discuss the potential of cell-free products such as the decellularized extracellular matrix, growth factors, extracellular vesicles and miRNAs in endogenous bone and dental regeneration.

Applications of decellularized materials in tissue engineering: advantages, drawbacks and current improvements, and future perspectives.

Decellularized materials (DMs) are attracting more and more attention because of their native structures, comparatively high bioactivity, low immunogenicity and good biodegradability, which are difficult to be imitated by synthetic materials. Recently, DMs have been demonstrated to possess great potential to overcome the disadvantages of autografts and have become a kind of promising material for tissue engineering. In this systematic review, we aimed to not only provide a quick access for understanding DMs, but also bring new ideas to utilize them more appropriately in tissue engineering. Firstly, the preparation of DMs was introduced. Then, the updated applications of DMs derived from different tissues and organs in tissue engineering were comprehensively summarized. In particular, their advantages, drawbacks and current improvements were emphasized. Moreover, we analyzed and proposed future perspectives.

Tissue regeneration: an overview from stem cells to micrografts.

Regenerative medicine represents a major challenge for the scientific community. The choice of the biological sources used, such as stem cells and grafts, is crucial. Stem cell therapy is mainly related to the use of mesenchymal stem cells; however, clinical trials are still needed to investigate their safety. The micrografting technique was conceived by Cicero Parker Meek in 1958. It is based on the principle that by increasing the superficial area of skin grafts and reducing the size of its particles, it is possible to cover an area larger than the original donor site. Stem cells are pluripotent cells that have the capacity to differentiate into all cell types and are self-renewing, whereas micrografts derive from a small fragment of an autologous tissue and exhibit limited differentiative potential compared with stem cells. Therefore, stem cells and micrografts cannot be considered equivalent, although in some cases they exhibit similar regenerative potential, which is the focus of this review. Last, stem cell therapies remain limited because of complex and costly processes, making them not very feasible in clinical practice, whereas obtaining micrografts is generally a one-step procedure that does not require any advanced tissue manipulation.

Repair strategies for traumatic spinal cord injury, with special emphasis on novel biomaterial-based approaches.

As a part of the central nervous system (CNS), the adult mammalian spinal cord displays only very poor ability for self-repair in response to traumatic lesions, which mostly lead to more or less severe, life-long disability. While even adult CNS neurons have a certain plastic potential, their intrinsic regenerative capacity highly varies among different neuronal populations and in the end, regeneration is almost completely inhibited due to extrinsic factors such as glial scar and cystic cavity formation, excessive and persistent inflammation, presence of various inhibitory molecules, and absence of trophic support and of a growth-supportive extracellular matrix structure. In recent years, a number of experimental animal models have been developed to overcome these obstacles. Since all those studies based on a single approach have yielded only relatively modest functional recovery, it is now consensus that different therapeutic approaches will have to be combined to synergistically overcome the multiple barriers to CNS regeneration, especially in humans. In this review, we particularly emphasize the hope raised by the development of novel, implantable biomaterials that should favor the reconstruction of the damaged nervous tissue, and ultimately allow for functional recovery of sensorimotor functions. Since human spinal cord injury pathology depends on the vertebral level and the severity of the traumatic impact, and since the timing of application of the different therapeutic approaches appears very important, we argue that every case will necessitate individual evaluation, and specific adaptation of therapeutic strategies.

Regenerative robotics.

Congenital diseases requiring reconstruction of parts of the gastrointestinal tract, skin, or bone are a challenge to alleviate especially in rapidly growing children. Novel technologies may be the answer. This article presents the state-of-art in regenerative robotic technologies, which are technologies that assist tissues and organs to regenerate using sensing and mechanotherapeutical capabilities. It addresses the challenges in the development of such technologies, among which are autonomy and fault-tolerance for long-term therapy as well as morphological conformations and compliance of such devices to adapt to gradual changes of the tissues in vivo. The potential as medical devices for delivering therapies for tissue growth and as tools for scientific exploration of regenerative mechanisms is also discussed.

Human Pluripotent Stem Cells for Spinal Cord Injury.

Spinal cord injury (SCI) as a serious public health issue and neurological insult is one of the most severe cause of long-term disability. To date, a variety of techniques have been widely developed to treat central nervous system injury. Currently, clinical treatments are limited to surgical decompression and pharmacotherapy. Because of their negative effects and inefficiency, novel therapeutic approaches are required in the management of SCI. Improvement and innovation of stem cell-based therapies have a huge potential for biological and future clinical applications. Human pluripotent stem cells (hPSCs) including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are defined by their abilities to divide asymmetrically, self-renew and ultimately differentiate into various cell lineages. There are considerable research efforts to use various types of stem cells, such as ESCs, neural stem cells (NSCs), and mesenchymal stem cells (MSCs) in the treatment of patients with SCI. Moreover, the use of patient-specific iPSCs holds great potential as an unlimited cell source for generating in vivo models of SCI. In this review, we focused on the potential of hPSCs in treating SCI.

Will Tissue-Engineering Strategies Bring New Hope for the Reconstruction of Nasal Septal Cartilage?

The nasal septal cartilage plays an important role in the growth of midface and as a vertical strut preventing the collapse of the nasal bones. The repair of nasal cartilage defects remains a major challenge in reconstructive surgery. The tissue engineering strategy in the development of tissue has opened a new perspective to generate functional tissue for transplantation. Given the poor regenerative properties of cartilage and a limited amount of autologous cartilage availability, intense interest has evoked for tissue engineering approaches for cartilage development to provide better outcomes for patients who require nasal septal reconstruction. Despite numerous attempts to substitute the shapely hyaline cartilage in the nasal cartilages, many significant challenges remained unanswered. The aim of this research was to carry out a critical review of the literature on research work carried out on the development of septal cartilage using a tissue engineering approach, concerning different cell sources, scaffolds and growth factors, as well as its clinical pathway and trials have already been carried out.

High Mobility Group Box 1: An Immune-regulatory Protein.

High mobility group box 1 (HMGB1) presents in almost all somatic cells as a component of the cell nucleus. It is necessary for transcription regulation during cell development. Recent studies indicate that extracellular HMGB1, coming from necrotic cells or activated immune cells, triggers inflammatory response whereas intracellular HMGB1 controls the balance between autophagy and apoptosis. In addition, reduced HMGB1 can effectively mediate tissue regeneration. HMGB1, therefore, is regarded as a therapeutic target for inflammatory diseases. In this review, we summarized and discussed the immunomodulatory effect of HMGB1.

From deceased to bioengineered graft: New frontiers in liver transplantation.

In the worldwide context of graft shortage, several strategies have been explored to increase the number of grafts available for liver transplantation (LT). These include the use of marginal and living donors, split livers, and the improvement of marginal donor grafts (machine perfusion). However, recent advances in the understanding of liver organogenesis, stem cells, and matrix biology provide novel insights in tissue engineering. Today, the newest technologies and discoveries open the door to the development of new methods for organ implementation such as the recellularization of natural scaffolds, liver organoids, bio-printing, and tissue or generation of chimeric organs. These approaches might potentially to generate an unlimited source of grafts (allogenic or chimeric) which will be used in the near future for LT or as a temporary bridge toward LT. This qualitative review focuses on all methods of organ implementation and highlights the newest developments in tissue engineering and regenerative medicine.

Guided growth for caput valgum in developmental dysplasia of the hip.

This study reported guided growth for caput valgum deformity and subsequent hip development. Ten children with unilateral hip dysplasia had guided growth by one eccentric transphyseal screw at age 9.1 years with minimum 2 years of follow-up. The first change was decreasing articulotrochanteric distance and then increasing physis tilt angle and head-shaft angle by 1.5 years. The center edge angle that was significantly less than the normal side (18.3 vs. 24.8°) preoperatively became comparable between both the hips 2 years later. Rebounding of physis inclination after screw back out suggested mechanical tethering, rather than permanent physis closure, resulted in morphologic changes in the femur. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Augmenting endogenous repair of soft tissues with nanofibre scaffolds.

As our ability to engineer nanoscale materials has developed we can now influence endogenous cellular processes with increasing precision. Consequently, the use of biomaterials to induce and guide the repair and regeneration of tissues is a rapidly developing area. This review focuses on soft tissue engineering, it will discuss the types of biomaterial scaffolds available before exploring physical, chemical and biological modifications to synthetic scaffolds. We will consider how these properties, in combination, can provide a precise design process, with the potential to meet the requirements of the injured and diseased soft tissue niche. Finally, we frame our discussions within clinical trial design and the regulatory framework, the consideration of which is fundamental to the successful translation of new biomaterials.

Injectable biomaterials for stem cell delivery and tissue regeneration.

INTRODUCTION: Organ dysfunction and failure are major health issues affecting millions of patients, many of whom are desperate for organ transplantation. Tissue regeneration aims at providing alternative solutions through innovative application of cell biology and materials engineering to clinical practice. Biomaterials play a critical role in tissue engineering, which interface with both cell biology and surgical procedures. Injectable stem cell carriers represent a promising platform to harvest the therapeutic effects of cells and to simplify the surgical process. Areas covered: This review is focused on injectable cell carriers which are not only expected to improve therapeutic outcomes, but also to facilitate easy surgical process. Such cell carriers include in situ gelling hydrogel, injectable supramolecular hydrogels, and microcarriers. Expert opinion: The current design of hydrogels and microcarriers can achieve biocompatibility, biodegradability, and provide desirable features to enhance biological response. Overall, more systematic understanding of stem cell behaviors in a synthetic microenvironment, as well as advancement in materials sciences, are needed to design injectable biomaterials that can provide all critical guidance for the full course of tissue regeneration.

Radioterapia de rescate en pacientes con cáncer de próstata. Planificación, respuesta al tratamiento y pronóstico mediante PET/TC con 11C-colina / Salvage radiotherapy in prostate cancer patients. Planning, treatment response and prognosis using 11C-choline PET/CT

Objetivo. Evaluar el valor pronóstico de la respuesta terapéutica mediante 11C-colina PET/TC en pacientes con recidiva bioquímica de cáncer de próstata en los que la exploración ha indicado el tratamiento con radioterapia radioguiada. Método. Treinta y siete pacientes inicialmente tratados con prostatectomía, acudieron por recidiva bioquímica. La 11C-colina PET/TC permitió la detección de infiltración adenopática infradiafragmática. Todos ellos fueron seleccionados para radioterapia de intensidad modulada, escalando la dosis según los hallazgos de la PET/TC. Al año se les realizó PSA y 11C-colina PET/TC categorizando la respuesta (completa/parcial/progresión). Se efectuó seguimiento clínico/analítico/imagen hasta aparición de segunda recidiva o 36 meses en pacientes libres de enfermedad. Resultados. La 11C-colina PET/TC permitió la detección adenopática en los 37 pacientes. En 18 (48,6%) fue supracentimétrica y en 19 (51,3%) no había criterios patológicos por TC: 9 (24,3%) ganglios positivos supra + infracentimétricos y 10 (27,0%) únicamente infracentimétricos. Categorizamos la respuesta mediante 11C-colina PET/TC un año tras la radioterapia: 16 pacientes (43,2%) respuesta completa; 15 (40,5%) respuesta parcial; 6 (16,2%) progresión. La respuesta fue concordante entre PSA y 11C-colina PET/TC en 32 pacientes (86,5%) y discordante en 5 (13,5%). Se detectó nueva recidiva en 12 pacientes (80%) con respuesta parcial y en 5 (31,2%) con respuesta completa. La media de tiempo libre de enfermedad ha sido 9 meses tras respuesta parcial y 18 meses tras respuesta completa (diferencia significativa, p < 0,0001). Conclusión. La 11C-colina PET/TC permite la selección de los pacientes con recidiva de cáncer de próstata candidatos a radioterapia, planificando la misma. La evaluación de la respuesta terapéutica mediante 11C-colina PET/TC presenta significación pronóstica (AU)

Objective. To assess the prognostic value of the therapeutic response by 11C-choline PET/CT in prostate cancer patients with biochemical recurrence in which 11C-choline PET/CT indicated radio-guided radiotherapy. Methods. The study included 37 patients initially treated with prostatectomy, who were treated due to biochemical recurrence. 11C-choline PE/CT detected infra-diaphragmatic lymph-node involvement. All were selected for intensity modulated radiation therapy, escalating the dose according to the PET findings. One year after treatment patients underwent PSA and 11C-choline PET/CT categorizing response (complete/partial/progression). Clinical/biochemical/image monitoring was performed until appearance of second relapse or 36 months in disease-free patients. Results. 11C-choline PET/CT could detect lymph nodes in all 37 patients. They were 18 (48.6%) of more than a centimetre in size and 19 (51.3%) with no pathological CT morphology: 9 (24.3%) with positive lymph nodes of around one centimetre and 10 (27.0%) only less than a centimetre in size. The response by 11C-choline PET/CT was categorised one year after radiotherapy: 16 patients (43.2%) complete response; 15 (40.5%) partial response, and 6 (16.2%) progression. The response was concordant between the PSA result and 11C-choline PET/CT in 32 patients (86.5%), and discordant in five (13.5%). New recurrence was detected in 12 patients (80%) with partial response, and 5 (31.2%) with complete response. The mean time to recurrence was 9 months after partial response, and 18 months after complete response (significant difference, p<.0001). Conclusion. 11C-choline PET/CT allows the selection of patients with recurrent prostate cancer candidates for radiotherapy and to plan the technique. The evaluation of therapeutic response by 11C-choline PET/CT has prognostic significance (AU)

[Possibilities and prospects of three-dimensional bioprinting in vascular surgery].

Rapid development of tissue engineering is gradually changing the approach to patient care. Despite the fact that the use of an autograft or transplantation of an artificial prosthesis is preferred in most cases, this is frequently impossible due to shortage of suitable material or the patient's condition. Regenerative medicine and tissue engineering make it possible to reduce the terms of treatment and restoration after vascular operations, as well as complications rate. At the present moment there is a lot of information about methods of biofabrication and multiple techniques of using stem cells. Nevertheless, clinical efficacy of these methods requires further detailed examination. The review of literature contains the data concerning modern achievements in the area of bioprinting.

Implantes dentales en pacientes adultos postrauma dentoalveolar. Estudio descriptivo / Dental implants in adults after dentoalveolar injuries. Descriptive study

Objetivo. Realizar un estudio descriptivo y retrospectivo para analizar el éxito de la rehabilitación dentaria con o sin aumento óseo alveolar. Materiales y métodos. Se realizó un estudio retrospectivo mediante la revisión de historias clínicas de pacientes que concurrieron al Servicio de Cirugía Máxilofacial del Hospital Clínico Mutual de Seguridad, Chile, en el período de 3 años (enero 2003 - diciembre 2005). Resultados. Un total de 135 pacientes ingresaron al estudio en los cuales se instalaron 246 implantes dentales. Se registraron 8 pérdidas de implantes en el seguimiento. Conclusiones. En este estudio se presenta un protocolo establecido y se establece la necesidad de un diagnóstico detallado para planificar la rehabilitación mediante implantes dentales posterior a un trauma con un equipo multidisciplinario (AU)

Objectives. Conduct a retrospective study to analyse the success of dental implant treatment with or without bone ridge augmentation. Materials and methods. A retrospective study was made by reviewing medical records of patients who attended the Maxillofacial Surgery Service of Hospital Mutual de Seguridad, Chile. In the period of three years (January 2003 - December 2005). Results. There were a total of 135 patients with 246 dental implants indications. 8 cases with dental implant loss where registered. Conclusions. This study presents a proposal protocol, and establishes the need of a detail diagnosis to design the post-traumatic implant rehabilitation treatment with a multidisciplinary team (AU)

Could a functional artificial skeletal muscle be useful in muscle wasting?

PURPOSE OF REVIEW: Regardless of the underlying cause, skeletal muscle wasting is detrimental for a person's life quality, leading to impaired strength, locomotion, and physiological activity. Here, we propose a series of studies presenting tissue engineering-based approaches to reconstruct artificial muscle in vitro and in vivo. RECENT FINDINGS: Skeletal muscle tissue engineering is attracting more and more attention from scientists, clinicians, patients, and media, thanks to the promising results obtained in the last decade with animal models of muscle wasting. The use of novel and refined biomimetic scaffolds mimicking three-dimensional muscle environment, thus supporting cell survival and differentiation, in combination with well characterized myogenic stem/progenitor cells, revealed the noteworthy potential of these technologies for creating artificial skeletal muscle tissue. In vitro, the production of three-dimensional muscle structures offer the possibility to generate a drug-screening platform for patient-specific pharmacological treatment, opening new frontiers in the development of new compounds with specific therapeutic actions. In vivo, three-dimensional artificial muscle biomimetic constructs offer the possibility to replace, in part or entirely, wasted muscle by means of straight reconstruction and/or by enhancing endogenous regeneration. SUMMARY: Reports of tissue engineering approaches for artificial muscle building appeared in large numbers in the specialized press lately, advocating the suitability of this technology for human application upon scaling up and a near future applicability for medical care of muscle wasting. VIDEO ABSTRACT: http://links.lww.com/COCN/A9

Recent therapeutic approaches for spinal cord injury.

A spinal cord injury (SCI) often causes permanent changes in strength and sensation functions below the site of the injury and affects thousands of people each year. Transplantation of stem cells is a promising approach in acute SCI as it may support spinal cord repair. However, in case of chronic SCI greater amounts of nervous tissue have to be regenerated, leaving scaffold transplantation the only feasible option for cellular engraftment and nervous bridging. The aim of regenerative medicine, specifically tissue engineering, is to create a microenvironment that mimics native extracellular matrix (ECM), capable of promoting specific cell-matrix interactions, coaxing cell behavior, and fostering host tissue regeneration. In this regard, nanostructured scaffolds are currently the most promising advanced substrates capable of supporting nervous fiber ingrowth and delivery of neurotrophic drugs. Among them, electrospinning technique and Self-Assembling Peptides (SAPs) have recently attracted lots of attention for their reproducible synthesis and high tailorability. This review highlights clinical trials and recent encouraging strategies for spinal cord repair comprising both cell therapy and nanomedicine.

Regeneração pulpar como alternativa para tratamento endodôntico em dentes permanentes imaturos: revisão de literatura / Pulpal regeneration as an alternative for endodontic treatment in immature permanent teeth: literature review

A regeneração pulpar pode ser definida como a diferenciação de células progenitoras da porção apical de dentes jovens que resulta na deposição de tecido mineralizado nas paredes dentinárias. A endodontia regenerativa utiliza o conceito de engenharia de tecidos para restaurar os canais radiculares para um estado saudável, permitindo o desenvolvimento contínuo da raiz e tecidos circundantes. É uma alternativa terapêutica promissora que promove o fechamento apical e o desenvolvimento radicular e está indicada em dentes com formação incompleta de raízes, como alternativa à apicificação, um método para induzir uma barreira calcificada em uma raiz com ápice aberto ou desenvolvimento apical contínuo de uma raiz incompleta formada em dentes com polpas necróticas. No entanto, a presença de medicação por períodos prolongados de tempo pode levar a uma fragilidade das paredes radiculares. Devido a isso, há uma constante busca de novas alternativas de tratamento endodôntico que permita o desenvolvimento total da raiz. A regeneração emergiu como uma nova opção de tratamento para os jovens imaturos com necrose pulpar. Até à data, existem vários relatos na literatura de uma variedade de protocolos de tratamento para revascularização, sempre buscando alcançar a melhor maneira de sucesso do tratamento. Diante dessa variedade, é importante estudar a literatura sobre a regeneração da polpa. O objetivo deste estudo é revisar os protocolos na literatura para a regeneração da polpa, diferenciação celular e características do novo tecido formado

Pulp revascularization can be defined as a differentiation of progenitor cells from the apical portion of young teeth that results in deposition of mineralized tissue in the dentinal walls. Regenerative endodontics uses the concept od tissue engineering to restore the root canals to a healthy state, allowing for continued development of the root and surrounding tissue. It id a promising treatment alternative that promotes both apical closure and root development, and is indicated in teeth with incomplete root formation, as an alternative to apexification a method to induce a calcified barrier in a root with an open apex or the continued apical development of an incompletely formed root in teeth with necrotic pulps. However, the presence of medication for prolonged periods of time can lead to a fragility of the root walls. As a consequence there is a constant search for new alternatives of endodontic treatments that allow full root development. Regeneration has emerged as a new alternatives of endodontic treatment option for young immature teeth with pulp necrosis. To date, there are several reports in the literature of a variety of treatment protocols for revascularization, always seeking to anchive the best way to treatment success. In view of this variety, it is important to study the literature on pulp regeneration, cell differentiation and characteristics of the new tissue formed