Tendon tissue engineering using scaffold enhancing strategies

Tendon traumas or diseases are prevalent and debilitating lesions that affect the quality of life among populations worldwide. As a novel solution, tendon tissue engineering aims to address these lesions by integrating engineered, living substitutes with their native counterparts in vivo, thereby restoring the defective functions in situ. For such a purpose, competent scaffolding materials are essential. To date, three major categories of scaffolding materials have been employed: polyesters, polysaccharides, and collagen derivatives. Furthermore, with these materials as a base, a variety of specialized methodologies have been developed or adopted to enhance neo-tendogenesis. These strategies include cellular hybridization, interfacing improvement, and physical stimulation.     

Nanoscale engineering of extracellular matrix-mimetic bioadhesive surfaces and implants for tissue engineering

Background

The goal of tissue engineering is to restore tissue function using biomimetic scaffolds which direct desired cell fates such as attachment, proliferation and differentiation. Cell behavior in vivo is determined by a complex interaction of cells with extracellular biosignals, many of which exist on a nanoscale. Therefore, recent efforts in tissue engineering biomaterial development have focused on incorporating extracellular matrix- (ECM) derived peptides or proteins into biomaterials in order to mimic natural ECM. Concurrent advances in nanotechnology have also made it possible to manipulate protein and peptide presentation on surfaces on a nanoscale level.

Scope of Review

This review discusses protein and peptide nanopatterning techniques and examples of how nanoscale engineering of bioadhesive materials may enhance outcomes for regenerative medicine.

Major Conclusions

Synergy between ECM-mimetic tissue engineering and nanotechnology fields can be found in three major strategies: (1) Mimicking nanoscale orientation of ECM peptide domains to maintain native bioactivity, (2) Presenting adhesive peptides at unnaturally high densities, and (3) Engineering multivalent ECM-derived peptide constructs.

General Significance

Combining bioadhesion and nanopatterning technologies to allow nanoscale control of adhesive motifs on the cell–material interface may result in exciting advances in tissue engineering.This article is part of a Special Issue entitled Nanotechnologies - Emerging Applications in Biomedicine.     

Design concepts and strategies for tissue engineering scaffolds

In the emerging field of tissue engineering and regenerative medicine, new viable and functional tissue is fabricated from living cells cultured on an artificial matrix in a simulated biological environment. It is evident that the specific requirements for the three main components, cells, scaffold materials, and the culture environment, are very different, depending on the type of cells and the organ-specific application. Identifying the variables within each of these components is a complex and challenging assignment, but there do exist general requirements for designing and fabricating tissue engineering scaffolds. Therefore, this review explores one of the three main components, namely, the key concepts, important parameters, and required characteristics related to the development and evaluation of tissue engineering scaffolds. An array of different design strategies will be discussed, which include mimicking the extra cellular matrix, responding to the need for mass transport, predicting the structural architecture, ensuring adequate initial mechanical integrity, modifying the surface chemistry and topography to provide cell signaling, and anticipating the material selection so as to predict the required rate of bioresorption. In addition, this review considers the major challenge of achieving adequate vascularization in tissue engineering constructs, without which no three-dimensional thick tissue such as the heart, liver, and kidney can remain viable.     

Gene transfer strategies in tissue engineering

Aiming for regeneration of severed or lost parts of the body, the combined application of gene therapy and tissue engineering has received much attention by regenerative medicine. Techniques of molecular biology can enhance the regenerative potential of a biomaterial by co-delivery of therapeutic genes, and several different strategies have been used to achieve that goal. Possibilities for application are many-fold and have been investigated to regenerate tissues such as skin, cartilage, bone, nerve, liver, pancreas and blood vessels. This review discusses advantages and problems encountered with the different gene delivery strategies as far as they relate to tissue engineering, analyses the positive aspects of polymeric gene delivery from matrices and discusses advances and future challenges of gene transfer strategies in selected tissues.     

Orchestrating cell/material interactions for tissue engineering of surgical implants

Research groups are currently recognising a critical clinical need for innovative approaches to organ failure and agenesis. Allografting, autologous reconstruction and prosthetics are hampered with severe limitations. Pertinently, readily available 'laboratory-grown' organs and implants are becoming a reality. Tissue engineering constructs vary in their design complexity depending on the specific structural and functional demands. Expeditious methods on integrating autologous stem cells onto nanoarchitectured 3D nanocomposites, are being transferred from lab to patients with a number of successful first-in-man experiences. Despite the need for a complete understanding of cell/material interactions tissue engineering is offering a plethora of exciting possibilities in regenerative medicine.     

Present clinical applications of osseointegrated percutaneous implants

Altogether, 389 screws of commercially pure titanium have been inserted at various locations in the facial skeleton of 174 patients. The indications for treatment have been stable anchorage of an external hearing aid or a facial episthesis, in the latter case to restore the facial contours after congenital disorders or status after trauma or cancer surgery. All implants have been inserted in a two-stage procedure, the first being anchorage of the titanium elements in the bone, the second, minimally 3 months later, being establishment of a permanent skin penetration. The outcome of every inserted implant has been analyzed. Only six implants failed to become integrated in bone and had to be removed. Five of these failures occurred in previously irradiated bone, where the success rate was estimated to 85.3 percent. In nonirradiated bone, 354 of 355 inserted implants became osseointegrated, i.e., anchored in bone in a stable manner. The soft tissues were without any adverse reactions in 92 percent of the 951 clinical observations, whereas potentially serious skin complications were observed in only 2.8 percent. Presently, the longest clinical follow-up is 8 years, and 37 implants have been followed for more than 5 years. We believe that this clinical material is the first in which an uneventful bone anchorage and skin penetration have been demonstrated in consecutively operated upon clinical cases. The implants used for anchoring an external hearing aid were also successful in the sense that the patients gained 15 dB (average) in hearing threshold and showed a significantly improved discrimination score. The implants inserted to hold facial epistheses resulted in considerably improved retention and a good cosmetic outcome for the patients.     

Rehabilitation with ear prosthesis linked to osseointegrated implants

doi: 10.1111/j.1741‐2358.2011.00612.x Rehabilitation with ear prosthesis linked to osseointegrated implants Background: The absence of an ear, which can be the result of a congenital malformation, surgical tumour resection or traumatic injury, is a significant aesthetic problem. Attachment of ear prostheses with adhesives can cause local irritation for the wearer and affect the colour of the prostheses. Use of implants in craniofacial reconstruction can improve the retention and stability of prostheses giving to patient greater comfort and security relative to adhesive attachment. Objective: The aim of this report was to present a clinical case of a mutilated patient who was rehabilitated by means of installing an ear prosthesis fixed through osseointegrated implants. Materials and methods: The patient had two implants installed in the mastoid region that were linked by a bar, and a clip‐type system was used. The ear prosthesis was constructed from medical‐use silicone, pigmented to match the patient’s skin colour and linked to the retention system. Conclusion: The patient’s rehabilitation was satisfactory from both a functional and an aesthetic point of view, making it possible for the patient to return to a normal social life and regain lost self‐esteem.     

Functional reconstruction after a total maxillectomy using a fibula osteocutaneous flap with osseointegrated implants

The fibula osteocutaneous flap with osseointegrated implants was used for reconstruction of a total maxillectomy defect. We have achieved satisfactory reconstruction of three-dimensional facial structure, orbit support, and a functional prosthesis. Our procedure restored the patient's masticatory function of the maxilla and enabled good speech and a natural facial appearance. A very high quality of function was obtained without any complications, but long-term follow-up is necessary for maintenance of the implants.     

Osteochondral tissue engineering: Current strategies and challenges

Osteochondral defect management and repair remain a significant challenge in orthopedic surgery. Osteochondral defects contain damage to both the articular cartilage as well as the underlying subchondral bone. In order to repair an osteochondral defect the needs of the bone, cartilage and the bone-cartilage interface must be taken into account. Current clinical treatments for the repair of osteochondral defects have only been palliative, not curative. Tissue engineering has emerged as a potential alternative as it can be effectively used to regenerate bone, cartilage and the bone-cartilage interface. Several scaffold strategies, such as single phase, layered, and recently graded structures have been developed and evaluated for osteochondral defect repair. Also, as a potential cell source, tissue specific cells and progenitor cells are widely studied in cell culture models, as well with the osteochondral scaffolds in vitro and in vivo. Novel factor strategies being developed, including single factor, multi-factor, or controlled factor release in a graded fashion, not only assist bone and cartilage regeneration, but also establish osteochondral interface formation. The field of tissue engineering has made great strides, however further research needs to be carried out to make this strategy a clinical reality. In this review, we summarize current tissue engineering strategies, including scaffold design, bioreactor use, as well as cell and factor based approaches and recent developments for osteochondral defect repair. In addition, we discuss various challenges that need to be addressed in years to come.     

Characterization of pediatric microtia cartilage: a reservoir of chondrocytes for auricular reconstruction using tissue engineering strategies

The external ear is composed of elastic cartilage. Microtia is a congenital malformation of the external ear that involves a small reduction in size or a complete absence. The aim of tissue engineering is to regenerate tissues and organs clinically implantable based on the utilization of cells and biomaterials. Remnants from microtia represent a source of cells for auricular reconstruction using tissue engineering. To examine the macromolecular architecture of microtia cartilage and behavior of chondrocytes, in order to enrich the knowledge of this type of cartilage as a cell reservoir. Auricular cartilage remnants were obtained from pediatric patients with microtia undergoing reconstructive procedures. Extracellular matrix composition was characterized using immunofluorescence and histological staining methods. Chondrocytes were isolated and expanded in vitro using a mechanical-enzymatic protocol. Chondrocyte phenotype was analyzed using qualitative PCR. Microtia cartilage preserves structural organization similar to healthy elastic cartilage. Extracellular matrix is composed of typical cartilage proteins such as type II collagen, elastin and proteoglycans. Chondrocytes displayed morphological features similar to chondrocytes derived from healthy cartilage, expressing SOX9, COL2 and ELN, thus preserving chondral phenotype. Cell viability was 94.6 % during in vitro expansion. Elastic cartilage from microtia has similar characteristics, both architectural and biochemical to healthy cartilage. We confirmed the suitability of microtia remnant as a reservoir of chondrocytes with potential to be expanded in vitro, maintaining phenotypical features and viability. Microtia remnants are an accessible source of autologous cells for auricular reconstruction using tissue engineering strategies.     

Textured-surface saline-filled silicone breast implants for augmentation mammaplasty

The earliest silicone breast implants were smooth-surface, silicone rubber devices filled with either silicone gel or saline. Because of persistent problems with capsular contracture, polyurethane-covered silicone implants were developed as an alternative. Particularly in the short run, these alternatives proved highly successful at reducing the incidence of capsular contracture. By 1990, polyurethane-covered implants were rapidly becoming the preferred implant choice of many plastic surgeons, but for legal, regulatory, financial, and safety reasons they were withdrawn from the market by Bristol-Myers in 1991. Meanwhile, during the late 1980s, surface texturing and improved materials became available on other silicone breast implants and expanders. Most studies suggest that textured-surface silicone gel-filled implants, saline-filled implants, and tissue expanders have less frequent capsular contracture than their smooth-surface counterparts.     

Current and emerging vascularization strategies in skin tissue engineering

Vascularization is a key process in skin tissue engineering, determining the biological function of artificial skin implants. Hence, efficient vascularization strategies are a major prerequisite for the safe application of these implants in clinical practice. Current approaches include (i) modification of structural and physicochemical properties of dermal scaffolds, (ii) biological scaffold activation with growth factor-releasing systems or gene vectors, and (iii) generation of prevascularized skin substitutes by seeding scaffolds with vessel-forming cells. These conventional approaches may be further supplemented by emerging strategies, such as transplantation of adipose tissue-derived microvascular fragments, 3D bioprinting and microfluidics, miRNA modulation, cell sheet engineering, and fabrication of photosynthetic scaffolds. The successful translation of these vascularization strategies from bench to bedside may pave the way for a broad clinical implementation of skin tissue engineering.     

Tissue engineering strategies for the induction of angiogenesis using biomaterials

Angiogenesis is touted as a fundamental procedure in the regeneration and restoration of different tissues. The induction of de novo blood vessels seems to be vital to yield a successful cell transplantation rate loaded on various scaffolds. Scaffolds are natural or artificial substances that are considered as one of the means for delivering, aligning, maintaining cell connection in a favor of angiogenesis. In addition to the potential role of distinct scaffold type on vascularization, the application of some strategies such as genetic manipulation, and conjugation of pro-angiogenic factors could intensify angiogenesis potential. In the current review, we focused on the status of numerous scaffolds applicable in the field of vascular biology. Also, different strategies and priming approaches useful for the induction of pro-angiogenic signaling pathways were highlighted.     

静电纺丝法构建食道上皮组织

为了模拟食道上皮基膜构造,促进上皮组织的再生,以聚乳酸 (PLA) 和丝素蛋白 (SF) 为材料,利用静电纺丝法制备了PLA及PLA/SF等多孔纤维膜支架;并从猪食道粘膜组织中分离提取包括IV型胶原蛋白、层粘连蛋白、巢蛋白及蛋白聚糖等基膜蛋白的提取液,涂覆接枝于支架表面。通过扫描电镜 (SEM)、力学测试系统、体外降解等手段对支架材料的特征和性能进行检测。结果显示这两种支架的力学性能、纤维特性等均与基膜相仿;而细胞培养实验与CK14抗体进行的免疫组化分析表明,PLA/SF相对于PLA支架更能促进上皮细胞的增殖和粘附,基膜蛋白提取液的包被是有利于上皮细胞的生长和功能表达,研究结果将为工程化食道的构建提供重要的实验依据。     

Human iPSC-derived cardiomyocytes and tissue engineering strategies for disease modeling and drug screening

Improved methodologies for modeling cardiac disease phenotypes and accurately screening the efficacy and toxicity of potential therapeutic compounds are actively being sought to advance drug development and improve disease modeling capabilities. To that end, much recent effort has been devoted to the development of novel engineered biomimetic cardiac tissue platforms that accurately recapitulate the structure and function of the human myocardium. Within the field of cardiac engineering, induced pluripotent stem cells (iPSCs) are an exciting tool that offer the potential to advance the current state of the art, as they are derived from somatic cells, enabling the development of personalized medical strategies and patient specific disease models. Here we review different aspects of iPSC-based cardiac engineering technologies. We highlight methods for producing iPSC-derived cardiomyocytes (iPSC-CMs) and discuss their application to compound efficacy/toxicity screening and in vitro modeling of prevalent cardiac diseases. Special attention is paid to the application of micro- and nano-engineering techniques for the development of novel iPSC-CM based platforms and their potential to advance current preclinical screening modalities.     

Rat lung decellularization using chemical detergents for lung tissue engineering

Although pulmonary diseases account for a large number of deaths in the world, most have no treatment other than transplantation. New therapeutic methods for lung treatment include lung tissue engineering and regenerative medicine. Lung decellularization has been used to produce an appropriate scaffold for recellularization and implantation. We investigated 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate (CHAPS) with sodium dodecyl sulfate (SDS) and Triton X-100 detergents for effecting rat lung decellularization. We evaluated using conventional histology, immunofluorescence staining and SEM methods for removing nuclear material while leaving intact extracellular matrix proteins and three-dimensional architecture. We investigated different concentrations of CHAPS, SDS and Triton X-100 for different periods. We found that 2 mM CHAPS + 0/1% SDS for 48 h was the best among the treatments investigated. Our method can be used to produce an appropriate scaffold for recellularization by stem cells and for investigations ex vivo and in vivo.     

The safety and efficacy of breast implants for augmentation mammaplasty

This review of the efficacy and safety of breast implants was intended to focus on our current body of knowledge about these devices. There are informational gaps, but not all of these can be laid at the door of imperfect studies or failed scientific methods. Certain properties of the implants are still unmeasurable, immunologic investigation is still evolving, the cause of wound contraction is inexplicable here or in the burnscar contracture, and the indications for and results of this surgery necessarily are subjective. Still, there are a number of investigative avenues open to us, and our cumulative experience shows no reluctance on the part of plastic surgeons to initiate further studies.