The future perspectives of natural materials for pulmonary drug delivery and lung tissue engineering

Introduction: Search for new, functional biomaterials that can be used to synergistically deliver a drug, enhance its adsorption and stimulate the post-injury recovery of tissue function, is one of the priorities in biomedicine. Currently used materials for drug delivery fail to satisfy one or more of these functionalities, thus they have limited potential and new classes of materials are urgently needed.

Areas covered: Natural materials, due to their origin, physical and chemical structure can potentially fulfill these requirements and there is already strong evidence of their usefulness in drug delivery. They are increasingly utilized in various therapeutic applications due to the obvious advantages over synthetic materials. Particularly in pulmonary drug delivery, there have been limitations in the use of synthetic materials such as polymers and lipids, leading to an increase in the use of natural and protein-based materials such as silk, keratin, elastin and collagen. Literature search in each specialized field, namely, silk, keratin and collagen was conducted, and the benefits of each material for future application in pulmonary drug delivery are highlighted.

Expert opinion: The natural materials discussed in this review have been well established in their use for other applications, yet further studies are required in the application of pulmonary drug delivery. The properties exhibited by these natural materials seem positive for their application in lung tissue engineering, which may allow for more extensive testing for validation of pulmonary drug delivery systems.     

Pharmacotherapy of corneal transplantation

Introduction: Corneal transplantation is a surgical procedure in which damaged or diseased cornea is replaced by cadaveric corneal tissue. It is the most common form of solid-tissue transplantation in humans but its pharmacotherapy (in relation to graft rejection) has changed little for several decades. The mainstay of treatment of corneal graft rejection remains corticosteroids but these are variably effective and are associated with potentially serious adverse effects. Newer immunosuppressive drugs are increasingly being employed to manage high-risk grafts. However, these drugs are also not without side-effects, some of which can be severe and life-threatening.

Areas covered: This review outlines the corneal transplant procedure and the treatment options available in the management of transplant rejection.

Expert opinion: The surgical technique of corneal lamellar grafting has allowed for transplantation of smaller quantities of donor tissue to the recipient, thereby reducing the antigen load as a means of preventing a rejection episode. With greater understanding of the underlying molecular mechanisms involved in corneal transplant rejection pathology, potentially newer medications that will target specific cytokines or cells involved in rejection, whilst minimizing the potential side effects to the graft recipient, will be made available.     

Tissue engineering a small diameter vessel substitute: engineering constructs with select biomaterials and cells

Cardiovascular disease (CVD) is a leading cause of death and hospitalization worldwide. The need for small caliber vessels ( < 6mm) to treat CVD patients has grown; however the availability of autologous vessels in cardiac and peripheral bypass candidates is limited. The search for an alternative vessel source is widespread with both natural and synthetic tissue engineered materials being investigated as scaffolds. Despite decades of exhaustive studies with decellularized extracellular matrices (ECM) and synthetic graft materials, the field remains in search of a commercially viable biomaterial construct substitute. While the previous materials have been assessed by evaluating their compatibility with fibroblasts, smooth muscle cells and endothelial cells, current materials are being conceived based on their interactions with stem cells, progenitor cells and monocytes, as the latter may hold the key to repair and regeneration. The graft's ability to recruit and maintain these cells has become a major research focus. The successful tissue engineering of a small caliber vessel graft requires the use of optimal material chemistry and biological function to promote cell recruitment into the graft while maintaining each functional phenotype during vessel tissue maturation. The discussion of these significant research challenges constitutes the focus of this review.     

围手术期输注红细胞对不停跳下冠脉旁路移植术后近期桥血管通畅率的影响

目的 探讨不停跳下冠状动脉旁路移植术（OPCABG）围术期输入红细胞对于术后近期桥血管通畅率的影响。方法 选择2013年6月至2015年6月在安徽医科大学第一附属医院行OPCABG的106例（共127例,失访21例）患者为研究对象,依据患者围术期红细胞的使用与否分为两组：组Ⅰ（输注红细胞组,71例）;组Ⅱ（未输注红细胞组,35例）。术后1年左右行冠脉CT检查,对比观察两组患者各桥血管通畅情况。结果 组Ⅱ桥血管通畅率（96.97%）高于组Ⅰ（90.40%）,差异有统计学意义（P<0.05）,组Ⅱ大隐静脉桥血管通畅率（96.92%）高于组Ⅰ（88.15%）,差异有统计学意义（P<0.05）,而两组间乳内动脉桥血管通畅率比较差异无统计学意义（P>0.05）。结论 OPCABG围手术期输血会加大近期大隐静脉桥血管再狭窄的发生率。     

Tissue engineered buccal mucosa for urethroplasty: Progress and future directions

PurposeAutologous buccal mucosa is commonly utilized in the surgical treatment of urethral strictures. Extensive strictures require a larger quantity of tissue, which may lead to donor site morbidity. This review assesses progress in producing tissue engineered buccal mucosa as an alternative graft material.ResultsFew clinical studies have introduced cells onto biological or synthetic scaffolds and implanted resulting constructs in patients. The available studies show that buccal mucosa cells on acellular human dermis or on collagen matrix lead to good acute stage tissue integration. Urothelial cells on a synthetic substrate also perform well. However while some patients do well many years post-grafting, others develop stricture recurrence. Acellular biomaterials used to treat long urethral defects in animals commonly lead to fibrosis.ConclusionsTissue engineered buccal mucosa shows promise as a substitute for native tissue. The fibrosis which occurs months post-implantation may reflect the underlying disease process recurring in these patients.     

Nanoparticle technology in bone tissue engineering

Nanotechnology has been increasingly utilized to enhance bone tissue engineering strategies. In particular, nanotechnology has been employed to overcome some of the current limitations associated with bone regeneration methods including insufficient mechanical strength of scaffold materials, ineffective cell growth and osteogenic differentiation at the defect site, as well as unstable and insufficient production of growth factors to stimulate bone cell growth. Among the tremendous technologies of nanoparticles in biological systems, we focus here on the three major nanoparticle research areas that have been developed to overcome these limitations and disadvantages: (a) the generation of nanoparticle-composite scaffolds to provide increased mechanical strength for bone graft, (b) the fabrication of nanofibrous scaffolds to support cell growth and differentiation through morphologically-favored architectures, and (c) the development of novel delivery and targeting systems of genetic material, especially those encoding osteogenic growth factors. These nanoparticle-based bone tissue engineering technologies possess a great potential to ensure the efficacy of clinical bone regeneration.     

Delivery of steroids into the eye for the treatment of macular edema

ABSTRACT

Introduction: Steroids have been in extensive use in ophthalmology since their discovery in 1948. Steroids are effective for the treatment of macular edema and may be delivered into the eye either topically, systemically, subconjunctivally, sub-Tenon, intravitreally and through injectable sustained release devices. Various steroid formulations and devices are commercially available. Each carries advantages and disadvantages, which requires the ophthalmologist to exercise careful medical judgment upon treatment selection.

Areas covered: This article focuses in steroid delivery into the eye for the treatment of macular edema, and reviews the current and future treatment options, summarizing their clinical efficacy and possible adverse effects.

Expert opinion: Steroids have an important role in the treatment of macular edema, regardless of its cause. Steroids are efficacious, low-cost, and much clinical experience has been accumulated regarding their use over the years. Prolonged systemic steroid use may be associated with severe systemic and local side effects, directly proportional to dosage and time. Intravitreal delivery of steroids has gained popularity as the medication is administered close to the target tissue, significantly reducing the possibility of systemic adverse effects. The biggest problem associated with intravitreal steroids still remains unacceptably high risk of glaucoma and cataract formation. Various controlled-release intravitreal delivery devices are currently commercially available, and more are in the pipeline. While they still carry the risk of local side effects, they are efficacious and can control macular edema for months and years after a single administration.     

一期植骨外固定加灌洗修复下肢火器伤骨缺损

目的：评价一期植骨外固定和灌洗修复下肢火器伤骨缺损的疗效。方法：17例下肢火器伤长骨开放粉碎性骨折伴骨缺损，早期彻底清创，一期自体髂骨瓣植骨，外固定架固定，术后给予持续灌洗、抗生素治疗。结果：16例术后随访7－24个月，6－8周有骨痂形成，植骨与宿主骨愈合时间平均8个月，无骨不愈合发生。结论：外固定架在四肢长骨火器性损伤骨缺损治疗中具有独特的优越性，辅以自体髂骨植骨和术后持续灌洗可以一期修复伤口污染轻、软组织缺损少的火器性损伤。     

Protein- and peptide-based electrospun nanofibers in medical biomaterials

Electrospun fibers are being studied and developed because they hold considerable promise for realizing some advantages of nanostructured materials. The fibers can be made of biocompatible and biodegradable polymers. Electrospinning has therefore attracted interest in biotechnology and medicine, and there has been rapid growth in this area in recent years. This review presents an introduction to polymer nanofiber electrospinning, focusing on the use of natural proteins and synthetic peptides. We summarize key physical properties of protein-based and peptide-based nanofiber mats, survey biomedical applications of these materials, identify key challenges, and outline future prospects for development of the technology for tissue engineering, drug delivery, wound healing, and biosensors.From the Clinical EditorThis review focuses on polymer nanofiber electrospinning using natural proteins and synthetic peptides. The authors describe key properties and applications of these materials, and outline future prospects for tissue engineering, drug delivery, wound healing, and biosensors based on these nanomats and nanofibers.     

人工真皮加超薄皮片修复复杂性骨外露创面临床应用

目的 应用人工真皮加超薄皮片修复复杂性骨外露创面并评价其疗效.方法 选取安徽医科大学第二附属医院整形外科10例非功能部位的骨外露患者,采用人工真皮加超薄皮片移植修复,骨外露面积最大约10 cm×8 cm,最小约3 cm×2 cm.结果 10例皮片均成活良好,骨外露创面有效修复,愈合良好,供区瘢痕不明显. 结论 人工真皮加超薄皮片移植修复复杂性骨外露创面,为非功能部位骨外露创面提供一种新的治疗方法.     

Vessel graft atherosclerosis in murine models

The use of animal models in the study of arteriosclerosis is essential for better understanding of the pathogenesis, improvement in diagnosis, prevention and therapy of the diseases in humans. Recently numerous investigators started to use mouse models to study the pathogenesis of cardiovascular diseases. This species is particularly valuable which is believed to have some advantages over other strains, because of the availability of well-defined genetic systems of transgenic and knockout mice. Concomitantly, we have established the mouse models for vein grafts and transplant arteriosclerosis. By using these models, we have learned much knowledge concerning the pathogenesis of the disease and possible therapeutic intervention has been gained. One of most important findings is that proteins or molecules influencing apoptosis, inflammation or proliferation of vascular smooth muscle cells or endothelial cells, have been found to enhance or inhibit neointimal lesion formation in knockout or mutant mice in these models. Furthermore, the findings on the origins of endothelial and smooth muscle cells in lesions of vein graft and transplant atherosclerosis provided basic information that have challenged the traditional hypothesis. Using these models, it has also been demonstrated that stem cells identified in blood and bone marrow as well as the vasculature contribute to the atherosclerotic lesion formation, supporting the importance of murine models of vessel grafts in understanding the mechanisms of the vascular diseases. The present review updates the progress of the research in this field, by summarizing data of using mouse models of vessel grafts, and provides a perspective analysis on the future directions.     

Animal models for studying vein graft failure and therapeutic interventions

Vein grafts have been extensively used to bypass blockages in arteries, but are themselves subject to early closure by thrombosis or later obstruction by vein graft disease (neointimal hyperplasia and remodelling). Animal models are a crucial means of testing potential therapeutic and surgical interventions to prevent graft stenosis and occlusion. This review outlines many of the animal models of vein grafting. Recent studies include targeted gene therapy to prevent acute vein graft thrombosis and the use of folic acid to limit graft failure in diabetic pigs.     

Ceramic corundum materials with modified surface as implantation materials

Investigations on implants have proved that not only the kind of material structure, but also the surface character of grafts influences the local reaction of biomaterials. In recent years electrochemical reactions on implants surface leading to the so called zeta potential arouse interests. Applications of these properties has made us carry on experiments on use of biomaterials with active potential on their bio-compatibility. The aim of this work is evaluation of influence of electrical charge with zeta potentials character on the local reaction of bone tissue after implantation. Two kinds of ceramics were used in experiments: solid and solid-silane with active surface. Implantation experiments were made on 20 rabbits. Selections were carried of 12, 26, 36 and 54 weeks after implantation of the tested materials. After implantation of solid ceramics, not only bone tissue but also fibrous tissue was observed around the graft. But in case of solid silane ceramics, in all terms of tests, bone tissue tightly sticking to the implant was observed around the graft. Investigations of electrokinetic zeta potential carried out 36 and 54 weeks after implantation showed that the values of that potential originally introduced on the grafts surface were maintained on stable level. The carried out investigations confirmed that activation of implants surface through silaning with sol-gel method allows to introduce the planned zeta potential depending on the characteristic for a given kind of tissue.     

Effects of vaccinia virus anti-inflammatory protein 35K and TIMP-1 gene transfers on vein graft stenosis in rabbits

BACKGROUND: Vein graft stenosis is a common problem after bypass surgery. Vein grafts are ideal targets for gene therapy because transduction can be made ex vivo before grafting. Since chemokines and inflammatory factors are involved in vein graft thickening, we tested a hypothesis that the vaccinia virus anti-inflammatory protein 35K which can sequester CC-chemokines, can reduce vein graft thickening in vivo. MATERIALS AND METHODS: We used adenovirus-mediated gene transfer (1x10(9) pfu/ml) of 35K and compared its effects on reducing stenosis in a rabbit jugular vein graft model with tissue inhibitor of metalloproteinase-1 (TIMP-1) and LacZ control gene. TIMP-1 was used in this study because it has previously been shown to inhibit vein graft stenosis in other model systems. The expression of transgenes in the transduced segments was confirmed by RT-PCR. Vein grafts were analyzed using immunohistological and morphometric methods at the three-day time-point and at two-week and four-week time-points. RESULTS: It was found that the anti-inflammatory protein 35K was an efficient factor in reducing neointima formation at the two-week time-point, indicating that inflammatory factors play an important role in vein graft stenosis. At the four-week time-point, 35K still showed a reduced accumulation of macrophages. TIMP-1 also tended to reduce neointimal thickening at the two-week time-point as compared to LacZ. CONCLUSION: It was found that 35K is an efficient factor in reducing neointima formation, macrophage accumulation and proliferation in rabbit vein grafts after adenoviral ex vivo gene transfer.     

Targeted delivery as key for the success of small osteoinductive molecules

Molecules such as growth factors, peptides and small molecules can guide cellular behavior and are thus important for tissue engineering. They are rapidly emerging as promising compounds for the regeneration of tissues of the musculoskeletal system. Growth factors have disadvantages such as high cost, short half-life, supraphysiological amounts needed, etc. Therefore, small molecules may be an alternative. These molecules have been discovered using high throughput screening. Small osteoinductive molecules exhibit several advantages over growth factors owing to their small sizes, such as high stability and non-immunogenicity. These molecules may stimulate directly signaling pathways that are important for osteogenesis. However, systemic application doesn’t induce osteogenesis in most cases. Therefore, local administration is needed. This may be achieved by using a bone graft material providing additional osteoconductive properties. These graft materials can also act by themselves as a delivery matrix for targeted and local delivery. Furthermore, vascularization is necessary in the process of osteogenesis. Many of the small molecules are also capable of promoting vascularization of the tissue to be regenerated. Thus, in this review, special attention is given to molecules that are capable of inducing both angiogenesis and osteogenesis simultaneously. Finally, more recent preclinical and clinical uses in bone regeneration of those molecules are described, highlighting the needs for the clinical translation of these promising compounds.     

Oncologic,Endocrine & Metabolic Overview: Recent advances in implants for bone growth promotion

Devices intended for delivery of bone growth promoters should possess several properties. The device should have enough strength to hold the bone in place during the course of fixation, yet it should be biodegradable so that ultimately replacement by new bone will occur. This requires that the device has a certain level of porosity to allow for the ingrowth of new bone during the healing process. Many materials can be utilised for implants including naturally occurring materials (e.g., bone, fibrin, collagen) and synthetic materials (polymers, ceramics, metals). The appropriate material should be biocom-patible and not inhibit bone growth. Many approaches combining various active agents (e.g., bone morphogenic proteins, transforming growth factor, prostaglandins) with one of several synthetic or naturally occurring matrices have been examined. Several systems show promising initial results; however, the actual bone growth promoter release profiles required for efficacious treatment have not yet been established. In addition, the commercial viability of this type of device is highly dependent on the ability of the manufacturer to prepare the implants economically and reproducibly.     

Acellular matrix in urethral reconstruction

The treatment of severe urethral stenosis has always been a challenge even for skilled urologists. Classic urethroplasty, skin flaps and buccal mucosa grafting may not be used for long and complex strictures. In the quest for an ideal urethral substitute, acellular scaffolds have demonstrated the ability to induce tissue regeneration layer by layer. After several experimental studies, the use of acellular matrices for urethral reconstruction has become a clinical reality over the last decade. In this review we analyze advantages and limitations of both biological and polymeric scaffolds that have been reported in experimental and human studies. Important aspects such as graft extension, surgical technique and cell-seeding versus cell-free grafts will be discussed.     

Pharmacotherapy of corneal transplantation

INTRODUCTION: Corneal transplantation is a surgical procedure in which damaged or diseased cornea is replaced by cadaveric corneal tissue. It is the most common form of solid-tissue transplantation in humans but its pharmacotherapy (in relation to graft rejection) has changed little for several decades. The mainstay of treatment of corneal graft rejection remains corticosteroids but these are variably effective and are associated with potentially serious adverse effects. Newer immunosuppressive drugs are increasingly being employed to manage high-risk grafts. However, these drugs are also not without side-effects, some of which can be severe and life-threatening. AREAS COVERED: This review outlines the corneal transplant procedure and the treatment options available in the management of transplant rejection. EXPERT OPINION: The surgical technique of corneal lamellar grafting has allowed for transplantation of smaller quantities of donor tissue to the recipient, thereby reducing the antigen load as a means of preventing a rejection episode. With greater understanding of the underlying molecular mechanisms involved in corneal transplant rejection pathology, potentially newer medications that will target specific cytokines or cells involved in rejection, whilst minimizing the potential side effects to the graft recipient, will be made available.     

Use of A Reconstituted Human Skin Model for Predicting the Inflammation Potential of Wound Care Products

Abstract

United States Pharmacopoeia protocols for cytotoxicity are conducted using a monolayer of cultured rodent fibroblasts. Major disadvantages of these tests are that they are conducted with nonhuman cells and that noncytotoxic inflammatory events go undetected. In our studies a commercially available hydrogel wound dressing and povidone-iodine were dosed onto a reconstituted human skin model. Cytotoxicity was determined by punch biopsying dosed tissues and extracting a vital dye. Inflammation potential was assessed by measuring prostaglandin E₂ from the spent media of treated tissues. Results showed that povidone-iodine has a substantially greater potential to produce cytotoxicity and biochemical inflammation in human tissue than hydrogel wound dressing. This information may assist physicians in selecting the best treatment modality for wounds.     

脱细胞真皮与自体刃厚皮移植治疗瘢痕畸形

目的探讨用脱细胞真皮移植后代替自体真皮的效果。方法瘢痕切除时保留深筋膜上2~3mm脂肪组织,植入脱细胞真皮和自体刃厚皮,手术一次成功。结果本组35例,术后皮片全部成活,6例患者随访1年,皮肤弹性良好,触柔软,功能良好,供皮区可以多次供皮无瘢痕,节省自体皮源。结论形成的复合体达到厚皮片的效果,起到自体全厚皮的作用。