Soft and hard tissue response to endosseous dental implants

The last two decades have seen a remarkable growth in the development of dental implants and their incorporation into the practice of dentistry. This turn of events was made possible by an improved understanding of the biological response of living tissues to implants as well as clinical trials that validated the long-term success of these implants. Despite major structural differences between teeth and implants, such as the absence of a periodontal ligament around implants, the latter appear to provide a reliable functional replacement for their natural counterparts. This review briefly summarizes the major structural differences of the interfacial region of teeth and dental implants and their supporting tissues. It focuses on our current understanding of the soft and hard tissue responses to submerged and nonsubmerged root-form dental implants. The influence of a number of factors that affect the tissue response is reviewed, including biomaterials, implant design, surgical technique, and the local microbiota. Our recently acquired ability to modulate wound healing with guided tissue regeneration and growth factors will undoubtedly play an important role in the future utilization and success rates of dental implants. © 1996 Wiley-Liss, Inc.     

Mesenchymal stem cells in tissue engineering

The repair of diseased or damaged cartilage remains one of the most challenging problems of musculoskeletal medicine. Tissue engineering advances in cartilage repair have utilized autologous and allogenic chondrocyte and cartilage grafts, biomaterial scaffolds, growth factors, stem cells, and genetic engineering. The mesenchymal stem cell has specifically attracted much attention because of its accessibility, potential for differentiation, and manipulability to modern molecular, tissue and genetic engineering techniques. Mesenchymal stem cells provide invaluable tools for the study of tissue repair when combined with a carrier vehicle/matrix scaffold, and/or bioactive growth factors. However, an underappreciated source of knowledge lies in the relationship between fetal development and adult tissue repair. The multitude of events that take place during fetal development which lead from stem cell to functional tissue are poorly understood. A more thorough understanding of the events of development as they pertain to cartilage organogenesis may help elucidate some of the unknowns of adult tissue repair.     

A customized self-assembling peptide hydrogel for dental pulp tissue engineering

Root canal therapy is common practice in dentistry. During this procedure, the inflamed or necrotic dental pulp is removed and replaced with a synthetic material. However, recent research provides evidence that engineering of dental pulp and dentin is possible by using biologically driven approaches. As tissue engineering strategies hold the promise to soon supersede conventional root canal treatment, there is a need for customized scaffolds for stem cell delivery or recruitment. We hypothesize that the incorporation of dental pulp-derived stem cells with bioactive factors into such a scaffold can promote cell proliferation, differentiation, and angiogenesis. In this study, we used a cell adhesive, enzyme-cleavable hydrogel made from self-assembling peptide nanofibers to encapsulate dental pulp stem cells. The growth factors (GFs) fibroblast growth factor basic, transforming growth factor β1, and vascular endothelial growth factor were incorporated into the hydrogel via heparin binding. Release profiles were established, and the influence of GFs on cell morphology and proliferation was assessed to confirm their bioactivity after binding and subsequent release. Cell morphology and spreading in three-dimensional cultures were visualized by using cell tracker and histologic stains. Subcutaneous transplantation of the hydrogel within dentin cylinders into immunocompromised mice led to the formation of a vascularized soft connective tissue similar to dental pulp. These data support the use of this novel biomaterial as a highly promising candidate for future treatment concepts in regenerative endodontics.     

Biomaterial selection for tooth regeneration

Biomaterials are native or synthetic polymers that act as carriers for drug delivery or scaffolds for tissue regeneration. When implanted in vivo, biomaterials should be nontoxic and exert intended functions. For tooth regeneration, biomaterials have primarily served as a scaffold for (1) transplanted stem cells and/or (2) recruitment of endogenous stem cells. This article critically synthesizes our knowledge of biomaterial use in tooth regeneration, including the selection of native and/or synthetic polymers, three-dimensional scaffold fabrication, stem cell transplantation, and stem cell homing. A tooth is a complex biological organ. Tooth loss represents the most common organ failure. Tooth regeneration encompasses not only regrowth of an entire tooth as an organ, but also biological restoration of individual components of the tooth including enamel, dentin, cementum, or dental pulp. Regeneration of tooth root represents perhaps more near-term opportunities than the regeneration of the whole tooth. In the adult, a tooth owes its biological vitality, arguably more, to the root than the crown. Biomaterials are indispensible for the regeneration of tooth root, tooth crown, dental pulp, or an entire tooth.     

Status and potential commercial impact of stem cell-based treatments on dental and craniofacial regeneration

The projected annual demand for stem cell-based dental treatments in the United States can range from over 290 million tooth restorative treatments to 30,000 patients requiring tissue regeneration following craniofacial cancer surgery. Professional dental treatments cost Americans over $60 billion per year. Scientific advances in stem cell technologies, tissue engineering, and transplantation will provide the basis for the introduction of new treatment technologies into dentistry. This review provides an assessment of how stem cell therapies will likely change dental practice. The problems of introducing stem cell therapies are substantial, but they provide the best hope for many patients with congenital defects, and to regenerate teeth and tissues lost because of disease, cancer, and trauma, or missing because of congenital malformation. The most expensive dental treatments may be the most attractive candidates for stem cell therapies. This would indicate that craniofacial reconstruction, implants, and endodontic treatments are the most valuable applications of dental stem cell therapies, whereas tooth restorations and other dental treatments are the less commercially valuable.     

细胞力学机械刺激对牙髓干细胞的影响

文题释义：牙髓干细胞：通过GRONTHOS等对牙髓细胞的研究,发现一种具有与间充质干细胞相似免疫表型和形成矿化结节能力的细胞,称为牙髓干细胞,具有自我更新、多向分化和较强的克隆能力。细胞力学：研究细胞在力学载荷作用下细胞膜和细胞骨架的变形、弹性常数、黏弹性、黏附力等力学性质,以及机械因素对细胞生长、发育、成熟、增殖、分化、衰老和死亡等的影响及其机制研究,是生物力学的一个前沿领域,也是组织工程学的一个重要组成部分。  摘要背景：力学刺激对于机体内很多器官、组织的发育和损伤修复发挥重要的调控作用。除生物化学因素外,细胞力学等机械因素越来越被认为是影响牙髓干细胞行为和功能的关键调节因素。目的：综述细胞力学刺激对牙髓干细胞生物学行为的作用及影响。方法：通过检索PubMed、Embase、Medline、CNKI数据库,分别以“牙髓干细胞,机械压力,机械张力,剪切力,压应力,细胞增殖,成骨分化”为中文检索词和“human dental pulp stem cells(hDPSCs),mechanical strain,mechanical stretch,mechanical tension,shear stress,cell proliferation,osteogenesis differentiation”为英文检索词进行检索,选取与细胞力学机械刺激参与影响牙髓干细胞增殖、分化的56篇文献进行综述。结果与结论：细胞力学机械刺激是影响细胞增殖、分化、蛋白表达和凋亡的重要生物学因素。牙髓干细胞是牙髓组织中的间充质干细胞,其生物学行为也受到细胞力学机械刺激的影响。细胞力学刺激参与牙髓干细胞的增殖、成牙/成骨分化,并且当牙本质受到流体流动力作用时,会激活其机械感受器来调节并维持牙齿的完整性。介导牙髓干细胞生物学行为的信号通路包括MAPK、Wnt、Akt及BMP-7、Nrf2/HO-1等,通过调控这些信号通路进而对牙髓干细胞增殖及成牙/成骨分化发挥不同程度的促进及抑制作用。ORCID: 0000-0001-6191-6539(李峻青) 中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

New perspectives on tooth development and the dental stem cell niche

Adult stem cells have the capacity to self-renew and differentiate along multiple lineages in addition to contributing to ongoing tissue maintenance and regeneration after injury. They reside in specific locations called stem cell niches. In biology of the tooth, the discovery of dental epithelial stem cells in continuously growing teeth has been a recent breakthrough. The niche for the adult stem cells of these teeth is formed at the region of the apical end in tooth development. The region possesses a commonly specialized histological structure for the maintenance of adult stem cells and the production of various progenitor cells producing dental tissues. The molecular signals regulating the maintenance and cell fate decision of adult stem cells, such as Notch1, Lunatic fringe, fibroblast growth factor (FGF)-10, are expressed in the epithelial structure and the surrounding mesenchyme. Based on histological and molecular biological studies, we propose a new concept that the eternal tooth buds producing various dental progeny are formed at the apical end in the development of continuously growing teeth, and coin a new term of "apical bud" for indicating this specialized epithelial structure. Furthermore, the relationship between signaling centers and the expression of FGF-10 mRNA as the determinant of morphogenesis is discussed with an emphasis on tooth and limb development, taking note that the expression pattern of FGF-10 is an important key for understanding the mechanisms for the diversity of cusp patterns and between continuous and limited growth.     

Genomic Profiling of Mesenchymal Stem Cells

Mesenchymal stem/stromal cells (MSC) are an accessible source of precursor cells that can be expanded in vitro and used for tissue regeneration for different clinical applications. The advent of microarray technology has enabled the monitoring of individual and global gene expression patterns across multiple cell populations. Thus, genomic profiling has fundamentally changed our capacity to characterize MSCs, identify potential biomarkers and determined key molecules regulating biological processes involved in stem cell survival, growth and development. Numerous studies have now examined the genomic profiles of MSCs derived from different tissues that exhibit varying levels of differentiation and proliferation potentials. The knowledge gained from these studies will help improve our understanding of the cellular signalling pathways involved in MSC growth, survival and differentiation, and may aid in the development of strategies to improve the tissue regeneration potential of MSCs for different clinical indications. The present review summarizes studies characterizing the gene expression profile of MSCs.     

酶解组织块法原代培养人牙周膜干细胞和牙髓干细胞

背景：酶解组织法是一种高效的原代细胞培养方法,利用该法可提高牙周膜干细胞和牙髓干细胞的培养成功率。 目的：比较牙周膜干细胞和牙髓干细胞的原代培养成功率、细胞形态、生长特征,并对其进行多种细胞标志的鉴定。 方法：取因正畸需要拔除健康牙20颗,其中16颗用于牙周膜干细胞原代培养,4颗用于牙髓干细胞培养。酶解组织块法培养两种细胞,MTT法检测两种细胞的生长曲线,利用RT-PCR法、细胞免疫组化法、细胞免疫荧光法鉴定两种细胞的标志。 结果与结论：牙髓干细胞的原代培养成功率明显高于牙周膜干细胞,显示更快的生长能力。通过酶解组织法分离纯化的两种干细胞均显示正常的细胞形态和生长特征,表达相应的细胞标志CD105,CD73,波形丝蛋白vimitin,Stro-1,不表达角蛋白CK-17和CD45。提示酶解组织块法是一种高效的原代培养牙周膜干细胞和牙髓干细胞的方法。     

牙髓干细胞在组织工程研究中的应用

背景：牙髓干细胞是来源于牙髓组织中的一种成体干细胞,该种细胞具有高度增殖、自我更新的能力和多向分化潜能。通过对牙髓干细胞的深入研究,有助于人类为组织工程研究提供可能的细胞来源,进而指导临床相关治疗与预防。 目的：就牙髓干细胞的研究现状及其在组织工程中的应用作一综述。 方法：应用计算机检索CNKI和Pubmed数据库中2000年1月至2012年5月关于牙髓干细胞的文章,在标题和摘要中以“牙髓干细胞,诱导,培养,分化”或“dental pulp stem cells,culture,induced,differentiation”为检索词进行检索。选择文章内容与牙髓干细胞有关者,同一领域文献则选择近期发表或发表在权威杂志文章。初检得到205篇文献,根据纳入标准选择关于牙周局部缓释剂的44篇文献进行综述。 结果与结论：相比较其他成体干细胞,牙髓干细胞的研究尚面临许多问题。但随着科学技术的日益进步,随着这些问题的深入探讨和逐步解决,牙髓干细胞的研究将日趋完善。牙髓干细胞有望成为牙组织工程、骨组织工程和神经组织工程的种子细胞,在牙髓再生、牙体的修复等方面有着广阔的应用前景。     

Stem Cells and Muscle Diseases

In the past recent years, basic science work and initial clinical trials have provided starting evidence that stem cells are of potential value for treatment of certain human diseases, where they could help to regenerate tissues which are defective because of either genetic or acquired diseases. This area represents an emerging field of biomedicine based on a series of new discoveries in the field of stem cell biology and developmental biology that have made possible to isolate and expand stem cells from many human tissues. Additional evidence has also revealed the role of tissue environment that, by releasing a complex mixture of cytokines and growth factors, can influence the recruitment and functional integration of stem cells into specific organs. However, there is an urgent need for more advancement in basic biology of stem cells and related topics, which will be instrumental for the implementation of stem cell-based therapy at the clinical level, as treatment accessibility will depend on the acquisition of sufficient knowledge to develop adequate technologies to produce sufficient cell numbers and to drive their differentiating potentials.     

牙周膜干细胞与牙周组织的再生

背景：牙周组织再生过程中再生细胞数量和生物学功能的不足是造成组织再生困难的主要原因。 目的：就近年来牙周膜干细胞在牙周组织再生中的研究进展及未来展望作一综述。 方法：由第一作者检索Pubmed 数据库(http://www.ncbi.nlm.nih.gov/pubmed)、中国知网数据库(http://www. cnki.net/)2000年1月至2012年7月 有关牙周膜干细胞分离、鉴定、相关细胞因子等方面的文献,英文检索词为“periodontal ligamentstem cell”,中文检索词为“牙周膜,干细胞”。排除重复性研究,最终纳入26 篇文献进行综述。 结果与结论：利用组织工程的方法,将牙周膜干细胞作为牙周组织再生的种子细胞,在体外培养扩增后移植至缺损区,可有效增进牙周附着结构的再生并缩短愈合周期。对牙周膜干细胞的研究已成为目前牙组织工程领域中的重点课题。     

Therapeutic ultrasound for dental tissue repair

Dental disease affects human health and the quality of life of millions worldwide. Tooth decay (caries) and diseases of the dental pulp result in loss of tooth vitality and function requiring invasive treatment to restore the tooth to health. “Therapeutic” low intensity pulsed ultrasound has been shown to accelerate bone fracture healing indicating that ultrasound may be used as a tool to facilitate hard tissue regeneration. We have shown recently that low frequency ultrasound is able to exert biological effects on odontoblast-like cells. In this paper, we postulate that low frequency, low intensity ultrasound may stimulate endogenous coronal tooth repair by stimulating dentine formation from existing odontoblasts or by activating dental pulp stem cells to differentiate into new reparative dentine-producing cells. Ultrasound therapy promoting dentine formation and repair may also have the potential benefit of alleviating dentine hypersensitivity by inducing occlusion of dentinal tubules. It is envisaged that therapeutic ultrasound may be used in future to facilitate dental tissue engineering and stem cell therapy applications for dental tissue regeneration. Further research is warranted in this clinically important area and we envisage that novel strategies in dental therapy will be realised that may ultimately lead to the development of novel non-invasive, multifunctional ultrasound devices for dental diagnostics, repair and regeneration.     

Hematopoietic Stem Cell Homing to Injured Tissues

The use of stem cells is considered a promising therapy for tissue regeneration and repair, particularly for tissues injured through degeneration, ischemia and inflammation. Bone marrow (BM)-derived haematopoietic stem cells (HSCs) are rare populations of multipotent stem cells that have been identified as promising potential candidates for treating a broad range of conditions. Although research into the use of stem cells for regenerative medicine is on a steep upward slope, clinical success has not been as forthcoming. This has been primarily attributed to a lack of information on the basic biology of stem cells, which remains insufficient to justify clinical studies. In particular, while our knowledge on the molecular adhesive mechanisms and local environmental factors governing stem cell homing to BM is detailed, our understanding of the mechanisms utilized at injured sites is very limited. For instance, it is unclear whether mechanisms used at injured sites are location specific or whether this recruitment can be modulated for therapeutic purposes. In addition, it has recently been suggested that platelets may play an important role in stem cell recruitment to sites of injury. A better understanding of the mechanisms used by stem cells during tissue homing would allow us to develop strategies to improve recruitment of these rare cells. This review will focus on the status of our current understanding of stem cell homing to injured tissues, the role of platelets and directions for the future.     

Natural ECM as Biomaterial for Scaffold Based Cardiac Regeneration Using Adult Bone Marrow Derived Stem Cells

Cellular therapy using stem cells for cardiac diseases has recently gained much interest in the scientific community due to its potential in regenerating damaged and even dead tissue and thereby restoring the organ function. Stem cells from various sources and origin are being currently used for regeneration studies directly or along with differentiation inducing agents. Long term survival and minimal side effects can be attained by using autologous cells and reduced use of inducing agents. Cardiomyogenic differentiation of adult derived stem cells has been previously reported using various inducing agents but the use of a potentially harmful DNA demethylating agent 5-azacytidine (5-azaC) has been found to be critical in almost all studies. Alternate inducing factors and conditions/stimulant like physical condition including electrical stimulation, chemical inducers and biological agents have been attempted by numerous groups to induce cardiac differentiation. Biomaterials were initially used as artificial scaffold in in vitro studies and later as a delivery vehicle. Natural ECM is the ideal biological scaffold since it contains all the components of the tissue from which it was derived except for the living cells. Constructive remodeling can be performed using such natural ECM scaffolds and stem cells since, the cells can be delivered to the site of infraction and once delivered the cells adhere and are not “lost”. Due to the niche like conditions of ECM, stem cells tend to differentiate into tissue specific cells and attain several characteristics similar to that of functional cells even in absence of any directed differentiation using external inducers. The development of niche mimicking biomaterials and hybrid biomaterial can further advance directed differentiation without specific induction. The mechanical and electrical integration of these materials to the functional tissue is a problem to be addressed. The search for the perfect extracellular matrix for therapeutic applications including engineering cardiac tissue structures for post ischemic cardiac tissue regeneration continues.     

Stem cell responses in tooth regeneration

Scientific advances in the creation of restorative biomaterials, in vitro cell culture technology, tissue grafting, tissue engineering, molecular biology, and the human genome project provide the basis for the introduction of new technologies into dentistry. This review is intended to facilitate the development of stem cell therapy for use with established therapeutic modalities to restore and regenerate oral tissues. Teeth have been shown to mineralize in response to injury for many decades, but only in recent years has the position of the stem cells been localized around blood vessels. The cells have been identified as myofibroblastoid pericytes. The ability to control the differentiation and proliferation of these cells is being examined to create stem cell therapies that can solve dental problems more effectively than current treatment regimes. Although the problems of introducing these technologies are substantial, the potential benefits to patients and the profession are equally promising - a cure for caries and diseases, a cure for oral cancer, correction of congenital defects, and the regeneration of teeth and tissues to restore oral functions. The purpose of this review is to describe how these new technologies can most usefully be employed in dentistry to enable clinicians to satisfy patient demand for a nondefective dentition.     

Stem Cells in Tooth Tissue Regeneration—Challenges and Limitations

The accelerated pace of research in the stem cell field in recent decades and the accumulated body of knowledge has spurred the interest in potential clinical applications of stem cells in all branches of medicine including regenerative dentistry. In humans, embryonic and adult stem cells are two major groups of cells that can serve as a donor source in tissue engineering strategies based on ex-vivo cellular expansion. It has been shown that adult stem cell populations are present in all examined living tissues of the organism, thus being a crucial source of tissue homeostasis and regeneration, and offering a target population for in situ stimulation of extensive tissue regeneration. Experimental findings indicate that in the complex structure of the tooth organ, both periodontal and endodontic tissues harbour adult stem cells with characteristics peculiar to early stages of cellular differentiation. Myriad of strategies incorporating both embryonic and adult stem cells for the regeneration of a particular tooth structure or the whole teeth were proposed; however their successful application to solve real problems encountered in the clinical practice of dentistry remains an elusive and challenging objective.     

口腔颌面外科领域组织工程学研究进展

口腔颌面组织工程研究是人体组织工程学研究一个重要组成部分。口腔颅颌面部集中了皮肤、粘膜、肌肉、骨骼、神经、腺体、牙齿、关节等诸多组织和器官 ,具有很大组织工程学研究价值、制品需求潜力和广阔的临床应用前景。同时 ,口腔颌面各组织器官由于其结构和功能上的特殊性 ,具有突出的区别于机体其它部位的组织工程学研究特点。本文将从牙齿、牙周、种植牙、唾液腺、颞颌关节、腭裂修复、皮肤粘膜、口腔颌面骨组织工程。以及基因工程与组织技术的联合应用等方面介绍近几年来国际国内口腔颌面外科领域的组织工程学研究进展。     

Cellular signaling in tissue regeneration

With recent progress in stem cell-based research, there has been tremendous interest in stem cell-based tissue regeneration. Stem cells can be differentiated into specialized cells/tissues by growth factors and cytokines. These small molecules are thought to play an important role in both wound healing and tissue regeneration. However, their biological activity and signal transduction during tissue regeneration are poorly understood. With recent advances in signal transduction by growth factors, the receptor kinases and G protein-coupled receptors, an understanding in the underlying mechanism of how these factors regulate tissue regeneration beginning to take place. In this review, the potential underlying mechanisms of growth factor signaling in normal tissue regeneration and chronic wound healing is discussed. Thus, it is an aim to provide a basis for designing more specific therapies for tissue regeneration in the near future.