Ti-based alloys are finding ever-increasing applications in biomaterials due to their excellent mechanical, physical and biological performance. Nowdays, low modulus β-type Ti-based alloys are still being developed. Meanwhile, porous Ti-based alloys are being developed as an alternative orthopedic implant material, as they can provide good biological fixation through bone tissue ingrowth into the porous network. This paper focuses on recent developments of biomedical Ti-based alloys. It can be divided into four main sections. The first section focuses on the fundamental requirements titanium biomaterial should fulfill and its market and application prospects. This section is followed by discussing basic phases, alloying elements and mechanical properties of low modulus β-type Ti-based alloys. Thermal treatment, grain size, texture and properties in Ti-based alloys and their limitations are dicussed in the third section. Finally, the fourth section reviews the influence of microstructural configurations on mechanical properties of porous Ti-based alloys and all known methods for fabricating porous Ti-based alloys. This section also reviews prospects and challenges of porous Ti-based alloys, emphasizing their current status, future opportunities and obstacles for expanded applications. Overall, efforts have been made to reveal the latest scenario of bulk and porous Ti-based materials for biomedical applications.

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New Developments of Ti-Based Alloys for Biomedical Applications

Calcium phosphate (CaP) bioceramics are widely used in the field of bone regeneration, both in orthopedics and in dentistry, due to their good biocompatibility, osseointegration and osteoconduction. The aim of this article is to review the history, structure, properties and clinical applications of these materials, whether they are in the form of bone cements, paste, scaffolds, or coatings. Major analytical techniques for characterization of CaPs, in vitro and in vivo tests, and the requirements of the US Food and Drug Administration (FDA) and international standards from CaP coatings on orthopedic and dental endosseous implants, are also summarized, along with the possible effect of sterilization on these materials. CaP coating technologies are summarized, with a focus on electrochemical processes. Theories on the formation of transient precursor phases in biomineralization, the dissolution and reprecipitation as bone of CaPs are discussed. A wide variety of CaPs are presented, from the individual phases to nano-CaP, biphasic and triphasic CaP formulations, composite CaP coatings and cements, functionally graded materials (FGMs), and antibacterial CaPs. We conclude by foreseeing the future of CaPs.

Calcium Phosphate Bioceramics: A Review of Their History, Structure, Properties, Coating Technologies and Biomedical Applications.

The current need for organ and tissue replacement, repair, and regeneration for patients is continually growing such that supply is not meeting demand primarily due to a paucity of donors as well as biocompatibility issues leading to immune rejection of the transplant. In order to overcome these drawbacks, scientists have investigated the use of scaffolds as an alternative to transplantation. These scaffolds are designed to mimic the extracellular matrix (ECM) by providing structural support as well as promoting attachment, proliferation, and differentiation with the ultimate goal of yielding functional tissues or organs. Initial attempts at developing scaffolds were problematic and subsequently inspired an interest in 3D printing as a mode for generating scaffolds. Utilizing three-dimensional printing (3DP) technologies, ECM-like scaffolds can be produced with a high degree of complexity, where fine details can be included at a micrometer level. In this Review, the criteria for printing viable and functional scaffolds, scaffolding materials, and 3DP technologies used to print scaffolds for tissue engineering are discussed. Creating biofunctional scaffolds could potentially help to meet the demand by patients for tissues and organs without having to wait or rely on donors for transplantation.

3D Printing of Scaffolds for Tissue Regeneration Applications

"Surgical Pathology of the Head and Neck, Third Edition " is a complete stand-alone reference dealing with head and neck pathology. Providing an interdisciplinary approach to the diagnosis, treatment, and management of head and neck diseases, and covering all aspects of general pathology - this is the reference of choice for head and neck pathologists, head and neck surgeons and pathologists promoting clear communication between pathologists and surgeons. With over 1200 photographs, micrographs, drawings, and tables - over 200 more illustrations than the second edition - head and neck pathologists, head and neck surgeons, otolaryngologists and pathologists will find this updated bestseller a valid reference for any practice. Unparalleled in scope and content than any other book available on the subject, "Surgical Pathology of the Head and Neck, Third Edition" is a must-have resource for oral, surgical, and general pathologists; otolaryngologists; oral, maxillofacial, plastic, reconstructive, general, head, neck, and orthopedic surgeons; and neurosurgeons, oncologists, hematologists, ophthalmologists, radiologists, endocrinologists, dermatologists, dentists, and residents and fellows in these disciplines.

Surgical Pathology of the Head and Neck

Background
The last few decades have seen a progressive shift in paradigm, replacing the notion of body implants as inert biomaterials for that of immune-modulating interactions with the host.

Purpose
This text represents an attempt at understanding the current knowledge on the healing mechanisms controlling implant–host interactions, thus interpreting osseointegration and the peri-implant bone loss phenomena also from an immunological point of view.

Materials and Methods
A narrative review approach was taken in the development of this article.

Results
Osseointegration, actually representing a foreign body reaction (FBR) to biomaterials, is an immune-modulated, multifactorial, and complex healing process where a number of cells and mediators are involved. The buildup of osseointegration seems to be an immunologically and inflammatory-driven process, with the ultimate end to shield off the foreign material placed in the body, triggered by surface protein adsorption, complement activation, and buildup of a fibrin matrix, followed by recruitment of granulocytes, mesenchymal stem cells, and monocytes/macrophages, with the latter largely controlling the longer term response, further fusing into foreign body giant cells (FBGC), while bone cells make and remodel hydroxyl apatite. The above sequence results in the FBR that we call osseointegration and use for clinical purposes. However, the long-term clinical function is dependent on a foreign body equilibrium, that if disturbed may lead to impaired clinical function of the implant, through a breakdown process where macrophages are again activated and may further fuse into FBGCs, now seen in much greater numbers, resulting in the start of bone resorption – due to cells such as osteoclasts with different origins and possibly even macrophages degrading more bone than what is formed via osteoblastic activity – and rupture of mucosal seals, through complex mechanisms in need of further understanding. Infection may follow as a secondary event, further complicating the clinical scenario. Implant failure may ensue.

Conclusions
Dentistry is still to embrace the concept of the biomaterials' healing- and immune-modulating effect when in contact with body tissues. The presented knowledge has the potential to open the door for a different interpretation of past, current, and future observations in dental implant science. From a clinical standpoint, it seems recommendable to react as rapidly as possible when facing peri-implant bone loss, trying to reestablish a foreign body equilibrium if with some bone resorption.

Foreign Body Reaction to Biomaterials: On Mechanisms for Buildup and Breakdown of Osseointegration.

A porous material for bone ingrowth with adequate pore structure and appropriate mechanical properties has long been sought as the ideal bone-implant interface. This study aimed to assess in vivo the influence of three types of porous titanium implant on the new bone ingrowth. The implants were produced by means of a powder metallurgy technique with different porosities and pore sizes: Group 1 = 30 % and 180 µm; Group 2 = 30% and 300 µm; and Group 3 = 40% and 180 µm;. Six rabbits received one implant of each type in the right and left tibiae and were sacrificed 8 weeks after surgery for histological and histomorphometric analyses. Histological analysis confirmed new bone in contact with the implant, formed in direction of pores. Histomorphometric evaluation demonstrated that the new bone formation was statistically significantly lower in the group G1 than in group G3, (P = 0.023). Based on these results, increased porosity and pore size were concluded to have a positive effect on the amount of bone ingrowth.

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Evaluation of bone ingrowth into porous titanium implant: histomorphometric analysis in rabbits.

Porous titanium scaffolds are promising materials for biomedical applications such as prosthetic anchors, fillers and bone reconstruction. This study evaluated the bone/titanium interface of scaffolds with interconnected pores prepared by powder metallurgy, using scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). Porous scaffolds and dense samples were implanted in the tibia of rabbits, which were subsequently killed 1, 4, and 8 weeks after surgery. Initial bone neoformation was observed one week after implantation. Bone ingrowth in pores and the Ca/P ratio at the interface were remarkably enhanced at 4 and 8 weeks. The results showed that the interconnected pores of the titanium scaffolds promoted bone ingrowth, which increased over time. The powder metallurgy technique thus proved effective in producing porous scaffolds and dense titanium for biomedical applications, allowing for adequate control of pore size and porosity and promoting bone ingrowth.

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Porous titanium scaffolds produced by powder metallurgy for biomedical applications

The purpose of this study was to analyze the bone repair around commercially pure titanium implants with rough and porous surface, fabricated using powder metallurgy technique, after their insertion in tibiae of rabbits. Seven male rabbits were used. Each animal received 3 porous-surface implants in the left tibia and 3 rough-surface implants in the right tibia. The rabbits were sacrificed 4 weeks after surgery and fragments of the tibiae containing the implants were submitted to histological and histomorphometric analyses to evaluate new bone formation at the implant-bone interface. Means (%) of bone neoformation obtained in the histomorphometric analysis were compared by Student's t-test for paired samples at 5% significance level.. The results of the histological analysis showed that osseointegration occurred for both types of implants with similar quality of bone tissue. The histomorphometric analysis revealed means of new bone formation at implant-bone interface of 79.69 ± 1.00% and 65.05 ± 1.23% for the porous- and rough-surface implants, respectively. Statistically significant difference was observed between the two types of implants with respect to the amount new bone formation (p<0.05). In conclusion, the porous-surface implants contributed to the osseointegration because they provide a larger contact area at implant-bone interface.

Histomorphometric analysis of pure titanium implants with porous surface versus rough surface

RESUMO HISTOMORPHOMETRIC ANALYSIS OF PURE TITANIUMIMPLANTS WITH POROUS SURFACE V ERSUS ROUGHSURFACE ANALISE HISTOMORFOMETRICA DE IMPLANTES DE TITÂNIO PURO COM SUPERFICIEPOROSA VERSUS SUPERFICIE RUGOSA Aline Scalone BRENTEL 1 , Luana Marotta Reis de VASCONCELLOS 2 , Marize Varella OLIVEIRA 3 , Mario Lima de AlencastroGRACA 4 , Luis Gustavo Oliveira de VASCONCELLOS 5 , Carlos Alberto Alves CAIRO 4 , Yasmin Rodarte CARVALHO 6 1- DDS, Undergraduate dental student, Department of Bioscience and Buccal Diagnosis, Sao Jose dos Campos Dental School, State Universityof Sao Paulo (UNESP), Sao Jose dos Campos, SP, Brazil.2- DDS, MSc, PhD, Graduate dental student, Department of Bioscience and Buccal Diagnosis, Sao Jose dos Campos Dental School, StateUniversity of Sao Paulo (UNESP), Sao Jose dos Campos, SP, Brazil.3- DDS, MSc, PhD, National Institute of Technology of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.4- DDS, MSc, PhD, Department of Materials of the Air and Space Institute, Aerospace Technical Center of Sao Jose dos Campos, Sao Jose dosCampos, SP, Brazil.5- DDS, Graduate dental student .6- DDS, MSc, PhD, Adjunctive Professor, Department of Bioscience and Buccal Diagnosis, Sao Jose dos Campos Dental School, StateUniversity of Sao Paulo (UNESP), Sao Jose dos Campos, SP, Brazil.

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Histomorphometric analysis of pure titanium implants with porous surface versus rough surface análise histomorfométrica de implantes de titânio puro com superfície porosa versus superfície rugosa

OBJECTIVE: To study the nature of multinucleated and mononuclear cells from peripheral giant cell granuloma (PGCG). MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded sections of 40 cases of PGCG were immunohistochemically stained for vimentin, alpha I-antichymotrypsin, CD68, S-100 protein, lysozyme, leucocyte common antigen (LCA), factor VIII-related antigen and muscle cell actin. Six cases of PGCG were also studied by transmission electron microscopy. RESULTS: Vimentin, alpha I-antichymotrypsin and CD68 were expressed in both the mononuclear and multinucleated giant cells. Dendritic mononuclear cells, positive for S-100 protein, were noted in 67.5% of the lesions, whereas lysozyme and leucocyte common antigen were detected in occasional mononuclear cells. Ultrastructural examination showed mononuclear cells with signs of phagocytosis and sometimes interdigitations with similar cells. Others presented non-specific characteristics and the third type exhibited cytoplasmic processes and occasional Birbeck granules. Some multinucleated giant cells showed oval nuclei, abundant mitochondria and granular endoplasmic reticulum whereas others presented with irregular nuclei and a great number of cytoplasmic vacuoles. CONCLUSIONS: Immunohistochemical and ultrastructural results suggest that PGCGs of the jaws are composed mainly of cells of the mononuclear phagocyte system and that Langerhans cells are present in two thirds of the lesions.

Yasmin Rodarte Carvalho

Papers

Evaluation of bone ingrowth into porous titanium implant: histomorphometric analysis in rabbits.

Porous titanium scaffolds produced by powder metallurgy for biomedical applications

Histomorphometric analysis of pure titanium implants with porous surface versus rough surface

Histomorphometric analysis of pure titanium implants with porous surface versus rough surface análise histomorfométrica de implantes de titânio puro com superfície porosa versus superfície rugosa

Peripheral giant cell granuloma. An immunohistochemical and ultrastructural study