Nanostructured Biomaterials for Tissue Engineered Bone Tissue Reconstruction

Bone tissue engineering strategies are emerging as attractive alternatives to autografts and allografts in bone tissue reconstruction, in particular thanks to their association with nanotechnologies. Nanostructured biomaterials, indeed, mimic the extracellular matrix (ECM) of the natural bone, creating an artificial microenvironment that promotes cell adhesion, proliferation and differentiation. At the same time, the possibility to easily isolate mesenchymal stem cells (MSCs) from different adult tissues together with their multi-lineage differentiation potential makes them an interesting tool in the field of bone tissue engineering. This review gives an overview of the most promising nanostructured biomaterials, used alone or in combination with MSCs, which could in future be employed as bone substitutes. Recent works indicate that composite scaffolds made of ceramics/metals or ceramics/polymers are undoubtedly more effective than the single counterparts in terms of osteoconductivity, osteogenicity and osteoinductivity. A better understanding of the interactions between MSCs and nanostructured biomaterials will surely contribute to the progress of bone tissue engineering

Biomaterial based modulation of macrophage polarization: a review and suggested design principles

Macrophages have long been known for their phagocytic capabilities and immune defence; however, their role in healing is being increasingly recognized in recent years due to their ability to polarize into pro-inflammatory and anti-inflammatory phenotypes. Historically, biomaterials were designed to be inert to minimize the host response. More recently, the emergence of tissue engineering and regenerative medicine has led to the design of biomaterials that interact with the host through tailored mechanical, chemical and temporal characteristics. Due to such advances in biomaterial functionality and an improved understanding of macrophage responses to implanted materials, it is now possible to identify biomaterial design characteristics that dictate the host response and contribute to successful tissue integration. Herein, we begin by briefly reviewing macrophage cell origin and the key cytokine/chemokine markers of macrophage polarization and then describe which responses are favorable for both replacement and regenerative biomaterials. The body of the review focuses on macrophage polarization in response to inherent cues directly provided by biomaterials and the consequent cuesthat result from events related to biomaterial implantation. To conclude, a section on potential design principles for both replacement and regenerative biomaterials is presented. An in depth understanding of biomaterial cues to selectively polarize macrophages may prove beneficial in the design of a new generation of ‘immuno-informed’ biomaterials that can positively interact with the immune system to dictate a favorable macrophage response following implantation

Preparação e caracterização de um biocompósito obtido pela mistura de hidreto de titânio com nitrato de cálcio para implantes dentários

RESUMO Neste trabalho foram realizados estudos sobre a fabricação de um biocompósito à base de titânio para implantes dentários a partir da mistura de pó de hidreto de titânio (92%) com nitrato de cálcio (8% em volume). O pó de hidreto de titânio foi adicionado na solução aquosa de nitrato de cálcio, dissolvido por agitação mecânica, e em seguida os precursores foram misturados e dispersados/homogeneizados por ultrassom. Posteriormente, a mistura foi secada em evaporador rotativo, compactada com 600 MPa à temperatura ambiente, desmoldada e sinterizada em alto vácuo a 1200 oC durante 2 horas. Foi analisada a microestrutrura e fases formadas, as propriedades mecânicas, a rugosidade da superfície, a porosidade aberta, a molhabilidade da superfície e a citotoxicidade do biocompósito. As fases identificadas após a sinterização foram α-Ti e CaTiO3. O limite de resistência em compressão, o módulo de Young (E) e o ângulo de contato do biocompósito diminuíram significativamente com relação ao hidreto de titânio puro sinterizado nas mesmas condições. O limite médio de resistência em compressão do hidreto de titânio foi de 1794,67 MPa e do biocompósito foi de 481,36 MPa. O módulo de Young e o ângulo de contato do hidreto de titânio e do biocompósito foram de aproximadamente 112 GPa e 94 graus, e de 75 GPa e 83 graus, respectivamente. A rugosidade de superfície foi da mesma ordem de grandeza entre os materiais e ficou aproximadamente entre 1,4 e 1,5 µm (Ra) e 1,4 e 1,9 µm (Ra e Sa), medidas com rugosímetro de contato e com microscópio confocal a laser, respectivamente. A porosidade aberta do biocompósito sinterizado foi de aproximadamente três vezes maior do que aquela do hidreto de titânio sinterizado. Nos ensaios de citotoxicidade a porcentagem de células viáveis do biocompósito foi superior àquela do controle negativo e àquela do hidreto de titânio sinterizado

In Vivo Ectopic Implantation Model to Assess Human Mesenchymal Progenitor Cell Potential

Clinical interest on human mesenchymal progenitor cells (hMPC) relies on their potential applicability in cell-based therapies. An in vitro characterization is usually performed in order to define MPC potency. However, in vitro predictions not always correlate with in vivo results and thus there is no consensus in how to really assess cell potency. Our goal was to provide an in vivo testing method to define cell behavior before therapeutic usage, especially for bone tissue engineering applications. In this context, we wondered whether bone marrow stromal cells (hBMSC) would proceed in an osteogenic microenvironment. Based on previous approaches, we developed a fibrin/ceramic/BMP-2/hBMSCs compound. We implanted the compound during only 2 weeks in NOD-SCID mice, either orthotopically to assess its osteoinductive property or subcutaneously to analyze its adequacy as a cell potency testing method. Using fluorescent cell labeling and immunohistochemistry techniques, we could ascertain cell differentiation to bone, bone marrow, cartilage, adipocyte and fibrous tissue. We observed differences in cell potential among different batches of hBMSCs, which did not strictly correlate with in vitro analyses. Our data indicate that the method we have developed is reliable, rapid and reproducible to define cell potency, and may be useful for testing cells destined to bone tissue engineering purposes. Additionally, results obtained with hMPCs from other sources indicate that our method is suitable for testing any potentially implantable mesenchymal cell. Finally, we propose that this model could successfully be employed for bone marrow niche and bone tumor studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12015-013-9464-1) contains supplementary material, which is available to authorized users

A Review of Bioceramics and Fibrin Sealant

This review focuses on bone substitute composites made by mixing ceramic biomaterials with fibrin sealants. Different biomaterials such as coral, bone-derived materials, bioactive glass ceramics, and synthetic calcium phosphate have been mixed with fibrin sealant, resulting in a combination of the biological properties of the two components. This type of association has not produced identical results in all studies. In the past for some, the addition of fibrin sealant to the biomaterial failed to produce any significant, positive effect on osteointegration, whereas others found a positive impact on bone colonization. Despite the negative biological effects reported previously, bioceramic-fibrin composites have been widely used in various types of bone surgery because they are easy to manipulate. In particular, the intra-operative preparation of these composites makes it possible to add bone growth factors or autologous osteoprogenitor cells prior to bone reconstruction. The bone growth factors and autologous osteoprogenitor cells associated with the bioceramic-fibrin composites should provide surgeons with tissue engineered grafts with enhanced osteointegrative properties. This review discusses both the advantages and disadvantages, as well as the future perspectives, of using bioceramic-fibrin composites in various clinical indications

Surface treatments of titanium dental implants for rapid osseointegration.

The osseointegration rate of titanium dental implants is related to their composition and surface roughness. Rough-surfaced implants favor both bone anchoring and biomechanical stability. Osteoconductive calcium phosphate coatings promote bone healing and apposition, leading to the rapid biological fixation of implants. The different methods used for increasing surface roughness or applying osteoconductive coatings to titanium dental implants are reviewed. Surface treatments, such as titanium plasma-spraying, grit-blasting, acid-etching, anodization or calcium phosphate coatings, and their corresponding surface morphologies and properties are described. Most of these surfaces are commercially available and have proven clinical efficacy (>95% over 5 years). The precise role of surface chemistry and topography on the early events in dental implant osseointegration remain poorly understood. In addition, comparative clinical studies with different implant surfaces are rarely performed. The future of dental implantology should aim to develop surfaces with controlled and standardized topography or chemistry. This approach will be the only way to understand the interactions between proteins, cells and tissues, and implant surfaces. The local release of bone stimulating or resorptive drugs in the peri-implant region may also respond to difficult clinical situations with poor bone quality and quantity. These therapeutic strategies should ultimately enhance the osseointegration process of dental implants for their immediate loading and long-term success