3D bioactive composite scaffolds for bone tissue engineering.

The Guided Bone Regeneration (GBR) treatment concept advocates that regeneration of osseous defects is predictably attainable via the application of occlusive membranes, which mechanically exclude non-osteogenic cell populations from the surrounding soft tissues, thereby allowing osteogenic cell populations originating from the parent bone to inhabit the osseous wound. The present review discusses the evolution of the GBR biological rationale and therapeutic concept over the last two decades. Further, an overview of the GBR research history is provided with specific focus on the evidence available on its effectiveness and predictability in promoting the regeneration of critical size cranio-maxillo-facial defects, the neo-osteogenesis potential and the reconstruction of atrophic alveolar ridges before, or in conjunction with, the placement of dental implants. The authors conclude that future research should focus on (a) the investigation of the molecular mechanisms underlying the wound healing process following GBR application; (b) the identification of site and patient related factors which impact on the effectiveness and predictability of GBR therapy and (c) the evaluation of the pathophysiology of the GBR healing process in the presence of systemic conditions potentially affecting the skeletal system.To cite this article:Retzepi M, Donos N. Guided Bone Regeneration: biological principle and therapeutic applications.Clin. Oral Impl. Res. 21, 2010; 567-576.doi: 10.1111/j.1600-0501.2010.01922.x.

Guided Bone Regeneration: biological principle and therapeutic applications

Collagen, the most abundant extracellular matrix protein in animal kingdom belongs to a family of fibrous proteins, which transfer load in tissues and which provide a highly biocompatible environment for cells. This high biocompatibility makes collagen a perfect biomaterial for implantable medical products and scaffolds for in vitro testing systems. To manufacture collagen based solutions, porous sponges, membranes and threads for surgical and dental purposes or cell culture matrices, collagen rich tissues as skin and tendon of mammals are intensively processed by physical and chemical means. Other tissues such as pericardium and intestine are more gently decellularized while maintaining their complex collagenous architectures. Tissue processing technologies are organized as a series of steps, which are combined in different ways to manufacture structurally versatile materials with varying properties in strength, stability against temperature and enzymatic degradation and cellular response. Complex structures are achieved by combined technologies. Different drying techniques are performed with sterilisation steps and the preparation of porous structures simultaneously. Chemical crosslinking is combined with casting steps as spinning, moulding or additive manufacturing techniques. Important progress is expected by using collagen based bio-inks, which can be formed into 3D structures and combined with live cells. This review will give an overview of the technological principles of processing collagen rich tissues down to collagen hydrolysates and the methods to rebuild differently shaped products. The effects of the processing steps on the final materials properties are discussed especially with regard to the thermal and the physical properties and the susceptibility to enzymatic degradation. These properties are key features for biological and clinical application, handling and metabolization.

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Processing of collagen based biomaterials and the resulting materials properties.

Graphene, graphene oxide, and reduced graphene oxide have been widely considered as promising candidates for industrial and biomedical applications due to their exceptionally high mechanical stiffness and strength, excellent electrical conductivity, high optical transparency, and good biocompatibility. In this article, we reviewed several techniques that are available for the synthesis of graphene-based nanomaterials, and discussed the biocompatibility and toxicity of such nanomaterials upon exposure to mammalian cells under in vitro and in vivo conditions. Various synthesis strategies have been developed for their fabrication, generating graphene nanomaterials with different chemical and physical properties. As such, their interactions with cells and organs are altered accordingly. Conflicting results relating biocompatibility and cytotoxicity induced by graphene nanomaterials have been reported in the literature. In particular, graphene nanomaterials that are used for in vitro cell culture and in vivo animal models may contain toxic chemical residuals, thereby interfering graphene-cell interactions and complicating interpretation of experimental results. Synthesized techniques, such as liquid phase exfoliation and wet chemical oxidation, often required toxic organic solvents, surfactants, strong acids, and oxidants for exfoliating graphite flakes. Those organic molecules and inorganic impurities that are retained in final graphene products can interact with biological cells and tissues, inducing toxicity or causing cell death eventually. The residual contaminants can cause a higher risk of graphene-induced toxicity in biological cells. This adverse effect may be partly responsible for the discrepancies between various studies in the literature.

https://www.mdpi.com/1422-0067/19/11/3564/pdf

Graphene Nanomaterials: Synthesis, Biocompatibility, and Cytotoxicity.

Despite considerable advances in microsurgical techniques over the past decades, bone tissue remains a challenging arena to obtain a satisfying functional and structural restoration after damage. Through the production of substituting materials mimicking the physical and biological properties of the healthy tissue, tissue engineering strategies address an urgent clinical need for therapeutic alternatives to bone autografts. By virtue of their structural versatility, polymers have a predominant role in generating the biodegradable matrices that hold the cells in situ to sustain the growth of new tissue until integration into the transplantation area (i.e., scaffolds). As compared to synthetic ones, polymers of natural origin generally present superior biocompatibility and bioactivity. Their assembly and further engineering give rise to a wide plethora of advanced supporting materials, accounting for systems based on hydrogels or scaffolds with either fibrous or porous architecture. The present review offers an overview of the various types of natural polymers currently adopted in bone tissue engineering, describing their manufacturing techniques and procedures of functionalization with active biomolecules, and listing the advantages and disadvantages in their respective use in order to critically compare their actual applicability potential. Their combination to other classes of materials (such as micro and nanomaterials) and other innovative strategies to reproduce physiological bone microenvironments in a more faithful way are also illustrated. The regeneration outcomes achieved in vitro and in vivo when the scaffolds are enriched with different cell types, as well as the preliminary clinical applications are presented, before the prospects in this research field are finally discussed. The collection of studies herein considered confirms that advances in natural polymer research will be determinant in designing translatable materials for efficient tissue regeneration with forthcoming impact expected in the treatment of bone defects.

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Natural Polymeric Scaffolds in Bone Regeneration

Polymer membranes have been widely used in guided tissue regeneration (GTR) and guided bone regeneration (GBR). In this review, various commercially available membranes are described. Much attention is paid to the recent development of biodegradable polymers applied in GTR and GBR, and the important issues of biodegradable polymeric membranes, including their classification, latest experimental research and clinical applications, as well as their main challenges are addressed. Herein, natural polymers, synthetic polymers and their blends are all introduced. Pure polymer membranes are biodegradable and biocompatible, but they lack special properties such as antibacterial properties, osteoconductivity, and thus polymer membranes loaded with functional materials such as antibacterial agents and growth factors show many more advantages and have also been introduced in this review. Despite there still being complaints about polymer membranes, such as their low mechanical properties, uncontrollable degradation speed and some other drawbacks, these problems will undoubtedly be conquered and biodegradable polymers will have more applications in GTR and GBR.

Hanjian Lai

Papers

Biodegradable Polymer Membranes Applied in Guided Bone/Tissue Regeneration: A Review.