The Use of Bone Substitutes in the Treatment of Bone Defects – the Clinical View and History

Summary: Bone has the ability to regenerate and remodel itself. In the clinic circumstances appear when bone defects do not heal spontaneously. These situations frequently result from trauma, congenital abnormities, infection or tumor resection. Hence, filling of the resulting defect by bone transplantation is a common practise with an increasing value in the re-establishment of the musculoskeletal system to promote bone healing. Since decades, efforts have been put to improve the effectiveness of bone substitutes. Conventional approaches with the use of ivory, animal and also human bone were not satisfactory. Negative effects like allergic reactions, rejection reactions, inflammations and other problems occurred. These led to implant failure, non union and amputation, to only mention a few. The introduction of bone banks and the development of standards in bone transplantation brought up the false hope to find a final solution for the treatment of bone loss. Disease transmissions (HIV) by allografts caused critical discussions. Despite all efforts, transplantation of autogenous cancellous bone is still the “gold standard” to induce bone healing. However, autografts are only limited available and are accompanied with high morbidity and mortality during the harvest. The problems associated with autologous and allogenous bone grafts promoted the development of multiple organic and inorganic bone substitutes. Well established substitutes at the present are demineralised bone matrix (DBM), composites and calcium phosphates (hydroxyl apatite and tri-calcium phosphate). These osteoconductive substances have shown to improve new bone formation. Nevertheless, clinical application of these materials is merely successful in a good bony environment but does not induce large progress in critical bone defects.     

Clinical Application of Resorbable Polymers in Guided Bone Regeneration

Summary : Guided bone regeneration was shown to be successful in vitro and in vivo using resorbable or nonresorbable materials. Resorbable material has the advantage of progressive substitution by bone. Resorbable polymers of ∝-hydroxy acids like polylactide or polyglycolide are commonly used for tissue engineering and in guided bone regeneration. In clinical studies, guided bone regeneration was successful in non-weight bearing bone, e.g. in dental surgery and craniofacial surgery. This paper reports the preliminary result of using resorbable poly(L/DL-lactide) 80/20% scaffolds in weight bearing bone with infected large segmental defects as well as in small bony defects of hand due to benign tumour, bone graft donor sites and as an adjunct for joint fusion. Resorbable polylactide implants were used in the form of membranes, large 3-D sponges, chips or as injectable paste. Implants were impregnated with marrow blood to add an osteoinductive component. Long-term follow up revealed that these implants are promising candidates for bone graft substitutes.     

Bone Dimensional Change Following Immediate Implant Placement in Posterior Teeth with CBCT: A 6-Month Prospective Clinical Study

This prospective clinical study aimed to evaluate the peri-implant hard tissue dimensional change at 6 months of immediate implant placement with bone graft materials in the posterior area using cone-beam computed tomography (CBCT). Twelve dental implants were placed concurrently following tooth extraction in the posterior area and filled with xenograft particles. The CBCT images were taken immediately after surgical procedures and then at 6 months follow-up. To evaluate the hard tissue changes, the vertical and horizontal bone thickness were analyzed and measured using ImageJ software. Paired t-test or Wilcoxon match-pair signed-rank test was done to analyze the changes of hard tissue values at the same level between immediately and 6 months following immediate implant placement. Independent t-test or Mann–Whitney U test was used to analyze the dimensional change in the vertical and horizontal direction in buccal and lingual aspects. The level of significance was set at p value = 0.05. All implants were successfully osseointegrated. At 6 months follow-up, the vertical bone change at the buccal aspect was −0.69 mm and at the lingual aspect −0.39 mm. For horizontal bone thickness, the bone dimensional changes at 0, 1, 5, and 9 mm levels from the implant platform were −0.62 mm, −0.70 mm, −0.24 mm, and −0.22 mm, respectively. A significant bone reduction was observed in all measurement levels during the 6 months after implant placement (p value < 0.05). It was noted that even with bone grafting, a decrease in bone thickness was seen following the immediate implant placement. Therefore, this technique can be an alternative method to place the implant in the posterior area.     

Development of Calcium Phosphate Glass-Ceramics for Surgical and Dental Use

Abstract

Two types of glass-ceramics have been developed in the system of calcium phosphate without silica. The preparation conditions, crystallization processes, and some of physical properties are briefly reported. These glass-ceramics have high potential use for bone substitutes and dental materials such as dental crown, root and tooth.     

On the Future Design of Bio‐Inspired Polyetheretherketone Dental Implants

Polyetheretherketone (PEEK) is a promising implant material because of its excellent mechanical characteristics. Although this polymer is a standard material in spinal applications, PEEK is not in use in the manufacturing of dental implants, where titanium is still the most‐used material. This may be caused by its relative bio‐inertness. By the use of various surface modification techniques, efforts have been made to enhance its osseointegrative characteristics to enable the polymer to be used in dentistry. In this feature paper, the state‐of‐the‐art for dental implants is given and different surface modification techniques of PEEK are discussed. The focus will lie on a covalently attached surface layer mimicking natural bone. The usage of such covalently anchored biomimetic composite materials combines many advantageous properties: A biocompatible organic matrix and a mineral component provide the cells with a surrounding close to natural bone. Bone‐related cells may not recognize the implant as a foreign body and therefore, may heal and integrate faster and more firmly. Because neither metal‐based nor ceramics are ideal material candidates for a dental implant, the combination of PEEK and a covalently anchored mineralized biopolymer layer may be the start of the desired evolution in dental surgery.     

Hydrogels as Scaffolds in Bone-Related Tissue Engineering and Regeneration

Several years have passed since the medical and scientific communities leaned toward tissue engineering as the most promising field to aid bone diseases and defects resulting from degenerative conditions or trauma. Owing to their histocompatibility and non-immunogenicity, bone grafts, precisely autografts, have long been the gold standard in bone tissue therapies. However, due to issues associated with grafting, especially the surgical risks and soaring prices of the procedures, alternatives are being extensively sought and researched. Fibrous and non-fibrous materials, synthetic substitutes, or cell-based products are just a few examples of research directions explored as potential solutions. A very promising subgroup of these replacements involves hydrogels. Biomaterials resembling the bone extracellular matrix and therefore acting as 3D scaffolds, providing the appropriate mechanical support and basis for cell growth and tissue regeneration. Additional possibility of using various stimuli in the form of growth factors, cells, etc., within the hydrogel structure, extends their use as bioactive agent delivery platforms and acts in favor of their further directed development. The aim of this review is to bring the reader closer to the fascinating subject of hydrogel scaffolds and present the potential of these materials, applied in bone and cartilage tissue engineering and regeneration.     

Induction of Osseointegration by Nacre in Pigs

Nacre is a biomaterial that has shown osteoinductive and osteoconductive properties in vitro and in vivo. These properties make nacre a material of interest for inducing bone regeneration. However, information is very limited regarding the introduction of nacre to dental implant surgery for promoting osteogenesis. This study investigated the potential of nacre powder for peri-implant bone regeneration in a porcine model. Ninety-six dental implants were placed into the tibia of twelve male domestic pigs. The dental implants were coated with nacre powder from the giant oyster before implantation. Implantations without nacre powder were used as control groups. Euthanization took place at 2, 4 and 6 weeks after implantation, after which we measured bone-to-implant contact (BIC) and bone volume density (BVD) of the implanted bone samples using micro-computed tomography (micro-CT), and examined the histology of the surrounding bone using histological sections stained with Stevenel’s blue and Alizarin red S. The micro-CT analyses showed that the BIC of dental implantations with nacre powder were significantly higher than those without nacre powder, by 7.60%. BVD of implantations with nacre powder were significantly higher than those without nacre powder, by 12.48% to 13.66% in cortical bone, and by 3.37% to 6.11% in spongy bone. Histological study revealed more peri-implant bone regeneration toward the surface of the dental implants after implantation with nacre powder. This was consistent with the micro-CT results. This study demonstrates the feasibility of using nacre to promote peri-implant bone regeneration in dental implantation.     

New Approaches in the Treatment of Critical-Size Segmental Defects in Long Bones

Summary : The treatment of large segmental diaphyseal bone deficiencies presents a formidable challenge. The standard treatment modalities such as cancellous bone grafting, cortical allografts, vascularized bone transfer, or distraction osteogenesis exhibit extremely high complication rates, and can culminate in limb amputation or major functional deficits. Recent efforts to develop new treatment modalities for segmental bone loss have resulted in designing new biodegradable polymeric and metallic mesh implants that can incorporate novel osteogenic, osteoinductive, and/or osteoconductive bone healing augmentation materials. These biologic implant composites are capable of further enhancing the efficacy of the treatment applied. This paper briefly reviews the limitations of the currently applied standard treatment modalities for segmental critical size bone defects, provides insight into the specific treatment challenges, and presents the animal and initial clinical results of new alterative treatment approaches that involve the application of cylindrical mesh implants consisting of biodegradable polylactide membranes or titanium cages as a means of potentiating the efficacy of bone graft.     

Applications of Biodegradable Magnesium-Based Materials in Reconstructive Oral and Maxillofacial Surgery: A Review

Reconstruction of defects in the maxillofacial region following traumatic injuries, craniofacial deformities, defects from tumor removal, or infections in the maxillofacial area represents a major challenge for surgeons. Various materials have been studied for the reconstruction of defects in the maxillofacial area. Biodegradable metals have been widely researched due to their excellent biological properties. Magnesium (Mg) and Mg-based materials have been extensively studied for tissue regeneration procedures due to biodegradability, mechanical characteristics, osteogenic capacity, biocompatibility, and antibacterial properties. The aim of this review was to analyze and discuss the applications of Mg and Mg-based materials in reconstructive oral and maxillofacial surgery in the fields of guided bone regeneration, dental implantology, fixation of facial bone fractures and soft tissue regeneration.     

Applications of Polydopamine in Implant Surface Modification

There is great clinical demand for orthopedic and dental implant surface modification methods to prevent osseointegration failure and improve implant biological functions. Notably, dopamine (DA) can be polymerized to form polydopamine (PDA), which is similar to the adhesive proteins secreted by mussels, to form a stable bond between the bone surface and implants. Therefore, PDA has the potential to be used as an implant surface modification material with good hydrophilicity, roughness, morphology, mechanical strength, biocompatibility, antibacterial activity, cellular adhesion, and osteogenesis. In addition, PDA degradation releases DA into the surrounding microenvironment, which is found to play an important role in regulating DA receptors on both osteoblasts and osteoclasts during the bone remodeling process. Furthermore, the adhesion properties of PDA suggest its use as an intermediate layer in assisting other functional bone remodeling materials, such as nanoparticles, growth factors, peptides, and hydrogels, to form “dual modifications.” The purpose of this review is to summarize the recent progress in research on PDA and its derivatives as orthopedic and dental implant surface modification materials and to analyze the multiple functions of PDA.     

The Role of Epigenetic Functionalization of Implants and Biomaterials in Osseointegration and Bone Regeneration—A Review

The contribution of epigenetic mechanisms as a potential treatment model has been observed in cancer and autoimmune/inflammatory diseases. This review aims to put forward the epigenetic mechanisms as a promising strategy in implant surface functionalization and modification of biomaterials, to promote better osseointegration and bone regeneration, and could be applicable for alveolar bone regeneration and osseointegration in the future. Materials and Methods: Electronic and manual searches of the literature in PubMed, MEDLINE, and EMBASE were conducted, using a specific search strategy limited to publications in the last 5 years to identify preclinical studies in order to address the following focused questions: (i) Which, if any, are the epigenetic mechanisms used to functionalize implant surfaces to achieve better osseointegration? (ii) Which, if any, are the epigenetic mechanisms used to functionalize biomaterials to achieve better bone regeneration? Results: Findings from several studies have emphasized the role of miRNAs in functionalizing implants surfaces and biomaterials to promote osseointegration and bone regeneration, respectively. However, there are scarce data on the role of DNA methylation and histone modifications for these specific applications, despite being commonly applied in cancer research. Conclusions: Studies over the past few years have demonstrated that biomaterials are immunomodulatory rather than inert materials. In this context, epigenetics can act as next generation of advanced treatment tools for future regenerative techniques. Yet, there is a need to evaluate the efficacy/cost effectiveness of these techniques in comparison to current standards of care.     

有机-无机杂化骨修复材料

寻找理想的骨修复材料一直是骨科领域的研究热点之一。骨修复材料已由最初单纯取代天然骨组织的惰性材料向具有诱导骨组织再生功能的生物活性材料发展,其中有机-无机杂化材料由于有机和无机组分在分子/纳米水平的复合使其能够最大程度地实现二者的优势互补和协同优化,近年来受到广泛关注。本文着重介绍了有机-无机杂化骨修复材料近些年来的研究进展,并对其发展趋势进行了展望。     

Biological and medical significance of calcium phosphates

The inorganic part of hard tissues (bones and teeth) of mammals consists of calcium phosphate, mainly of apatitic structure. Similarly, most undesired calcifications (i.e. those appearing as a result of various diseases) of mammals also contain calcium phosphate. For example, atherosclerosis results in blood-vessel blockage caused by a solid composite of cholesterol with calcium phosphate. Dental caries result in a replacement of less soluble and hard apatite by more soluble and softer calcium hydrogenphosphates. Osteoporosis is a demineralization of bone. Therefore, from a chemical point of view, processes of normal (bone and teeth formation and growth) and pathological (atherosclerosis and dental calculus) calcifications are just an in vivo crystallization of calcium phosphate. Similarly, dental caries and osteoporosis can be considered to be in vivo dissolution of calcium phosphates. On the other hand, because of the chemical similarity with biological calcified tissues, all calcium phosphates are remarkably biocompatible. This property is widely used in medicine for biomaterials that are either entirely made of or coated with calcium phosphate. For example, self-setting bone cements made of calcium phosphates are helpful in bone repair and titanium substitutes covered with a surface layer of calcium phosphates are used for hip-joint endoprostheses and tooth substitutes, to facilitate the growth of bone and thereby raise the mechanical stability. Calcium phosphates have a great biological and medical significance and in this review we give an overview of the current knowledge in this subject.     

Complicity of degradable polymers in health-care applications

Polymeric biomaterials have revolutionized biomedical technology and related fields as biomaterials for health-care applications. Recent trend in polymeric medical technology has adapted a tendency to substitute degradable polymers instead of non-degradable synthetic polymers for the advancement of various health-care modalities. They have got considerable attention for their potential in various interdisciplinary arenas, which implies tissue engineering scaffolds, sustainable drug release, delivery agents, regenerative medicine, and development of life-saving devices, implants, dental products as well as in food technology. Various types of degradable polymers are been developed to date having stringent features applicable for various aspects in modern science. Thus, being the most renovative field of biomedicine and biomedical technology degradable polymers has gained substantial acceptance and appreciation recent times. This review critically underlines various degradative polymers and their subtypes, potential applications, types of degradation, and their possible effects in the biological system. Assessment of possible toxicological risks behind is an important criterion to be focused before validating any biomaterial safe for biomedical applications. Therefore various toxicological assessment strategies and their impact in biomedicine and technology were also included. In addition, the risk versus benefit assessment is also critically summarized.     

Cycloolefin-Copolymer/Polyethylene (COC/PE) Blend Assists with the Creation of New Articular Cartilage

It is shown that the initial biomechanical stability of the applied COC/PE blend in the treated tissue locality, the initial integrity of biomaterials substituting the subchondral bone by polymer implant, the initial bearing capacity and the vertical position of these biomaterials have a mayor influence on the regeneration of new articular cartilage and subchondral bone. These aspects are essential for a prosperous treatment of osteochondral defects. Results reveal that the initial biomechanical stiffness of materials (substituting the subchondral bone) has a fundamental influence on both the quality and the quantity of new articular cartilage and subchondral bone. Research is also aimed at the application of suitable biologically tolerated polymer material, its surface modifications, verifications of the vertical position of implants in relation to the articular cartilage surface and ensuring the initial biomechanical stability of the polymer implant.     

Surface Modification Strategies to Improve the Osseointegration of Poly(etheretherketone) and Its Composites

In the last 5 years, a wide variety of surface modification strategies are explored to improve the integration of poly(etheretherketone) (PEEK) implants with bone. Since PEEK does not support bone on‐growth, its surface properties need to be tailored to promote osteogenesis at the bone‐implant interface. Surface modifications applied to achieve this response range from simple surface morphology changes to the deposition of osteoconductive coatings. Of the many methods, titanium and/or hydroxyapatite coatings, extrusion to create surface pores, and an accelerated neutral atom beam treatment have been approved by the U.S. Food and Drug Administration to improve the integration of PEEK spinal cages. The success of these surface modifications brings hope for the clinical translation of other techniques in the future, but there are several limitations that may be preventing other treatments from reaching the clinic. This review describes numerous strategies that have been applied to PEEK‐based implants for improving their osseointegration and enhancing their antibacterial properties. The review concludes with a discussion about future directions for the field and provides suggestions for advancing clinical translation of surface‐modified PEEK implants to improve the lives of patients in need of these implants.     

Bioactive Glasses—Structure and Properties

Bioactive glasses were the first synthetic materials to show bonding to bone, and they are successfully used for bone regeneration. They can degrade in the body at a rate matching that of bone formation, and through a combination of apatite crystallization on their surface and ion release they stimulate bone cell proliferation, which results in the formation of new bone. Despite their excellent properties and although they have been in clinical use for nearly thirty years, their current range of clinical applications is still small. Latest research focuses on developing new compositions to address clinical needs, including glasses for treating osteoporosis, with antibacterial properties, or for the sintering of scaffolds with improved mechanical stability. This Review discusses how the glass structure controls the properties, and shows how a structure‐based design may pave the way towards new bioactive glass implants for bone regeneration.     

The Development of Bioglass Ceramics for Medical Applications

The enormous progress made in the field of medicine over the past few decades has been partly due to the introduction of new instruments but also a result of the use of new materials. It is impossible to imagine modern medicine without metals, alloys, sintered corundum, organic high polymers (also as composite materials), glassy carbon, etc. Bioglass ceramics open up new possibilities for medical treatment and constitute a new area of research in the natural sciences and medicine. Owing to their widely variable combinations of properties, bioglass ceramics can be more easily adapted to suit medical requirements than can customary implants. Two properties of bioglass ceramics are of primary importance: their biocompatibility, i.e., acceptance of the material by the tissues of the human body without irritation, rejection reactions, or toxic effects; and their bioactivity, i.e., the ability to establish firm intergrowths with tissues of the human body. This property is not shared by any of the classical biomaterials. A wide range of applications is envisaged for the bioglass ceramics that have so far been developed; some are still undergoing animal tests while others are being clinically tested in humans. Possible applications are the replacement of vertebrae and use in the middle ear, throat, nose, and eye, in the entire head region, in the shoulder and leg, and in dental prosthetics, in particular the replacement of dental roots (a hard tissue substitute in the broadest sense of the word). The question as to the behavior of a bone/bioglass ceramic contact or bond on a long-term scale and on being exposed to varying mechanical stress has still not been satisfactorily answered, because interdisciplinary research in this field is still immature. All observations made so far indicate, however, that the materials do not cause any adverse effects.     

Bone‐guided regeneration: from inert biomaterials to bioactive polymer (nano)composites

Natural bone is a unique nanostructured material made of collagen fibre matrix and hydroxyapatite (HA) nanocrystals, providing mechanical support and protection from the vertebrate skeleton. However, in severe cases like bone‐deficiencies, bone needs to be “externally” repaired. Initially, different biological solutions were developed in bone‐guided regeneration. However, due to the limitations with the existing biological grafts, a lot of researches have been devoted toward biomaterials including metals, ceramics, and polymers. On the basis of the interface reactions between the implant and the surrounding tissues, these biomaterials may be classified as “nearly inert” or bioactive. Interestingly, the bioactive materials exhibit a specific biological response, leading to the formation of a natural bonding junction between the bone and the implant during bone regeneration. Recently, a special attention has been paid to a new generation of bioactive materials, i.e. (nano)structured biomaterials composed of a bioresorbable polymer matrix reinforced with bioactive inorganic compounds. While (bio)ceramic component provides the bioactivity, these materials can be readily engineered in such a way that their resorption rate in the body match the formation rate of the new tissue. This review hence reports the different biological and non‐biological solutions developed in bone‐guided regeneration, with a special emphasis on polymer‐based materials, and our recent results obtained in osseointegration The bone physiology, and its natural regeneration are also described. Copyright © 2011 John Wiley & Sons, Ltd.