Zeeshan Sheikh

Dicalcium phosphate cements: Brushite and monetite

Dicalcium phosphate cements were developed two decades ago and ever since there has been a substantial growth in research into improving their properties in order to satisfy the requirements needed for several clinical applications. The present paper presents an overview of the rapidly expanding research field of the two main dicalcium phosphate bioceramics: brushite and monetite. This review begins with a summary of all the different formulae developed to prepare dicalcium phosphate cements, and their setting reaction, in order to set the scene for the key cement physical and chemical properties, such as compressive and tensile strength, cohesion, injectability and shelf-life. We address the issue of brushite conversion into either monetite or apatite. Moreover, we discuss the in vivo behavior of the cements, including their ability to promote bone formation, biodegradation and potential clinical applications in drug delivery, orthopedics, craniofacial surgery, cancer therapy and biosensors.

Biodegradable Materials for Bone Repair and Tissue Engineering Applications

This review discusses and summarizes the recent developments and advances in the use of biodegradable materials for bone repair purposes. The choice between using degradable and non-degradable devices for orthopedic and maxillofacial applications must be carefully weighed. Traditional biodegradable devices for osteosynthesis have been successful in low or mild load bearing applications. However, continuing research and recent developments in the field of material science has resulted in development of biomaterials with improved strength and mechanical properties. For this purpose, biodegradable materials, including polymers, ceramics and magnesium alloys have attracted much attention for osteologic repair and applications. The next generation of biodegradable materials would benefit from recent knowledge gained regarding cell material interactions, with better control of interfacing between the material and the surrounding bone tissue. The next generations of biodegradable materials for bone repair and regeneration applications require better control of interfacing between the material and the surrounding bone tissue. Also, the mechanical properties and degradation/resorption profiles of these materials require further improvement to broaden their use and achieve better clinical results.

Macrophages, Foreign Body Giant Cells and Their Response to Implantable Biomaterials

All biomaterials, when implanted in vivo, elicit cellular and tissue responses. These responses include the inflammatory and wound healing responses, foreign body reactions, and fibrous encapsulation of the implanted materials. Macrophages are myeloid immune cells that are tactically situated throughout the tissues, where they ingest and degrade dead cells and foreign materials in addition to orchestrating inflammatory processes. Macrophages and their fused morphologic variants, the multinucleated giant cells, which include the foreign body giant cells (FBGCs) are the dominant early responders to biomaterial implantation and remain at biomaterial-tissue interfaces for the lifetime of the device. An essential aspect of macrophage function in the body is to mediate degradation of bio-resorbable materials including bone through extracellular degradation and phagocytosis. Biomaterial surface properties play a crucial role in modulating the foreign body reaction in the first couple of weeks following implantation. The foreign body reaction may impact biocompatibility of implantation devices and may considerably impact short- and long-term success in tissue engineering and regenerative medicine, necessitating a clear understanding of the foreign body reaction to different implantation materials. The focus of this review article is on the interactions of macrophages and foreign body giant cells with biomaterial surfaces, and the physical, chemical and morphological characteristics of biomaterial surfaces that play a role in regulating the foreign body response. Events in the foreign body response include protein adsorption, adhesion of monocytes/macrophages, fusion to form FBGCs, and the consequent modification of the biomaterial surface. The effect of physico-chemical cues on macrophages is not well known and there is a complex interplay between biomaterial properties and those that result from interactions with the local environment. By having a better understanding of the role of macrophages in the tissue healing processes, especially in events that follow biomaterial implantation, we can design novel biomaterials-based tissue-engineered constructs that elicit a favorable immune response upon implantation and perform for their intended applications.

The effect of autoclaving on the physical and biological properties of dicalcium phosphate dihydrate bioceramics: brushite vs. monetite.

Dicalcium phosphate dihydrate (brushite) is an osteoconductive biomaterial with great potential as a bioresorbable cement for bone regeneration. Preset brushite cement can be dehydrated into dicalcium phosphate anhydrous (monetite) bioceramics by autoclaving. This heat treatment results in changes in the physical characteristics of the material, improving in vivo bioresorption. This property is a great advantage in bone regeneration; however, it is not known how autoclaving brushite preset cement might improve its capacity to regenerate bone. This study was designed to compare brushite bioceramics with monetite bioceramics in terms of physical characteristics in vitro, and in vivo performance upon bone implantation. In this study we observed that monetite bioceramics prepared by autoclaving preset brushite cements had higher porosity, interconnected porosity and specific surface area than their brushite precursors. In vitro cell culture experiments revealed that bone marrow cells expressed higher levels of osteogenic genes Runx2, Opn, and Alp when the cells were cultured on monetite ceramics rather than on brushite ones. In vivo experiments revealed that monetite bioceramics resorbed faster than brushite ones and were more infiltrated with newly formed bone. In summary, autoclaving preset brushite cements results in a material with improved properties for bone regeneration procedures.

Oral antimicrobial peptides: Types and role in the oral cavity

Antimicrobial peptides (AMPs) are a wide-ranging class of host-defense molecules that act early to contest against microbial invasion and challenge. These are small cationic peptides that play an important in the development of innate immunity. In the oral cavity, the AMPs are produced by the salivary glands and the oral epithelium and serve defensive purposes. The aim of this review was to discuss the types and functions of oral AMPs and their role in combating microorganisms and infections in the oral cavity.

Bone Replacement Materials and Techniques Used for Achieving Vertical Alveolar Bone Augmentation

Alveolar bone augmentation in vertical dimension remains the holy grail of periodontal tissue engineering. Successful dental implant placement for restoration of edentulous sites depends on the quality and quantity of alveolar bone available in all spatial dimensions. There are several surgical techniques used alone or in combination with natural or synthetic graft materials to achieve vertical alveolar bone augmentation. While continuously improving surgical techniques combined with the use of auto- or allografts provide the most predictable clinical outcomes, their success often depends on the status of recipient tissues. The morbidity associated with donor sites for auto-grafts makes these techniques less appealing to both patients and clinicians. New developments in material sciences offer a range of synthetic replacements for natural grafts to address the shortcoming of a second surgical site and relatively high resorption rates. This narrative review focuses on existing techniques, natural tissues and synthetic biomaterials commonly used to achieve vertical bone height gain in order to successfully restore edentulous ridges with implant-supported prostheses.

Mechanisms of in Vivo Degradation and Resorption of Calcium Phosphate Based Biomaterials

Calcium phosphate ceramic materials are extensively used for bone replacement and regeneration in orthopedic, dental, and maxillofacial surgical applications. In order for these biomaterials to work effectively it is imperative that they undergo the process of degradation and resorption in vivo. This allows for the space to be created for the new bone tissue to form and infiltrate within the implanted graft material. Several factors affect the biodegradation and resorption of calcium phosphate materials after implantation. Various cell types are involved in the degradation process by phagocytic mechanisms (monocytes/macrophages, fibroblasts, osteoblasts) or via an acidic mechanism to reduce the micro-environmental pH which results in demineralization of the cement matrix and resorption via osteoclasts. These cells exert their degradation effects directly or indirectly through the cytokine growth factor secretion and their sensitivity and response to these biomolecules. This article discusses the mechanisms of calcium phosphate material degradation in vivo.

In vitro degradation and in vivo resorption of dicalcium phosphate cement based grafts

There are two types of DCP: dihydrated (brushite) and anhydrous (monetite). After implantation, brushite converts to hydroxyapatite (HA) which resorbs very slowly. This conversion is not observed after implantation of monetite cements and result in a greater of resorption. The precise mechanisms of resorption and degradation however of these ceramics remain uncertain. This study was designed to investigate the effect of: porosity, surface area and hydration on in vitro degradation and in vivo resorption of DCP. Brushite and two types of monetite cement based grafts (produced by wet and dry thermal conversion) were aged in phosphate buffered saline (PBS) and bovine serum solutions in vitro and were implanted subcutaneously in rats. Here we show that for high relative porosity grafts (50-65%), solubility and surface area does not play a significant role towards in vitro mass loss with disintegration and fragmentation being the main factors dictating mass loss. For grafts having lower relative porosity (35-45%), solubility plays a more crucial role in mass loss during in vitro ageing and in vivo resorption. Also, serum inhibited dissolution and the formation of HA in brushite cements. However, when aged in PBS, brushite undergoes phase conversion to a mixture of octacalcium phosphate (OCP) and HA. This phase conversion was not observed for monetite upon ageing (in both serum and PBS) or in subcutaneous implantation. This study provides greater understanding of the degradation and resorption process of DCP based grafts, allowing us to prepare bone replacement materials with more predictable resorption profiles.

Natural graft tissues and synthetic biomaterials for periodontal and alveolar bone reconstructive applications: a review

Periodontal disease is categorized by the destruction of periodontal tissues. Over the years, there have been several clinical techniques and material options that been investigated for periodontal defect repair/regeneration. The development of improved biomaterials for periodontal tissue engineering has significantly improved the available treatment options and their clinical results. Bone replacement graft materials, barrier membranes, various growth factors and combination of these have been used. The available bone tissue replacement materials commonly used include autografts, allografts, xenografts and alloplasts. These graft materials mostly function as osteogenic, osteoinductive and/or osteoconductive scaffolds. Polymers (natural and synthetic) are more widely used as a barrier material in guided tissue regeneration (GTR) and guided bone regeneration (GBR) applications. They work on the principle of epithelial cell exclusion to allow periodontal ligament and alveolar bone cells to repopulate the defect before the normally faster epithelial cells. However, in an attempt to overcome complications related to the epithelial down-growth and/or collapse of the non-rigid barrier membrane and to maintain space, clinicians commonly use a combination of membranes with hard tissue grafts. This article aims to review various available natural tissues and biomaterial based bone replacement graft and membrane options used in periodontal regeneration applications.

Bone Regeneration Using Bone Morphogenetic Proteins and Various Biomaterial Carriers

Trauma and disease frequently result in fractures or critical sized bone defects and their management at times necessitates bone grafting. The process of bone healing or regeneration involves intricate network of molecules including bone morphogenetic proteins (BMPs). BMPs belong to a larger superfamily of proteins and are very promising and intensively studied for in the enhancement of bone healing. More than 20 types of BMPs have been identified but only a subset of BMPs can induce de novo bone formation. Many research groups have shown that BMPs can induce differentiation of mesenchymal stem cells and stem cells into osteogenic cells which are capable of producing bone. This review introduces BMPs and discusses current advances in preclinical and clinical application of utilizing various biomaterial carriers for local delivery of BMPs to enhance bone regeneration.