Doped Bioactive Glass Materials in Bone Regeneration

In the arena of orthopaedic surgery, autograft is considered to be the gold standard for correction of fracture repair or other bone pathologies. But, it has some limitations such as donor site morbidity and shortage of supply, which evolved the use of allograft that also has some disadvantages such as immunogenic response to the host, low osteogenicity as well as possibilities of disease transmission. Despite the benefits of autografts and allografts, the limitations of each have necessitated the pursuit of alternatives biomaterials that has the ability to initiate osteogenesis, and the graft should closely mimic the natural bone along with regeneration of fibroblasts. A variety of artificial materials such as demineralised bone matrix, coralline hydroxyapatite and calcium phosphate-based ceramics such as hydroxyapatite (HA), β-tricalcium phosphate (β-TCP) and bioactive glass have been used over the decades to fill bone defects almost without associated soft tissue development. Most of them were having only the properties of osteointegration and osteoconduction. Only bioactive glass possesses osteogenic property that stimulates proliferation and differentiation of osteoprogenitor cells and in some cases influencing the fibroblastic properties. But, this material has also some disadvantages such as short-term and low mechanical strength along with decreased fracture resistance; but, this was further minimised by ion doping that positively enhanced new bone formation. There are many metal ions such as magnesium (Mg), strontium (Sr), manganese (Mn), iron (Fe), zinc (Zn), silver (Ag) and some rare earths that have been doped successfully into bioactive glass to enhance their mechanical and biological properties. In some of the cases, mesoporous bioactive glass materials with or without such doping have also been employed (with homogeneous distribution of pores in the size ranging between 2 and 50 nm). These biomaterials can be served as scaffold for bone regeneration with adequate mechanical properties to restore bone defects and facilitate healing process by regeneration of soft tissues as well. This chapter encompasses the use of bioactive glass in bulk and mesoporous form with doped therapeutic ions, their role in bone tissue regeneration, use as delivery of growth factors as well as coating material for orthopaedic implants

Applications of Different Bioactive Glass and Glass-Ceramic Materials for Osteoconductivity and Osteoinductivity

Throughout the world, research has been carried out in development of new methods and materials involving multidisciplinary approach for effective bone tissue repair and regeneration. Amid various biomaterials, bioactive glass material has drawn considerable attention due to their superior biocompatibility, degradability, ion leaching phenomena and propagation of osteogenic cells. In this concise review, effort has been made to summarize different material combinations available as composition to elaborate their biological properties both in vitro and in vivo, reaction kinetics in simulated body fluid, effect of different constituents of bioactive glass and glassceramic compositions, porosity, etc and finally these materials' applications as bone graft substitutes and various clinical applications have been detailed. In this review an attempt has been made to sum up the recent advancement of different bioactive glass and composite materials for osteoconductivity and osteoinductivity in orthopaedic surgical challenges

Role of calcium phosphate and bioactive glass coating on in vivo bone healing of new Mg-Zn-Ca implant

Present investigation focuses on development and detailed characterization of a new Mg alloy sample (BM) with and without coating of hydroxyapatite (BMH) and bioactive glass (BMG) by air plasma spray method. After detailed mechano-physico-chemical characterization of powders and coated samples, electrochemical corrosion and SBF immersion tests were carried out. Detailed in vitro characterizations for cell viability were undertaken using MG-63 cell line followed by in vivo tests in rabbit model for studying bone healing up to 60 days. Starting current density increases from BM to BMH to BMG indicating highest resistance towards corrosion in case of BMG samples, however BMH also showed highest i(corr) value suggesting slowest rate of corrosion than BM and BMG samples. Dissolution of calcium ion in case of BMH and BMG control formation of apatite phases on surface. Ca2+ ions of coatings and from SBF solution underwent reduction reaction simultaneously with conversion of Mg to MgCl2 releasing OH- in the solution, which increases pH. Viability and propagation of human osteoblast-like cells was verified using confocal microscopy observations and from expression of bone specific genes. Alkaline phosphatase assay and ARS staining indicate cell proliferation and production of neo-osseous tissue matrix. In vivo, based on histology of heart, kidney and liver, and immune response of IL-2, IL-6 and TNF alpha, all the materials show no adverse effects in body system. The bone creation was observed to be more for BMH. Although both BMH and BMG show rays of possibilities in early new bone formation and tough bone-implant bonding at interface as compared to bare Mg alloy, however, BMG showed better well-sprayed coating covering on substrate and resistance against corrosion prior implanting in vivo. Also, better apatite formation on this sample makes it more favourable implant. GRAPHICS]

Efficacy of nano-hydroxyapatite prepared by an aqueous solution combustion technique in healing bone defects of goat

The present study was undertaken to evaluate porous hydroxyapatite (HAp), the powder of which was prepared by a novel aqueous solution combustion technique, as a bone substitute in healing bone defects in vivo, as assessed by radiologic and histopathologic methods, oxytetracycline labeling, and angiogenic features in Bengal goat. Bone defects were created in the diaphysis of the radius and either not filled (group I) or filled with a HAp strut (group II). The radiologic study in group II showed the presence of unabsorbed implants which acted as a scaffold for new bone growth across the defect, and the quality of healing of the bone defect was almost indistinguishable from the control group, in which the defect was more or less similar, although the newly formed bony tissue was more organized when HAp was used. Histologic methods showed complete normal ossification with development of Haversian canals and well-defined osteoblasts at the periphery in group II, whereas the control group had moderate fibro-collagenization and an adequate amount of marrow material, fat cells, and blood vessels. An oxytetracycline labeling study showed moderate activity of new bone formation with crossing-over of new bone trabeculae along with the presence of resorption cavities in group II, whereas in the control group, the process of new bone formation was active from both ends and the defect site appeared as a homogenous non-fluoroscent area. Angiograms of the animals in the control group showed uniform angiogenesis in the defect site with establishment of trans-transplant angiogenesis, whereas in group II there was complete trans-transplant shunting of blood vessel communication. Porous HAp ceramic prepared by an aqueous combustion technique promoted bone formation over the defect, confirming their biologic osteoconductive property

Protein growth factors loaded highly porous chitosan scaffold: A comparison of bone healing properties

Present study aimed to investigate and compare effectiveness of porous chitosan alone and in combination with insulin like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) in bone healing. Highly porous (85 +/- 2%) with wide distribution of macroporous (70-900 mu m) chitosan scaffolds were fabricated as bone substitutes by employing a simple liquid hardening method using 2% (w/v) chitosan suspension. IGF-1 and BMP-2 were infiltrated using vacuum infiltration with freeze drying method. Adsorption efficiency was found to be 87 +/- 2 and 90 +/- 2% for BMP-2 and IGF-1 respectively. After thorough material characterization (pore details, FUR and SEM), samples were used for subsequent in vivo animal trial. Eighteen rabbit models were used to evaluate and compare control (chitosan) (group A), chitosan with IGF-1 (group B) and chitosan with BMP-2 (group C) in the repair of critical size bone defect in tibia. Radiologically, there was evidence of radiodensity in defect area from 60th day (initiated on 30th day) in groups B and C as compared to group A and attaining nearly bony density in most of the part at day 90. Histological results depicted well developed osteoblastic proliferation around haversian canal along with proliferating fibroblast, vascularization and reticular network which was more pronounced in group B followed by groups C and A. Fluorochrome labeling and SEM studies in all groups showed similar outcome. Hence, porous chitosan alone and in combination with growth factors (GFs) can be successfully used for bone defect healing with slight advantage of IGF-1 in chitosan samples. (C) 2012 Elsevier B.V. All rights reserved

MG63 osteoblast cell response on Zn doped hydroxyapatite (HAp) with various surface features

The clinical success of implant is governed by implant-surface and bone cell interaction that promote osseointegration and long term stability. Calcium hydroxyapatite (HAp) is a widely used bioceramic material for orthopedic and dental applications, which promotes bone tissue generation. Doped hydroxyapatite using various metallic ions is often reported to enhance this osteoconductive property. The objective of this study was to synthesize zinc doped HAp, to investigate the osteoblast cell response on this doped HAp and find out separately the effect of doping and different surface parameters on cell response. Slip casting technique was used to prepare pure and doped HAp specimens which were sintered at 1100 degrees C and 1250 degrees C. Different porosities, pore sizes were generated along with different surface roughness so as to understand the effect of these extrinsic parameters on cell culture. MG63 osteoblast cells were used for a maximum period of two weeks. Metabolic activity, adhesion and proliferation rate study of osteoblast cells on doped HAp showed significantly better response than pure HAp. Effect of doping was found to be more prominent than the effect of surface roughness

Animal trial on zinc doped hydroxyapatite: A case study

Calcium hydroxyapatite (HAp) has widely been used as bone substitute due to its good biocompatibility and bioactivity. In the present work, hydroxyapatite was doped with zinc (Zn) to improve its bioactivity. The study reports the technique to synthesize Zn-doped HAp powder using a simple, economic route and the influence of this dopant on the physical, mechanical and biological properties of the HAp. Porous blocks were prepared by sintering at 1150 °C and the sintered samples were characterized using XRD and FTIR. In vitro bioresorption behavior of the sintered blocks was assessed in simulated body fluid (SBF) maintained in a dynamic state. The in vivo study was exclusively conducted to evaluate healing of surgically created defects on the tibia of adult New Zealand rabbit after implantation of HAp. Local inflammatory reaction and healing of wound, radiological investigations, histological and SEM studies, oxytetracycline labeling and mechanical push-out test were performed up to 60 days post-operatively. It was observed that Zn substituted HAp showed better osteointegration than undoped HAp. Radiology revealed progressively less contrast between implant and surrounding bone. New bone formation in Zn-doped HAp was more prompt. Mechanical push-out test showed high interfacial strength (nearly 2.5 times) between host bone and doped implant

Systematic approach to treat chronic osteomyelitis through localized drug delivery system: Bench to bed side

Chronic osteomyelitis is a challenging setback to the orthopedic surgeons in deciding an optimal therapeutic strategy. Conversely, patients feel frustrated of the therapeutic outcomes and development of adverse drug effects, if any. Present investigation deals with extensive approach incorporating in vivo animal experimentation and human application to treat chronic osteomyelitis, using antibiotic loaded porous hydroxyapatite scaffolds. Micro- to macro-porous hydroxyapatite scaffolds impregnated with antibiotic ceftriaxone-sulbactam sodium (CFS) were fabricated and subsequently evaluated by in vivo animal model after developing osteomyelitis in rabbit tibia. Finally 10 nos. of human osteomyelitis patients involving long bone and mandible were studied for histopathology, radiology, pus culture, 3D CT etc. up to 8-18 months post-operatively. It was established up to animal trial stage that 50N50H samples [with 50-55% porosity, average pore size 110 mu m, higher interconnectivity (10-100 mu m), and moderately high drug adsorption efficiency (50%)] showed efficient drug release up to 42 days than parenteral group based on infection eradication and new bone formation. In vivo human bone showed gradual evidence of new bone formation and fracture union with organized callus without recurrence of infection even after 8 months. This may be a new, alternative, cost effective and ideal therapeutic strategy for chronic osteomyelitis treatment in human patients. (C) 2013 Elsevier B.V. All rights reserved