The Critical Role of Geometry of Porous Hydroxyapatite Delivery System in Induction of Bone by Osteogenin, a Bone Morphogenetic Protein

Ripamonti, Ugo; Ma, Shuhua; Reddi, A. Hari

doi:10.1016/s0934-8832(11)80063-6

Cited by 202 publications

(92 citation statements)

References 15 publications

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“…Synthetic materials that are potential candidates to serve as BMP carriers include ceramics, bioactive glasses, and polymers. Ceramics can be classified as non-resorbable, such as synthetic hydroxyapatite (127,128), or resorbable, such as b-tricalcium phosphate (122,129) and calcium sulphate (130). Bioactive glasses and glass-ceramics contain SiO 2 , Na 2 O, CaO and P 2 O 5 in specific proportions.…”

Section: Role Of Bmp Carriers In Bone Inductionmentioning

confidence: 99%

“…Geometrical parameters such as size and shape can influence the degradation rate of the carrier, the rate of release of BMP, and the bonding of bone to the implant. Some geometrical configurations, for example solid hydroxyapatite particles and solid polymer discs, have been found to be unfavourable for bone induction (165, 166); conversely, porous discs or blocks of hydroxyapatite were favourable for bone induction, and granules of hydroxyapatite with identical pore dimensions did not elicit bone formation (128,167). Pore size of hydroxyapatite was found to be optimal between 300-400 mm (168).…”

Section: Geometry Of the Carriermentioning

confidence: 99%

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Bone morphogenetic proteins in human bone regeneration

Groeneveld

Burgér

2000

European Journal of Endocrinology

358

217

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Recently, the first clinical reports on bone regeneration by two recombinant human bone morphogenetic proteins (rhBMPs), BMP-2 and BMP-7 (also named osteogenic protein-1, OP-1) have been published (1-4) . Although both BMPs were able to support bone regeneration, a significant variation in individual response was observed with both proteins. Animal studies and laboratory experiments reveal a number of conditions that influence the osteoinductivity of BMP, such as BMP concentration, carrier properties and influence of local and systemic growth factors and hormones. In this paper, these studies and the clinical reports are reviewed, and the conditions that modulate the BMP-dependent osteoinduction are discussed. The information may provide clues as to how the performance of recombinant human BMP as bone-graft substitute in humans can be improved. European Journal of Endocrinology 142 9-21 BMP and demineralized bone matrixThe history of bone morphogenetic proteins (BMPs) began with the observation that demineralized bone matrix (DBM) is able to induce ectopic bone formation in subcutaneous and intramuscular pockets in rodents (5, 6). This bone induction process has been studied extensively (7-13). Histological and biochemical analyses showed that cartilage appears 5-10 days after implantation of active DBM (8). This cartilage mineralizes by day 7-14 and is subsequently replaced by bone (7-9). After 21 days, haematopoietic bone marrow formation can be observed (12). These cellular events observed after DBM implantation mimic embryonic bone development and normal fracture repair (11). As DBM-related bone formation was observed to occur at ectopic sites, it was assumed that pluripotent mesenchymal cells are attracted to the site of implantation. Isolation of the bone-inducing substance revealed that certain proteins were responsible, which were termed bone morphogenetic proteins (BMPs) or osteogenetic proteins (OPs).The use of DBM in treating bone defects has proven beneficial for bone regeneration both in animals and in humans (14-17). DBM has become widely accepted as a bone-graft substitute in clinical practice (18-22), but its bone inductive capacity has been questioned (23, 24). In several studies, including our own, histology revealed that new bone was generated by osteoconduction rather than osteoinduction (25-27) -that is, bone regeneration occurred by growth of existing host bone on the DBM granules, which acted as a scaffold, rather than by de novo differentiation of bone, independent of pre-existing bone. Lack of inductive properties of DBM may be related to the procedures of production of commercially available DBM, as preservation of osteoinductive activity can be affected by the processing (28-30) or sterilization procedures (31). It is also possible that DBM of human origin, which is preferred for use in clinical practice, is less osteoinductive than DBM derived from animals, which is commonly used in animal studies. Several studies show that DBM from long-lived species such as baboon and human...

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Section: Role Of Bmp Carriers In Bone Inductionmentioning

confidence: 99%

Section: Geometry Of the Carriermentioning

confidence: 99%

Bone morphogenetic proteins in human bone regeneration

Groeneveld

Burgér

2000

European Journal of Endocrinology

358

217

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“…[7][8][9][10][11] Recently, our studies demonstrated that a small amount of recombinant human BMP-2 could promote the differentiation of rat MSCs into osteogenic lineages in a porous HA ceramic system or in a diffusion chamber system. The findings were confirmed by histological and biochemical findings.…”

Section: Introductionmentioning

confidence: 95%

Recombinant growth/differentiation factor‐5 (GDF‐5) stimulates osteogenic differentiation of marrow mesenchymal stem cells in porous hydroxyapatite ceramic

Shimaoka

Dohi

Ohgushi

et al. 2003

J Biomedical Materials Res

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Abstract:To evaluate the growth/differentiation factor-5 (GDF-5) in the in vivo osteogenic potential of bone marrow mesenchymal stem cells (MSCs), we subcutaneously implanted five different kinds of hydroxyapatite (HA) ceramic implants: HA alone, GDF-5/HA composites (GDF/HA), MSCs/HA composites, the MSCs/HA composites supplemented with GDF-5 (GDF/MSCs/HA), and recombinant bone morphogenetic protein-2 (BMP/MSCs/HA). Neither the HA alone nor the GDF/HA composites exhibited any bone formation at any time after implantation. At 4 weeks, the MSCs/HA composites exhibited a certain amount of bone formation in some pore areas. In contrast, at 2 weeks, the GDF/MSCs/HA composites exhibited histologically obvious de novo bone formation together with active osteoblasts in many pore areas and additional bone formation at 4 weeks. In the de novo formed bone, neither chondrocytes nor endochondral bone was detected. The GDF/MSCs/HA composites also showed high alkaline phosphatase (ALP) and osteocalcin expression determined at both the protein and gene levels and the high level of expression was well maintained even at 4 weeks. Compared with GDF/MSCs/ HA, the BMP/MSCs/HA composites exhibited excellent osteogenesis with relatively early osteoblastic phenotype expression. The results indicate that GDF-5 synergistically enhances de novo bone formation capability of MSCs/HA composite and suggest that tissue-engineered GDF/ MSCs/HA composites could be used as bone graft substitutes.

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“…In this study, we used covalent cross-linked alginic acid sheet for transplantation as a carrier. Now, hydroxyapatite 42) , calcium phosphate 43) , polylactic acid and polyglycolic acid [44][45][46][47] have been investigated as a carrier, and these carriers had been proven its efficacy. We regarded that the alginic acid sheet have weak ability to induce hard tissue formation by itself ( Fig.…”

Section: Discussionmentioning

confidence: 99%

The possibility of genistein as a new direct pulp capping agent

et al. 2013

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Genistein, kind of soy isoflavones, is well-known as natural ingredients and consumed as health foods and supplements. They are expected to improve renal function. They have high-affinity to estrogen receptor β expressed predominantly in bone tissue, they prevent osteoporosis specifically and safely. We examined whether genistein can be a new direct capping agent. In this study, we examined the effect of genistein for the proliferation and differentiation of rat dental pulp cells in vitro and the ability of tertiary dentin formation in vivo. As a result, rat dental pulp cells with genistein were increased activity of ALPase and showed alizarin red positive-staining. Calcification-related genes expression has been confirmed by the addition of genistein. From in vivo study, high quality of tertiary dentin formation and minor pulp reaction were observed. From these findings, it was suggested that genistein may be useful agent for direct pulp capping.

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The Critical Role of Geometry of Porous Hydroxyapatite Delivery System in Induction of Bone by Osteogenin, a Bone Morphogenetic Protein

Cited by 202 publications

References 15 publications

Bone morphogenetic proteins in human bone regeneration

Bone morphogenetic proteins in human bone regeneration

Recombinant growth/differentiation factor‐5 (GDF‐5) stimulates osteogenic differentiation of marrow mesenchymal stem cells in porous hydroxyapatite ceramic

The possibility of genistein as a new direct pulp capping agent

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