Biomedical subjects

E H Burger

Publications and source records attributed to E H Burger.

At least 37 records · Page 2Linked to original sources

PubMed2001

Osteopontin-deficient bone cells are defective in their ability to produce NO in response to pulsatile fluid flow.

Osteopontin (OPN) is a noncollagenous component of bone matrix. It mediates cell attachment and activates signal transduction pathways. In this work, bone cells, cultured from fragments of long bones derived from wild-type and OPN-/- ("knock-out") mice, were exposed to pulsatile fluid flow (PFF) over a 60-min period. The medium was assayed periodically for nitric oxide (NO) and prostaglandin E(2) (PGE(2)) release. OPN+/+ cells exhibited a peak of NO production 5-10 min after the onset of PFF, decreasing to a stable plateau at 15 min; much less NO was produced by the OPN-/- cells. PFF resulted in reduced PGE(2) release by both cell types, although the reduction was less for the OPN-/- cells in the 15-30 min window. Both cell types exhibited a similar enhancement of cyclooxygenase2 mRNA levels 60 min after initiation of PFF. These results suggest that bone cells require OPN to respond fully to PFF as assessed by increased NO and reduced PGE(2) synthesis.

Animals↗

PubMed2001

Different responsiveness of cells from adult and neonatal mouse bone to mechanical and biochemical challenge.

Neonatal rodent calvarial bone cell cultures are often used to study bone cell responsiveness to biochemical and mechanical signals. However, mechanical strains in the skull are low compared to the axial and appendicular skeleton, while neonatal, rapidly growing bone has a more immature cell composition than adult bone. In the present study, we tested the hypothesis that bone cell cultures from neonatal and adult mouse calvariae, as well as adult mouse long bones, respond similarly to treatment with mechanical stress or 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3). Treatment with pulsating fluid shear stress (0.6 +/- 0.3 Pa, 5 Hz) caused a rapid (within 5 min) 2-4-fold increase in NO production in all cases, without significant differences between the three cell preparations. However, basal NO release was significantly higher in neonatal calvarial cells than adult calvarial and long bone cells. The response to 1,25(OH)2 D3), measured as increased alkaline phosphatase activity, was about three times higher in the neonatal cells than the adult cell cultures. We conclude that all three types of primary bone cell cultures responded similarly to fluid shear stress, by rapid production of NO. However, the neonatal cell cultures were different in basal metabolism and vitamin D3 responsiveness, suggesting that cell cultures from adult bone are best used for in vitro studies on bone cell biology.

Alkaline Phosphatase↗

PubMed2001

The production of nitric oxide and prostaglandin E(2) by primary bone cells is shear stress dependent.

Loading-induced flow of interstitial fluid through the lacuno-canalicular network is a likely signal for bone cell adaptive responses. However, the nature of the stimulus that activates the cell is debated. Candidate stimuli include wall shear stress, streaming potentials, and chemotransport. We have addressed the nature of the flow-derived cell stimulus by comparing variations in fluid transport with variations in wall shear stress, using nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production as a parameter of bone cell activation. Adult mouse long bone cell cultures were treated for 15min with or without pulsating fluid flow using the following regimes: Low PFF, mean flow rate 0.20 cm(3)/s, 3 Hz, shear stress 0.4+/-0.12 Pa; Medium PFF, 0.33 cm(3)/s, 5 Hz, 0.6+/-0.27 Pa; and High PFF, 0.63 cm(3)/s, 9Hz, 1.2+/-0.37 Pa. In some Low PFF experiments, 2.8% neutral dextran (mol. wt. 4.98x10(4)) was added to the flow medium to increase the viscosity, thereby increasing the wall shear stress 3-fold to a level similar of the High PFF stimulus, but without affecting streaming potentials or chemotransport. NO and PGE(2) production were stimulated by Low, Medium, and High PFF in a dose-dependent manner. Application of Low PFF using dextran-supplemented medium, enhanced both the NO and PGE(2) response by 3-fold, to a level mimicking the response to High PFF at normal viscosity. These results show that the production of NO and PGE(2) by bone cells can be enhanced in a dose-dependent manner by fluid flow of increasing wall shear stress. Therefore, the stimulus leading to NO and PGE(2) production is the flow-derived shear stress, and not streaming potentials or chemotransport.

Animals↗

PubMed2001

Low-intensity ultrasound stimulates endochondral ossification in vitro.

Animal and clinical studies have shown an acceleration of bone healing by the application of low-intensity ultrasound. The objective of this study was to examine in vitro the influence of low-intensity ultrasound on endochondral ossification of 17-day-old fetal mouse metatarsal rudiments. Forty-six triplets of paired metatarsal rudiments were resected 'en block' and cultured for 7 days with and without low-intensity ultrasound stimulation (30 mw/cm2). At days 1, 3, 5, and 7, the total length of the metatarsal rudiments, as well as the length of the calcified diaphysis were measured. Histology of the tissue was performed to examine its vitality. The increase in length of the calcified diaphysis during 7 days of culture was significantly higher in the ultrasound-treated rudiments compared to the untreated controls (P = 0.006). The growth of the control diaphysis was 180 +/- 30 microm (mean +/- SEM), while the growth of the ultrasound-treated diaphysis was 530 +/- 120 microm. The total length of the metatarsal rudiments was not affected by ultrasound treatment. Histology revealed a healthy condition of both ultrasound-treated and control rudiments. In conclusion, low-intensity ultrasound treatment stimulated endochondral ossification of fetal mouse metatarsal rudiments. This might be due to stimulation of activity and/or differentiation of osteoblasts and hypertrophic chondrocytes. Our results support the hypothesis that low-intensity ultrasound activates ossification via a direct effect on osteoblasts and ossifying cartilage.

Animals↗

PubMed2001

Histology of human alveolar bone regeneration with a porous tricalcium phosphate. A report of two cases.

Porous beta-phase tricalcium phosphate particles (pTCP) (Cerasorb) were used in two patients to restore or augment alveolar bone prior to the placement of dental implants. In one patient, pTCP was used to fill a large alveolar defect in the posterior mandible after the removal of a residual cyst, and in another patient to augment the sinus floor. Biopsies were taken at the time of implant placement, 9.5 and 8 months after grafting, respectively, and processed for hard tissue histology. Goldner-stained histological sections showed considerable replacement of the bone substitute by bone and bone marrow. In the 9.5 months biopsy of the mandible, 34% of the biopsy consisted of mineralised bone tissue and 29% of remaining pTCP, while the biopsy at 8 months after sinus floor augmentation consisted of 20% mineralised bone and 44% remaining pTCP. Bone and osteoid were lying in close contact with the remaining pTCP and were also seen within the micropores of the grafted particles. Tartrate resistant-acid phosphatase (TRAP) multinuclear cells, presumably osteoclasts, were found surrounding, within and in close contact with the pTCP particles, suggesting active resorption of the bone substitute. Remodelling of immature woven bone into mature lamellar bone was also found. No histological signs of inflammation were detected. The limited data presented from these two cases suggest that this graft material, possibly by virtue of its porosity and chemical nature, may be a suitable bone substitute that can biodegrade and be replaced by new mineralising bone tissue.

Absorbable Implants↗

PubMed2001

Transforming growth factor-beta1 incorporated in calcium phosphate cement stimulates osteotransductivity in rat calvarial bone defects.

Bone regeneration of the alveolar crest around dental implants is an important factor in the success of implant use. Calcium phosphate cement can be used as a bone substitute and applied clinically as a paste to fill micro- and macroscopic bone defects. We have shown earlier that the intermixing of the recombinant human transforming growth factor-beta1 (rhTGF-beta1) in hardening calcium phosphate cement stimulated osteoblastic differentiation of rat primary bone cells in vitro. The aim of the present study was to examine whether the similar enrichment with rhTGF-beta1 affects the replacement of calcium phosphate cement by bone (osteotransduction) in calvarial critical size defects (csd) of adult rats. Two bone defects of 5 mm diameter were created bilaterally in each skull of 10 adult male rats. Both defects were filled with 53 mg of calcium phosphate cement without rhTGF-beta1 (control) at one side, and with 10 or 20 ng rhTGF-beta1 at the other side. After 8 weeks, defects with surrounding skull were analysed histologically and histomorphometrically. The addition of rhTGF-beta1 in the cement increased the amount of bone in rat skull defects. This finding coincidences with our in vitro observations, that intermixing of rhTGF-beta1 in calcium phosphate cement stimulates bone cell differentiation. Addition of rhTGF-beta1 stimulated bone formation as indicated by an increased bone volume of 50% and an increased bone/cement contact of 65%, in comparison to control defects with cement without rhTGF-beta1. In addition, rhTGF-beta1 reduced the remaining volume of cement, by 11% at 10 ng rhTGF-beta1, and by 20% at 20 ng rhTGF-beta1 in the cement. Defect closure was not affected. We conclude that the intermixing of rhTGF-beta1 in a fast-setting calcium phosphate cement stimulates bone growth and the osteotransduction of the cement. For bone regeneration procedures around endosseous implants, calcium phosphate cement with rhTGF-beta1 might be an appropriate combination for early osseointegration and implant use.

Animals↗

PubMed2001

Estrogen enhances mechanical stress-induced prostaglandin production by bone cells from elderly women.

Several studies indicate that estrogen may enhance the effects of mechanical loading on bone mineral density in elderly women. This stimulating effect of estrogen could be due to increased sensitivity of bone cells to mechanical stress in the presence of estrogen. The present study was performed to determine whether 17beta-estradiol (E2) enhances mechanical stress-induced prostaglandin production and cyclooxygenase (COX)-2 mRNA expression. We subjected bone cells from seven nonosteoporotic women between 56 and 75 yr of age for 1 h to pulsating fluid flow (PFF) in the presence or absence of 10(-11) M E2 and measured prostaglandin production and COX-1 and COX-2 mRNA expression. One hour of PFF stimulated prostaglandin (PGE2) production threefold, PGI2 production twofold, and COX-2, but not COX-1, mRNA expression 2.9-fold. Addition of E2 further enhanced PFF-stimulated PGE2 production by 1.9-fold but did not significantly affect PGI2 production or COX-2 or COX-1 mRNA expression. E2 by itself did not affect any of the parameters measured. These results suggest that estrogen modulates bone cell mechanosensitivity via the prostaglandin synthetic pathway independently of COX mRNA expression.

Aged↗

PubMed2000

Use of recombinant human osteogenic protein-1 for the repair of subchondral defects in articular cartilage in goats.

The objective of this pilot study was to examine in vivo the potential of recombinant human osteogenic protein-1 (rhOP-1, also called bone morphogenetic protein-7, BMP-7) for treatment of subchondral lesions by induction of new hyaline cartilage formation. Subchondral left knee defects in 17 mature goats were treated with fresh coagulated blood mixed with (1) rhOP-1 combined with collagen (OP-1 device, 400 microgram/mL); (2) rhOP-1 alone (OP-1 peptide, 200 microgram/mL); (3) OP-1 device with small particles of autologous ear perichondrium; (4) OP-1 peptide with small particles of autologous ear perichondrium; or (5) autologous ear perichondrium alone (controls). rhOP-1 was combined with either collagen (OP-1 device) or not (OP-1 peptide). The defects were closed with a periosteal flap. The formation of cartilage tissue was studied by histologic and biochemical evaluation at 1, 2, and 4 months after implantation. One and 2 months after implantation there were no obvious differences between control and rhOP-1-treated defects. Four months after implantation, only one out of three controls (without rhOP-1) showed beginning signs of cartilage formation while all four rhOP-1-treated defects were completely or partly filled with cartilage. A significant linear relationship was found between rhOP-1 concentration and the total amount of aggrecan in the defects. These results suggest that implantation of rhOP-1 promotes cartilage formation in subchondral defects in goats at 4 months after implantation. Therefore, rhOP-1 could be a novel factor for regeneration of cartilage in articular cartilage defects.

Animals↗

PubMed2000

Differential stimulation of prostaglandin G/H synthase-2 in osteocytes and other osteogenic cells by pulsating fluid flow.

Mechanical stress produces flow of fluid in the osteocytic lacunar-canalicular network, which is likely the physiological signal for the adaptive response of bone. We compared the induction of prostaglandin G/H synthase-2 (PGHS-2) by pulsating fluid flow (PFF) and serum in osteocytes, osteoblasts, and periosteal fibroblasts, isolated from 18-day-old fetal chicken calvariae. A serum-deprived mixed population of primarily osteocytes and osteoblasts responded to serum with a two- to threefold induction of PGHS-2 mRNA. Serum stimulated PGHS-2-derived PGE(2) release from osteoblasts and osteocytes but not from periosteal fibroblasts as NS-398, a PGHS-2 blocker, inhibited PGE(2) release from osteocytes and osteoblasts with 65%, but not that from periosteal fibroblasts. On the other hand PFF (0.7 Pa, 5 Hz) stimulated (3 fold) PGHS-2 mRNA only in OCY. The related PGE(2) response could be completely inhibited by NS-398. We conclude that osteocytes have a higher intrinsic sensitivity for loading-derived fluid flow than osteoblasts or periosteal fibroblasts.

Animals↗

PubMed2000

Transforming growth factor-beta1 incorporated during setting in calcium phosphate cement stimulates bone cell differentiation in vitro.

Growth stimulation of periimplant tissues by growth factors like transforming growth factor-beta1 (TGF-beta1) may increase the indication for and success of implant use. Calcium phosphate as a material for implants or for coating of implants is known for its good biologic interaction with bone. Therefore, calcium phosphate implants combined with TGF-beta1 might improve osseointegration. In this study we hypothesise that the addition of recombinant human TGF-beta1 (rhTGF-beta1) to calcium phosphate cement (CPC) affects the differentiation of bone cells growing on the cement layer. rhTGF-beta1 incorporated during setting in a CPC layer at 20 ng rhTGF-beta1/60 mg cement was found to be gradually released into tissue culturing medium leading to a 20% release after 24 h. Two cell populations were obtained from collagenase-treated fragments of adult rat long bones: preosteoblastic cells, which were released by the collagenase treatment, and osteoblastic cells, which grew from the collagenase-stripped bone fragments. Both cell populations were tested for their osteoblastic characteristic phenotype by measuring their alkaline phosphatase (ALP) activity after vitamin D treatment and cyclic AMP after parathyroid hormone stimulation. After preculture the cells were plated on a layer of CPC containing 0 (control), 10, or 20 ng rhTGF-beta1/60 mg CPC. Bone cell differentiation was analyzed after 10 days by measuring the ALP activity, as well as the protein content of the cell layer. Incorporation of rhTGF-beta1 in the CPC did not change the ALP activity in osteoblastic cells, but a significant (analyzed by multivariate analysis of variance) increase was observed in preosteoblastic cells. Incorporation of 10 ng of rhTGF-beta1 in 60 mg of CPC increased the ALP activity in preosteoblastic cells by threefold and 20 ng rhTGF-beta1/60 mg CPC increased it by fivefold. The total protein content was not affected by rhTGF-beta1 in either of the cell populations. We conclude that rhTGF-beta1 incorporated during setting in CPC stimulates the differentiation of preosteoblastic cells in vitro. These results provide a basis for further studies on the use of this combination as an implant material in vivo.

1-Methyl-3-isobutylxanthine↗

PubMed2000

Influence of muscular activity on local mineralization patterns in metatarsals of the embryonic mouse.

This study addressed the theory that local mechanical loading may influence the development of embryonic long bones. Embryonic mouse metatarsal rudiments were cultured as whole organs, and the geometry of the primary ossification center was compared with that of rudiments that had developed in utero. The mineralization front in vivo was found to be nearly straight, whereas in vitro it acquired a more convex shape due to a slower mineralization rate at the periphery of the mineralized cylinder. A poroelastic finite element analysis was performed to calculate the local distributions of distortional strain and fluid pressure at the mineralization front in the metatarsal during loading in vivo as a result of muscle contractions in the embryonic hindlimbs. The distribution of fluid pressure from the finite element analysis could not explain the difference in mineralization shape. The most likely candidate for the difference was the distortional strain, resulting from muscle contraction, which is absent in vitro, because its value at the periphery was significantly higher than in the center of the tissue. Without external loads, the mineralization process may be considered as pre-programmed, starting at the center of the tissue and resulting in a spherical mineralization front. Strain modulates the rate of the mineralization process in vivo, resulting in the straight mineralization front. These results confirm that disturbances in muscle development are likely to produce disturbed mineralization patterns, resulting in a disordered osteogenic process.

Animals↗

PubMed2000

Mechanical stress induces COX-2 mRNA expression in bone cells from elderly women.

Mechanical loading-induced fluid flow in the lacuno-canalicular network is a possible signal for bone cell adaptive responses. In an earlier study we found that pulsating fluid flow (PFF, 0.7+/-0.02 Pa, 5 Hz, 0.4 Pa/s) stimulates the production of prostaglandins by neonatal mouse calvarial cells. In addition, mRNA expression of the inducible form of cyclooxygenase (COX-2), but not the constitutive form (COX-1), the major enzymes in prostaglandin production, was increased by PFF. The present study was performed to determine whether human primary bone cells from the iliac crest, respond to mechanical stress in a similar way as neonatal mouse calvarial cells. We subjected bone cells originating from the iliac crest of nine elderly women, between 56 and 80 yr of age, for 1 h to PFF and measured prostaglandin production and COX-1 and COX-2 mRNA expression. One hour PFF treatment stimulated the release of PGE2 by 3.5 fold and PGI2 by 2.2 fold. PFF also increased the expression of COX-2 mRNA by 2.9 fold, but did not change COX-1 mRNA. No correlation was found between donor age and PFF effect, neither on prostaglandin production nor on COX-2 mRNA expression. This study shows that bone cells from the iliac crest of elderly women react to PFF treatment in a similar way as neonatal mouse calvarial cells, namely with increased production of prostaglandins and upregulation of COX-2 mRNA expression. These results suggest that human bone cells from the iliac crest and neonatal mouse calvarial cells share a similar mechanotransduction pathway.

Aged↗

PubMed2000

Histological observations on biopsies harvested following sinus floor elevation using a bioactive glass material of narrow size range.

We evaluated the bone augmenting capacity of bioactive glass particles, size range 300-355 microns (BG-particles), in human sinus floor elevations using histomorphometrical methods. A total of 10 patients underwent bilateral grafting, using a 1:1 mixture of autogenous bone particles (from iliac crest) and BG-particles at one side (experimental side), and bone particles only at the other side (control side, split mouth design). A total of 72 bone biopsies were taken at the time of fixture installation; that is, 3 patients at 4 months, 3 at 5 months and 3 at 6 months after grafting and 1 patient at 16 months (when she presented again). In each case 6 biopsies were taken, 3 left and 3 right. Histomorphometry showed that in grafts at control sides, trabecular bone was present after 4 months, comprising almost 41% of the tissue volume. This bone contained viable osteocytes and was of mature lamellar type and showed a mature histological appearance. Bone volume continued to increase slightly, to 42% at 5 months, 44% at 6 months and 45% at 16 months. The graft volume at experimental sides consisted at 4 months for 28% of woven and some lamellar bone, and increased to 35% at 5 months and 38% at 6 months, when mainly lamellar bone was found. At 16 months a lamellar bone volume of 45% was found. The BG-particles transformed and became excavated with time, starting at 4 months, and their centers gradually filled with bone tissue. All BG-particles had disappeared by resorption at 16 months after grafting and had been replaced by bone tissue. Parameters of bone turnover (% osteoid surface, % resorption surface, mineral apposition rate as measured by tetracycline labeling) indicated that bone remodeling was very active at both sides, during more than 6 months, despite the mature histological appearance of the bone tissue. From these histological observations, we conclude that a 1:1 mixture of autogenous bone/BG-particles seems a promising alternative to autogenous bone only, when low amounts of bone tissue are available for sinus augmentation.

Absorbable Implants↗

PubMed2000

Recombinant human bone morphogenetic protein-7 in maxillary sinus floor elevation surgery in 3 patients compared to autogenous bone grafts. A clinical pilot study.

BACKGROUND/AIMS: This pilot study was designed to determine the clinical bone formation ability of a human recombinant DNA bone morphogenetic protein-7, also referred to as Osteogenic Protein-1 [OP-1] combined with a collagen carrier, implanted in the maxillary sinus of 3 patients. The results were compared with a group of 3 patients treated with sinus floor elevation and autogenous bone grafts. METHODS: 6 consecutive patients, 4 female and 2 male, between 48 and 57 years of age were treated by means of sinus floor elevation for insufficient bone height in the posterior maxilla for implant surgery. 3 patients, 2 female and 1 male, were treated with OP-1 attached to a collagen device. In these patients, 4 maxillary sinus grafting procedures according to Tatum's method were carried out. 1 g of collagen carrier containing 2.5 mg rhOP-1 mixed with 3 ml of saline was placed between the bony floor and the elevated mucosal lining of the most caudal part of the maxillary sinus, in order to increase the vertical bone dimension to place dental implants of a sufficient length. The 3 other patients, also 2 female and 1 male, with a total of 5 sinus sites, were treated with sinus floor elevation and autogenous iliac crest bone grafts. After 6 months, during dental implant preparation, bone cores were taken for histology. Thus, clinical, radiological and histological results of the 2 groups of 3 patients were compared. RESULTS: 6 months after sinus grafting with OP-1, in 1 male, well-vascularized bone-like tissue of good quality was observed clinically. This could be confirmed by histology. In the second, female, patient no bone formation was observed at all. A cyst-like granular tissue mass, without purulent content, was removed. In the 3rd, female, patient, who received bilateral sinus grafts, some bone-like formation was seen, however it showed flexible tissue which led to the decision that at 6 months after the sinus grafting, the implant placement had to be postponed. In all 5 autogenous grafted sinuses a bone appearance similar to normal maxillary bone was observed clinically as well as histologically and dental implants could be placed six months after sinus floor elevation surgery. CONCLUSIONS: These findings indicate that the OP-1 device has the potential for initiating bone formation in the human maxillary sinus within 6 months after a sinus floor elevation operation. However, the various findings in these 3 patients indicate that the behaviour of the material is at this moment insufficiently predictable, in this indication area. Further investigation is indicated before OP-1 can be successfully used instead of the "gold standard" autogenous bone graft.

Biopsy↗

PubMed2000

Response of periodontal ligament fibroblasts and gingival fibroblasts to pulsating fluid flow: nitric oxide and prostaglandin E2 release and expression of tissue non-specific alkaline phosphatase activity.

The capacity of the periodontal ligament to alter its structure and mass in response to mechanical loading has long been recognized. However, the mechanism by which periodontal cells can detect physical forces and respond to them is largely unknown. Besides transmission of forces via cell-matrix or cell-cell interactions, the strain-derived flow of interstitial fluid through the periodontal ligament may mechanically activate the periodontal cells, as well as ensure transport of cell signaling molecules, nutrients and waste products. Mechanosensory cells, such as endothelial and bone cells, are reported to respond to a flow of fluid with stimulated prostaglandin E2 (PGE2) and nitric oxide production. Therefore, we examined the PGE2 and nitric oxide response of human periodontal ligament and gingival fibroblasts to pulsating fluid flow and assessed the expression of tissue non-specific alkaline phosphatase activity. Periodontal ligament and gingival fibroblasts were subjected to a pulsating fluid flow (0.7 +/- 0.02 Pa, 5 Hz) for 60 min. PGE2 and nitric oxide concentrations were determined in the conditioned medium after 5, 10, 30 and 60 min of flowing. After fluid flow the cells were cultured for another 60 min without mechanical stress. Periodontal ligament fibroblasts, but not gingival fibroblasts, responded to fluid flow with significantly elevated release of nitric oxide and decreased expression of tissue non-specific alkaline phosphatase activity. In both periodontal ligament and gingival fibroblasts, PGE2 production was significantly increased after 60 min of flowing. Periodontal ligament fibroblasts, but not gingival fibroblasts, produced significantly higher levels of PGE2 during the postflow culture period. We conclude that human periodontal ligament fibroblasts are more responsive to pulsating fluid flow than gingival fibroblasts. The similarity of the early nitric oxide and PGE2 responses to fluid flow in periodontal fibroblasts with bone cells and endothelial cells suggests that these three cell types possess a similar sensor system for fluid shear stress.

Adolescent↗

PubMed2000

Chondrogenic potential of in vitro multiplied rabbit perichondrium cells cultured in alginate beads in defined medium.

Perichondrium has a chondrogenic capacity and is therefore a candidate tissue for engineering of cartilage in vitro. Donor age and culture conditions probably influence chondrogenesis. The aim of this study was to compare the chondrogenic capacity of ear and nasal perichondrium from young and adult rabbits, using serum containing and serum-free culture conditions. This study demonstrates that more than 1 million cells can be generated out of 1 cm(2) of perichondrium tissue in 3-5 weeks of culture, irrespective of age. Culturing of these cells in alginate in medium with 2, 10, or 20% fetal calf serum did result in the production of small amounts of glycosaminoglycan, but no collagen type II was demonstrated. When serum was replaced however by insulin-like growth factor-1 (IGF-1) (10 ng/mL) plus transforming growth factor-beta2 (TGF-beta2) (10 ng/mL) an increased glycosaminoglycan production and induction of collagen type II was found, especially in cells isolated from perichondrium of the ear. Cells derived from perichondrium of young rabbits showed larger chondrogenic potential than cells from perichondrium of adult rabbits. Moreover, stimulation of both glycosaminoglycan synthesis and collagen type II production was about five times higher in cells isolated from the ear perichondrium of young rabbits than of adult rabbits. We conclude that young auricular perichondrium seems a useful source of cells for tissue engineering of cartilage when cultured in serum-free medium in combination with IG-F1 and TGF-beta2.

Alginates↗

PubMed2000

Is BMU-coupling a strain-regulated phenomenon? A finite element analysis.

Histologically, two types of bone reconstruction are distinguished: modeling and remodeling. Modeling changes the amount of bone and determines its geometrical form in relation to the prevailing mechanical loads and their resulting deformation (strain). Remodeling renews existing bone in a sequence of resorption and formation. However, in both processes the cells responsible for resorption and formation are the same: osteoclasts and osteoblasts. We studied if there is a relation between the activity of these cells and the deformation of the local bone tissue during remodeling. Two finite element models were built on a microscopic, supracellular level: (1) a secondary osteon in cortical bone and (2) a Howship's lacuna in a trabecula. Both models were loaded in the "natural," that is, longitudinal direction. Equivalent strains were determined as a measure for the deformation of the bone tissue. In the first model, the strain field around the osteon showed a region of decreased deformation in front of the tunnel, just where osteoclasts excavate cortical bone tissue. Behind the cutting cone, elevated strain levels appear in the tunnel wall at locations where osteoblasts are active. The second model showed that a local excavation of a loaded trabecula leads to higher strains at the bottom of the lacuna, where resorption is stopped and osteoblasts are recruited to refill the gap. However, in the direction of loading reduced strain levels appear, just where resorption continues to proceed along the trabecular surface. We conclude that at the tissue level, strain distributions occur during the remodeling process that show a relationship to the activity of osteoblasts and osteoclasts. This suggests that BMU coupling, that is, the subsequent activation of osteoclasts and osteoblasts during remodeling, is a strain-regulated phenomenon.

Animals↗

PubMed2000

Bone morphogenetic proteins in human bone regeneration.

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.

Animals↗