Biomedical subjects

C Rolfe Howlett

Publications and source records attributed to C Rolfe Howlett.

7 recordsLinked to original sources

PubMed2004

Effect of silicon doping on bone formation within alumina porous domains.

The effect of doping a porous bioinert bioceramic with silicon (Si) on tissue ingrowth, differentiation, and osteogenesis was studied using a rat intramedullary model. Alumina tubes (1.3-mm outer diameter, 0.6-mm inner diameter, 15-mm length) doped with Si at nominal concentrations of 0.5 and 5.0 mol % were implanted into femoral medullary canals of female rats for 16 weeks. Tissue formation within the tubes was determined by histology and histomorphometry. Addition of 0.5 mol % Si to alumina stimulated cellular activity at the bone-ceramic interface and impaired osteogenic maturation within the tubes. In contrast, osteogenesis was enhanced in the 5.0 mol % Si-doped alumina tubes. It is considered that effect of Si is related to surface chemistry rather than microstructure. This work demonstrates that doping a bioinert ceramic with small amounts of Si can significantly alter tissue ingrowth, differentiation, and osteogenesis within a porous implant.

Aluminum Oxide↗

PubMed2004

Use of an intramedullary in vivo model to study bone formation and maintenance in ceramic porous domains.

Tissue ingrowth, differentiation, and osteogenesis in a porous bioinert bioceramic were studied using an intramedullary model. Pure alumina tubes (1.3 mm outer diameter, 0.6 mm inner diameter, 15 mm length) were implanted in the femoral medullary canal of young female rats for 4, 6, 8, 12, and 16 weeks. Tissues present within each tube were characterized by histology and quantified by histomorphometry. A tissue front consisting of undifferentiated mesenchymal cells, fibrovascular tissue, osteoid, woven bone, and marrow penetrated the tube from both ends. Behind the front, woven bone remodeled to produce a thin layer of lamellar bone that lined the tube walls the entire distance to the tube ends and enclosed a marrow-filled lumen. The front was considered to represent the differentiation cascade from mesenchymal cells to fibrovascular tissue to osteoid to woven bone and marrow to lamellar bone and marrow. The fronts advanced into the tube with time such that, by 16 weeks, they were close to meeting or had met. In several instances, the tube was completely lined with a thin layer of mature lamellar bone continuous between the two ends and enclosing marrow. This configuration was considered to be the final equilibrium of tissues within the tube.

Aluminum Oxide↗

PubMed2004

Collagen-hydroxyapatite composite prepared by biomimetic process.

A novel bone graft substitute comprising a porous, collagenous scaffold was biomimetically coated with hydroxyapatite using a simulated body fluid solution chemistry method. The scaffold had a porosity of approximately 85%, with pore sizes between 30 microm and 100 microm. Glutaraldehyde vapor was used to stabilize the collagenous scaffold, giving a significantly increased thermal stability over an unstabilized scaffold, as shown by differential scanning calorimetry. A thin layer (<10 microm) of crystalline hydroxyapatite was deposited onto the stabilized collagenous scaffold by soaking the collagenous construct in simulated body fluid in the presence of calcium silicate glass. The presence of crystalline hydroxyapatite was confirmed by X-ray diffraction, energy-dispersive X-ray spectroscopy, and scanning electron microscopy. In vitro cytotoxicity testing of the composite construct using L-929 fibroblasts (ISO 10993-5) and rabbit periosteal cells revealed a cytocompatible material that supported cellular attachment and proliferation.

Animals↗

PubMed2004

Phenotypic expression of bone-related genes in osteoblasts grown on calcium phosphate ceramics with different phase compositions.

Calcium phosphate ceramics with different hydroxyapatite (HA) and tricalcium phosphate (TCP) ratios have different chemical properties. Does the difference in phase composition affect osteoblast behavior? In this study, osteoblasts were cultured on 4 kinds of calcium phosphate ceramics, i.e. pure (HA), HT1 (HA/TCP, 70/30), HT2 (HA/TCP, 35/65), and pure TCP. Cell proliferation of SaOS-2 cells together with bone-related genes' mRNA expression and protein production in osteoblasts cultured on different calcium phosphate ceramics were detected at different time points. Data suggested that cell proliferation rate on TCP ceramics was lower than that on the other substrates tested. Generally, mRNA expressions for osteonectin and osteocalcin were similar among the four kinds of ceramics in most circumstances, whereas at six days, alkaline phosphatase mRNA expression was higher on HA and HT1 surfaces than on the other two materials. Collagen I mRNA expression was also affected by the phase composition of substrates. Osteocalcin and bone sialoprotein production in SaOS-2 cells was very similar no matter which ceramic surface the cells were grown upon. This study revealed that calcium phosphate ceramics substrate could support osteoblast growth and bone-related gene expression and its gene expression pattern explained the basis of the biocompatibility and bioactivity for calcium phosphate ceramics.

Animals↗

PubMed2004

Proliferation and bone-related gene expression of osteoblasts grown on hydroxyapatite ceramics sintered at different temperature.

Human osteoblast-like cells SaOS-2 (ATCC HTB85) were seeded onto three kinds of hydroxyapatite (HA) ceramics sintered at different temperature (1200 degrees C, 1000 degrees C and 800 degrees C). Scanning electron microscopy (SEM) was conducted to detect the surface microstructure. Cells were cultured on these substrates for 6 and 12 days and cell proliferation rate and mRNA expression for osteocalcin, osteonectin, type I collagen and alkaline phosphatase and protein production for osteocalcin, bone sialoprotein and osteonectin were detected with quantitative in situ hybridization and immunocytochemistry techniques. SEM revealed that crystal particle size was affected by sintering temperature. Result showed that cell proliferation rate on HA ceramics sintered at 1200 degrees C was the highest. Osteonectin and type I collagen mRNA expression was not altered by sintering temperature. After 12 days in culture, bone sialoprotein, osteocalcin and osteonectin proteins levels were significantly (p<0.05) higher when SaOS-2 cells were cultured on HA sintered at 1200 degrees C, compared to the other two surfaces, suggesting that HA sintered at high temperature may be a better candidate for in vivo implantation. This result provides valuable information concerning the clinic application of HA ceramics sintered at different temperature.

Bone Substitutes↗

PubMed2004

Bone formation within alumina tubes: effect of calcium, manganese, and chromium dopants.

Alumina tubes (1.3mm outer diameter, 0.6mm inner diameter, 15 mm length) doped with Ca, Mn, or Cr at nominal concentrations of 0.5 and 5.0 mol% were implanted into femoral medullary canals of female rats for 16 weeks. Tissue formation within tubes was determined by histology and histomorphometry. Addition of Ca to alumina promoted hypertrophic bone formation at the advancing tissue fronts and tube entrances, and appeared to retard angiogenesis by limiting ongoing cellular migration into the tube. It is speculated that the presence of a secondary phase of calcium hexaluminate, probably having a solubility greater than that of alumina, possibly increased the level of extracellular Ca and, consequently, stimulated osteoclastic activity at the bone-ceramic interface. Addition of Mn significantly enhanced osteogenesis within the tubes. However, it is not possible to determine whether phase composition or microstructure of the ceramic was responsible for this because both were significantly altered by Mn addition. Addition of Cr to the alumina apparently stimulated bone remodelling as indicated by increased cellular activity and bone resorption at the tissue-implant interface. Cr was incorporated into the alumina as a solid solution and the tissue response was speculated to be an effect of surface chemistry rather than microstructure. The work demonstrates that doping a bioinert ceramic with small amounts of specific elements can significantly alter tissue ingrowth, differentiation, and osteogenesis within a porous implant.

Aluminum↗

PubMed2003

Reversible metaphyseal dysplasia, a novel bone phenotype, in two unrelated children with autoimmunepolyendocrinopathy-candidiasis-ectodermal dystrophy: clinical and molecular studies.

We report the association of an undescribed, reversible metaphyseal dysplasia (RMD) with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in two patients, one homozygous and one heterozygous for a 13-bp deletion in exon 8 of the autoimmune regulator (AIRE) gene. One patient also had a novel deletion in exon 6, resulting in a frameshift mutation and introduction of a STOP codon in exon 10. Their APECED phenotypes differed, but both patients developed progressive skeletal deformities and growth failure from early childhood. Radiological examination suggested a generalized abnormality of endochondral ossification, with irregular, flared, radioopaque regions in the metaphyses, subjacent to the growth plates. Histopathology in patient 1 showed islands of calcified cartilage within bone, consistent with impaired coupling of cartilage resorption with vascular invasion and ossification. Despite discordance for puberty, both patients experienced radiological resolution of their bone disease in their mid-teens, with improvement in histopathology in patient 1. RMD may constitute a rare phenotypic variation of APECED, possibly resulting from autoimmunity directed against skeletal proteins. We also demonstrated AIRE expression in chondrocytes derived from human fetal growth plates, primary culture of human chondrocytes, and two chondrosarcoma cell lines, suggesting a potential role for abnormal AIRE expression in the development of RMD.

Adult↗