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Biomedical subjects

J O Hollinger

Publications and source records attributed to J O Hollinger.

At least 19 recordsLinked to original sources
PubMed2003

Rabbit calvarial wound healing by means of seeded Caprotite scaffolds.

Autologous bone is the most successful bone-grafting material; however, limited supply and donor site morbidity are problematic. Synthetic bone substitutes are effective, but healing is slow and unpredictable. Osseous wound healing may be enhanced if bone substitutes are combined with autologous bone marrow cells. To test this hypothesis, we created 40 calvarial defects in 20 12-week-old New Zealand White rabbits, divided into four groups: (1) unrepaired controls, (2) autologous bone grafts, (3) unseeded Caprotite (a polymer-ceramic composite) grafts, and (4) Caprotite grafts seeded with autologous bone marrow stromal cells. CT scans were obtained at 0, 6, and 12 weeks post-operatively, and defects were harvested for histology. Defects repaired with autologous bone had significantly (p < 0.05) more bone than the other three groups, although seeded Caprotite defects showed different wound-healing sequelae. Results suggest that seeded Caprotite scaffolds did not significantly enhance osseous defect healing compared with controls.

Absorbable Implants↗
PubMed2001

Therapeutic potential of bone morphogenetic proteins.

Recently, there has been substantial progress in the area of bone morphogenetic protein (BMP) research. This review serves as an up-to-date summary of the history of BMPs, the mechanisms of BMP signalling and the role of BMPs in adipose, kidney, liver, bone and nervous system. The potential of BMPs as therapeutic agents will also be discussed.

Animals↗
PubMed2001

Controlled release from coated polymer microparticles embedded in tissue-engineered scaffolds.

The controlled release of proteins in tissue-engineered implants is being examined with the potential application to improve vascularization and hasten tissue growth. Bovine serum albumin (BSA), was encapsulated within poly(D,L-lactic-co-glycolic acid) [PLGA] microparticles. The microparticles were coated with poly(vinyl alcohol) and incorporated into PLGA tissue-engineered scaffolds during fabrication. The release of BSA from PLGA microparticles, coated PLGA microparticles, and microparticles embedded in a porous PLGA scaffold was measured. We have developed a novel approach that will permit incorporation of coated polymeric microparticles during PLGA scaffold fabrication. Growth factors or drugs could be incorporated into the microparticles resulting in a long-term, controlled release.

Animals↗
PubMed2000

Gene therapy approaches for modulating bone regeneration.

Following injury, bone has the ability to regenerate itself to a form and function nearly indistinguishable from the pre-injury state. However, if the injury is beyond a critical limit, recovery will not occur without therapeutic interventions. Autografts and implants with banked bone continue as the treatments of choice, although each exhibits limitations and liabilities. Alternatives have included the utilization of bone-graft substitutes that may incorporate bone derivatives and soluble signaling molecules such as mitogens and morphogens. In addition, an evolving treatment modality, gene therapy, offers an exciting avenue for bone regeneration. This review presents some of the current concepts for developing a rational gene therapy approach in bone regeneration.

Animals↗
PubMed2000

An osteogenic cell culture system to evaluate the cytocompatibility of Osteoset, a calcium sulfate bone void filler.

The purpose of the study was to describe a convenient, reliable and quantitative in vitro assay system to assess the cytocompatibility of a calcium sulfate bone filler on two osteogenic cell lines and primary osteoblasts. The hypothesis was that the bone void filler, OsteoSet pellets, would not impact adversely on cell proliferation kinetics or osteogenic potential of selected cells. The hypothesis was tested by standard in vitro methodology of placing OsteoSet pellets either directly in contact with osteogenic cells, or by compartmentalizing within transwell - clear microporous membrane inserts. Data analyses were accomplished with appropriate post hoc statistics (p < or = 0.05). In the presence of the OsteoSet pellets, the cell lines exhibited a decrease in cell proliferation at days 4 and 7, independent of either cell type or tissue culture medium. A decrease in the alkaline phosphatase enzyme activity occurred in the osteogenic cell lines maintained for 9 and 16 days in the presence of the OsteoSet pellets. However, with the exception of the MC3T3E-1 line, no differences were observed with respect to calcium deposition (mineralization) by day 16. Intact human osteocalcin release data for the human-derived OPC1 line and the primary osteoblasts was inconclusive as the OsteoSet pellets may interact with the osteocalcin secreted into the tissue culture medium. The present studies describe a cell culture system to assess the cytocompatibility of bone-graft substitutes with osteogenic cells by compartmentalizing material from direct cell contact (in transwells), and additionally, by evaluating direct cell/biomaterial interactions.

Alkaline Phosphatase↗
PubMed2000

Nicotine administration in rabbits using Habitrol nicotine patches and nicotine nasal spray.

1. Several methods are used to provide predictable and effective nicotine to experimental animals in scientific studies. Due to the expense and technical challenges of these methods, we sought suitable alternatives. Consequently, the purpose of the present study was to develop a reliable experimental nicotine protocol in rabbits that included either Habitrol nicotine patches (Novartis Consumer Health Inc., Summit, NJ, USA) or nicotine nasal spray. 2. Administration of one of three doses of nicotine (2.5, 5, or 10 mg) was accomplished daily on 13 rabbits divided between either the patch or spray groups. Systemic nicotine and cotinine levels at 0 h, 15 min and 8 and 24 h were assayed. Data were analysed by a Fisher's protected least significant difference test at P = 0.05. 3. Rabbits treated with Habitrol patches exhibited consistent and predictable systemic nicotine levels. The nicotine nasal spray produced an immediate dose-dependent response with no measurable nicotine serum levels at 8 h. 4. For nicotine administration in rabbits, nicotine patches are easy to administer and provide a nicotine serum level between 5 and 25 ng/mL, which is consistent with the average daily level found in a patient who smokes cigarettes.

Administration, Cutaneous↗
PubMed2000

Options for tissue engineering to address challenges of the aging skeleton.

There will be more than 52 million Americans over the age of 65 by the year 2020 (U.S. Census Bureau). Regenerating form and function to bone defects in an elderly, osteoporotic population of this magnitude will be a daunting challenge. Tissue engineering options must be considered to answer this challenge. Options can include gene transfer technology, stem cell therapy, and recombinant signaling molecules. An additional component will be a carrier that localizes, protects, predictably releases cues and cells, as well as establishes an environment for restoring osseous form and function. The purposes of this article are to present an overview of the bone regenerating decrement affecting osteoporotic, elderly patients and to highlight some tissue engineering options that could offset this decrement.

Aged↗
PubMed2000

Histomorphometry of parietal bones versus age and race.

Surgeons are used to obtaining bone grafts of calvaria, which are abundant and available. The outer table of the parietal bone can be split, usually at the level of the diploic interstice, with an osteotome. Inadvertently violating the inner table and the dura leads some surgeons to avoid using the outer table in the elderly. Sullivan and Smith measured the thickness of the outer tables, diploe, and inner table of 37 cadavers (average age, 59 years) and found each layer to be well preserved distinctly. However, they suggested that calvaria become brittle in patients older than 50 years of age. The current authors hypothesized that diploic composition is not changed, even in the elderly. The thickest part of the parietal bone of 49 Koreans and 30 whites were acquired, and undecalcified slides were made. Via light microscopy, using the National Institutes of Health image, the following measurements were made: the thickness of the parietal bone (PT), outer table (OT), diploe (DT), and inner table (IT); trabecular bone volume percent (TBV); trabecular thickness (TT); and trabecular separation (TS). There was no significant difference in the thickness of the OT, DT, and IT of the PT, TBV, TT, and TS among different ages. The PTs of women were thicker than men's. The PTs of whites were significantly thicker than Koreans'. This study disclosed that the DT is not different among varying age groups and is not sclerosed in the persons older than 80 years, and the OT of these individuals is not brittle. Thus, surgeons do not need to hesitate when taking the OT of the PT in older patients. However, the selection of the site is attentive to PT. The thickest posteromedial part of the PT is favorable and safe as a donor.

Adolescent↗
PubMed2000

Interface between titanium miniplate/screw and human calvaria.

This study demonstrates interfacial changes of titanium miniplate/screw with normal calvaria and nonvascularized calvarial bone graft ensued from craniectomy in a 53-year-old female. In 18 months after operation, a right parietal bone containing an L-shaped miniplate with screws, 5 mm long and 2 mm in external diameter, was harvested, fixed, and embedded in methylmetacrylate. Fifteen micrometer thick sections were made by an EXAKT cutting-grinding system (Exakt Company, Hamburg, Germany), and reviewed under the bright field light microscope. The mean of the bone-contacting surface ratio (BCSR) in six screwed bone was 64.1%; 69.3% in normal bone, and 60.4% in grafted bone. The trabecular bone areas in 10 x 5 mm (50 mm2) rectangular area of diploe surrounding the screws was 43.02 mm2; 45.25 mm2 in normal calvaria; and 41.82 mm2 in grafted bone. The mean Ca/P peak-height ratio of the plated and screwed calvaria was 1.47 in a 9 mm wide zone around each screw; 1.37 in normal calvaria; and 1.51 in grafted calvaria. We concede that the effect of direct contact of titanium with screws onto the bone is as much as an osseous integration (osseointegration).

Bone Plates↗
PubMed1999

Tissue engineering of bone in the craniofacial complex.

Tissue engineered therapies to regenerate bone in the craniofacial complex will probably include combinations of BMP-like molecules, a BMP-responsive set of cells (both endogenous and exogenous), and packaging in a surgically convenient format. In this report we have described our work with OPCs, BMP, and polymer: components suitable for tissue engineering.

Animals↗
PubMed1999

Impact of nicotine on bone healing.

A limited number of experimental animal studies and in vitro data confirm that nicotine impairs bone healing, diminishes osteoblast function, causes autogenous bone graft morbidity, and decreases graft biomechanical properties. Therefore, our long-term goal is to develop an effective therapy to reverse the adverse impact of nicotine from tobacco products. However, before accomplishing this goal, we had to develop an animal model. Our hypotheses were nicotine administration preceding and following autogenous bone grafting adversely affected autograft incorporation and depressed donor site healing in a characterized animal wound model. Hypothesis testing was accomplished in bilateral, 4-mm diameter parietal bone defects prepared in 60 Long-Evans rats (male, 35-day-old). A 4-mm diameter disk of donor bone was removed from the left parietal bone and placed in the contralateral defect. The donor site served as a spontaneously healing bone wound. The rats were partitioned equally among three doses of nicotine administered orally in the drinking water (12.5, 25, and 50 mg/L). For each dose, the duration and sequence of nicotine treatment followed four courses, including no nicotine and designated combinations of nicotine administration and abatement prior to and following osseous surgery. Experimental sites were recovered on 14 and 28 days postsurgery, responses quantitated, and data analyzed by analysis of variance and post hoc statistics (p < or = 0.05). We developed a convenient and effective osseous model, and the results validated our hypothesis that nicotine negatively impacts on bone healing.

Animals↗
PubMed1999

Tissue-engineered bone biomimetic to regenerate calvarial critical-sized defects in athymic rats.

A tissue-engineered bone biomimetic device was developed to regenerate calvaria critical-sized defects (CSDs) in athymic rats. Well-documented evidence clearly confirms that left untreated, CSDs will not spontaneously regenerate bone. To accomplish regeneration, four candidate treatments were assessed: porous poly(D,L-lactide) and type I collagen (PLC), PLC and human osteoblast precursor cells (OPCs) at 2 x 10(5) (PLC/OPCs), PLC and 50 microg of recombinant human bone morphogenetic protein-2 (PLC/rhBMP-2), and PLC/OPCs/rhBMP-2 (the bone biomimetic device). The hypotheses for this study were PLC/OPCs/rhBMP-2 would promote more new bone formation in CSDs than the other treatments and the amount of bone formation would be time dependent. To test the hypotheses, outcomes from treatments were measured at 2 and 4 weeks postoperatively by radiomorphometry for percent radiopacity and by histomorphometry for square millimeters of new bone formation. Data were analyzed by analysis of variance and Fisher's protected least significant difference for multiple comparisons with p < or = 0.05. At 2 and 4 weeks, radiomorphometric data revealed PLC/rhBMP-2 and PLC/OPCs/rhBMP-2 promoted significantly more radiopacity than either PLC or PLC/OPCs. Histomorphometry data at 2 and 4 weeks indicated significantly more new bone formation for PLC/rhBMP-2, PLC/OPCs/rhBMP-2, and PLC/OPCs compared to PLC. By 4 weeks, PLC/OPCs/rhBMP-2 and PLC/rhBMP-2 had regenerated the CSDs with more new bone than the other treatments; the quantity of bone at 4 weeks for these treatments was greater than at 2 weeks.

Animals↗
PubMed1999

Bone morphogenetic proteins: an update on basic biology and clinical relevance.

The regeneration of bone is a remarkable, complex physiological process, and BMPs are a formidable clinical tool to promote its regeneration. By defining roles played by BMPs in developmental biology and bone regeneration, significant progress has been made to identify cell-signaling molecules and their regulators. For example, the regulators of BMPs that include noggin, chordin, cerberus, dan, and gremlin may be harnessed as therapies to offset calcification encountered after total hip arthroplasties. Furthermore, exploiting BMPs and Smads may generate new therapeutic options for bone repair. Another compelling clinical consideration is the trans-acting factor osteoblast-specific factor-2, which can promote osteoblast differentiation. Moreover, the affiliation of osteoblast-specific factor-2 with heritable disorders merits exploration. A recognized daunting challenge includes a carrier/delivery system for the powerful morphogenetic therapeutic tools, as well as osteoprogenitor cells and intracellular transduction and transcriptional factors. In addition, the long-term effects of administering superphysiological doses of rhBMPs to patients must be assessed systematically. A new generation carrier/delivery system may be the answer to offset dosing liabilities as well as to provide residence for exogenous, BMP-receptive osteoprogenitor cells (111,112). The areas highlighted in this review offer fertile territory for thought and research to develop rational clinical treatments to promote bone regeneration and to understand some of the biological roles of BMPs.

Animals↗
PubMed1999

Reconstruction of bone using calcium phosphate bone cements: a critical review.

The calcium phosphate cements (CPCs) are rapidly emerging as a new technology in craniofacial surgery and will soon impact many areas of orthopedic and maxillofacial reconstructive surgery as well. These materials are, in many ways, substantially different from the previously marketed dense, crystalline, hydroxyapatite (HA) ceramic materials of the 1980s. The CPCs are blends of amorphous and crystalline calcium phosphate compounds and set to produce HA. These materials 1) have x-ray diffraction spectra similar to the mineral phase of bone, 2) set endothermically at body temperature, 3) are capable of being injected into fractures or bone defects, 4) have compressive strengths equal to or greater than bone, 5) form chemical bonds to the host bone, and 6) may exhibit osteoconductive properties. This review provides an overall commentary on the different types of CPCs, emphasizing those materials currently on the market or soon to emerge in the marketplace.

Animals↗
PubMed1999

Carrier systems for bone morphogenetic proteins.

Bone deficits can regenerate inherently, although when the amount of bone loss exceeds a critical limit, pseudarthrosis and fibrosis occur. Therapeutic intervention either with an autograft or allogeneic bank bone are traditional options to promote regeneration to overcome critical limits. However, liabilities with traditional treatments have inspired investigators to develop alternatives, such as combinations of biomimetic scaffolds and osteogenic regulatory molecules. The class of osteogenic regulatory molecules known as the bone morphogenetic proteins has several members that stimulate bone regeneration. Therapeutic applications of bone morphogenetic proteins require a well characterized carrier system to ensure safe and effective presentation at the implant site. Several carrier systems have been used to evaluate the sustained release and implant retention of recombinant human bone morphogenetic protein-2. The carrier systems used in this study include type I collagen, poly(D,L-lactide), and deorganified bovine bone. Pharmacokinetics of recombinant human bone morphogenetic protein-2 released from these systems were characterized in the rat ectopic assay. Pharmacokinetics were influenced by the implant carrier. For example, sustained release occurred with the collagen sponge. The recombinant human bone morphogenetic protein-2 from deorganified bovine bone resulted in a burst release at the first collection interval, but thereafter, appeared to bind irreversibly to the morphogen. The poly (D,L-lactide) systems showed a dose dependent sustained release pattern. These results indicate the physicochemical characteristics of a carrier system for recombinant human bone morphogenetic protein-2 impact the release kinetics and may have a profound influence on clinical outcome.

Animals↗
PubMed1999

Establishing an immortalized human osteoprecursor cell line: OPC1.

The present studies evaluated the feasibility of establishing a conditionally immortalized osteoprecursor cell line derived from human fetal bone tissue. Primary cultures were transfected with a plasmid in which the Mx-1 promoter drives the expression of SV40 T-antigen when activated by human A/D interferon. Several neomycin (G418)-resistant colonies were characterized for cell growth and alkaline phosphatase (ALP) enzyme activity. The clone, designated OPC1 (osteoblastic precursor cell line 1), which exhibited the highest ALP enzyme activity at passage 10 (P10), was selected for additional osteogenic phenotypic characterization. Reverse transcription-polymerase chain reaction (RT-PCR) phenotyping revealed abundant mRNA for osteocalcin (OC), osteonectin (ON), osteopontin (OP), parathyroid hormone receptor (PTHr), ALP, and procollagen type I (ProI). In addition, the levels of quantitative RT-PCR product of ON, OP, PTHr, and ProI mRNAs exhibited a marked up-regulation when maintained in medium containing an osteogenic supplement (OS). The ability to stimulate osteogenic differentiation was characterized in postconfluent OPC1 cells maintained in tissue culture medium supplemented with recombinant human bone morphogenetic protein-2 (rhBMP-2) either with or without an OS. All treatment groups exhibited a striking up-regulation of ALP enzyme activity that coincided with ALP histochemical observations. Postconfluent cells also exhibited the ability to form mineralized nodules under all treatments (confirmed by von Kossa histochemical staining and calcium deposition). An enzyme immunosorbent assay (EIA) was utilized to measure intact human OC from the OPC1 line under the various treatments. Abundant OC was evident in the tissue culture medium indicating de novo sythesis and release from the OPC1 line under appropriate conditions. The clonal human-derived OPC1 line represents a homogeneous osteogenic cell line that not only has maintained a consistent bone phenotype from P10 to at least P30, but has also exhibited the capacity to generate programmed differentiation in the presence of low dose rhBMP-2 (10 ng/ml). Thus, the OPC1 line is a human-derived osteoprecursor that provides a sensitive in vitro cell culture system to evaluate bone development, cell/biomaterial interactions, and may be a useful screen for putative bone differentiating factors.

Alkaline Phosphatase↗