Biomedical subjects

Hidetomi Terai

Publications and source records attributed to Hidetomi Terai.

At least 19 recordsLinked to original sources

PubMed2006

Repair of long intercalated rib defects using porous beta-tricalcium phosphate cylinders containing recombinant human bone morphogenetic protein-2 in dogs.

A new method to repair rib defects with biomaterials containing recombinant human bone morphogenetic protein-2 (rhBMP-2) is presented in this report. We had reported previously the successful regeneration of bony rib defects by placing a short chain of small beta-tricalcium phosphate (beta-TCP) cylinders on the intact periosteum. The multi-cylinder implants were ineffective in promoting rib repair when the periosteum was absent. By adding rhBMP-2 to the beta-TCP cylinders, we were able to promote rib bone regeneration in the presence or absence of the periosteum. The osteogenic capacity of the rhBMP-2/beta-TCP composite implant and the time required to complete regeneration were evaluated in a canine model. An 8cm long section of rib bone, including the periosteum, was removed and replaced with a chain of the rhBMP-2/beta-TCP cylinders. At 6 weeks after implantation, the ribs were restored to their original configuration and mechanical strength. The multi-cylinder beta-TCP implants were degraded and replaced by new bone in 12 weeks. This new degradable bone-inducing implant material has significant clinical potential for rib repair.

Absorbable Implants↗

PubMed2006

Ectopic bone formation in mice associated with a lactic acid/dioxanone/ethylene glycol copolymer-tricalcium phosphate composite with added recombinant human bone morphogenetic protein-2.

A new putty-like material with bone-inducing capacity was made by combining a block copolymer of poly d,l-lactic acid with randomly inserted p-dioxanone and polyethylene glycol (PLA-DX-PEG) and beta-tricalcium phosphate (beta-TCP) powder with added recombinant human bone morphogenetic protein-2 (rhBMP-2). To optimize the material's efficacy for bone formation, we formulated the optimal composition ratio of the respective constituent that gives the greatest osteoinductive efficacy in a mouse model of ectopic bone formation. In this series of studies, we investigated the size of ectopic bone mass induced 3 and 6 weeks after implantation of the materials composed of 30 mg of PLA-DX-PEG with 2 microg of rhBMP-2 and 0, 15, 30, or 60 mg of beta-TCP powder. An additional experiment was designed to investigate how content ratios of beta-TCP powder in 30 mg-putty implants (0%, 16.7%, 33.3%, 50%, 66.7%, 83.3%, or 100%) for a fixed dose (5 microg) of the rhBMP-2 altered the size of the induced ossicle. The results from the first experiment indicated that the bone yields were linearly dependent on the amount of additional beta-TCP powder. In the second experiment, the largest ossicles induced by 5 microg of rhBMP-2 were obtained when the polymer/beta-TCP ratio was 1/2 in mice. The data provide important insights into the fabrication of implants that provide efficacious delivery of rhBMP-2. The new putty-like material may be valuable for repairing or regenerating bone in a clinical setting.

Absorbable Implants↗

PubMed2006

A biodegradable delivery system for antibiotics and recombinant human bone morphogenetic protein-2: A potential treatment for infected bone defects.

To produce an osteogenic and bacteriocidal biomaterial for the treatment of infected nonunions or bone defects, a synthetic degradable block copolymer of poly-D,L-lactic acid segments with randomly inserted p-dioxanone and polyethylene glycol (PLA-DX-PEG) segments was mixed with recombinant human BMP-2 (rhBMP-2) and antibiotics at high concentration. We then examined the in vitro elution profile of an antibiotic (teicoplanin) from the polymer, the effects of antibiotics on the bone-inducing capacity of rhBMP-2 or on ectopic new bone formation induced by the rhBMP, and the ability of the polymer to repair bone in a rat cranial defect model. Approximately 40% of teicoplanin was released within the first 24 h, with the remaining amount released steadily over 21 days with no loss of antibacterial activity. The polymer had disappeared by degradation in the phosphate buffered saline (pH 7.4) at the end of the incubation period. The in vivo performance of pellets with antibiotics and rhBMP-2 revealed no significant change in bone yield within the ossicles after 3 weeks. Also, antibiotics had no inhibitory effect on the ability of rhBMP2 to repair cranial defects. Indeed, when the defect was filled by a polymer disc loaded with rhBMP-2 with or without teicoplanin, the defect was repaired by new bone, and normal anatomy was restored within 6 weeks. In conclusion, the PLA/DX/PEG polymer appears to work as effectively for antibiotics as it does for rhBMP-2. Additionally, the biological activity of rhBMP-2 was retained irrespective of the presence of antibiotics.

Absorbable Implants↗

PubMed2006

Accelerated repair of a bone defect with a synthetic biodegradable bone-inducing implant.

BACKGROUND: Nothing has ever had osteoinductive capacity and degradability equivalent to that of autogenous bone, although many types of biomaterials have been developed. To address this issue, we constructed a new bone graft substitute with osteogenic potential and degradability by using porous beta-tricalcium phosphate (beta-TCP) granules, bone morphogenetic protein (BMP), and a synthetic block copolymer composed of poly-D: ,L: -lactic acid with randomly inserted p-dioxanone and polyethylene glycol (PLA-DX-PEG). In this experimental study, the bone-inducing capacity and degradation properties of the composite implant during the bone healing process were examined in vivo in a cortical and cancellous bone defect model in rabbits. METHODS: The advantages of this type of implant have been examined in a cortical bone defect model created in the distal femur of rabbits. The defects (6.5 x 5 mm) were filled with 30 mg of various implants: BMP-H [rhBMP-2, 0.0025% (w/w)], BMP-L [rhBMP-2, 0.000625% (w/w)], control A (beta-TCP alone), and control B (no implant). The distal femurs were harvested at scheduled intervals after surgery and examined for the evaluation of the bony repair of the defects by three-dimensional computed tomography and histology. RESULTS: The repair of both cortical and cancellous bone occurred predominantly in the BMP-H group, and only minor cortical bone repair and cancellous bone formation were noted in the BMP-L and control A groups. Most of the beta-TCP was resorbed in the BMP-H group at 6 weeks after surgery, whereas a significant amount of beta-TCP remained in the BMP-L and control A groups. CONCLUSIONS: beta-TCP granules coated with a BMP-retaining synthetic polymer appear to be effective in enhancing the repair of both cancellous and cortical bone defects. The early disappearance of the implanted beta-TCP and restoration of the normal anatomy of bone tissue are two notable features of this approach.

Absorbable Implants↗

PubMed2006

Endoscopic vertebroplasty for the treatment of chronic vertebral compression fracture. Technical note.

The authors describe a new vertebroplasty technique for the treatment of chronic painful vertebral compression fractures (VCFs). A urinary balloon catheter is introduced into the vertebral body (VB) via a bilateral transpedicular approach and inflated with contrast medium to obtain sufficient space for endoscopic observation. The granulation tissue occupying the VB is then removed using a punch or curette inserted through one pedicle, with the guidance of an endoscope introduced through the contralateral pedicle. After endoscopic resection of granulation tissue in the fractured VB, vertebroplasty is performed by injecting calcium phosphate cement (CPC) into the VB. Fourteen patients in whom chronic painful VCFs were diagnosed underwent surgery involving the aforementioned technique. In all cases, intractable pain and ambulatory function improved after surgery, and there were no significant systemic complications. On radiological evaluation in eight cases in which the follow-up period exceeded 1 year, the mean height of the fractured VB improved from 38% of that of adjacent intact VBs to 85%. Although a slight loss of correction was routinely observed at 1 month postoperatively, an additional loss of VB height was not noted up to 1 year later. Bone formation was commonly seen along the anterior wall of the involved vertebrae in all cases. Vertebroplasty involving the endoscopic removal of granulation tissue proved to be an efficacious procedure for the treatment of chronic painful VCFs. The osteoconductive capacity of CPC facilitated callus formation and ultimately restoration of vertebral bone structure.

Aged↗

PubMed2006

[Application of bone morphogenetic protein (BMP) in regenerative medicine of bone].

Main purpose of bone morphogenetic protein (BMP) related research in clinical setting is the development of new efficient technologies to regenerate bone tissue effectively by utilizing BMP's osteoinductivity. Problems to be solved for that purpose are the development of efficient career system for BMP and the exploitation of methods to promote efficacy of BMP's bone forming activity. These new technologies will enable orthopaedic surgeons to replace currently used autografts with BMP combined implants. Additionally, they are also applicable for the acceleration of bone healing, treatment of non-union, spinal fusion, reconstruction of bone defects after the resection of bone tumor or arthroplasty. Thus, these new technologies are expected for the breakthrough in clinical applications of BMP.

Bone Morphogenetic Proteins↗

PubMed2006

[Experimental spinal fusion in a rabbit model with new drug delivery system for BMP].

Bone morphogenic protein (BMP) is a powerful bone-inducing cytokine and has been used as a new bone graft substitute with bovine-derived collagen sponge as a delivery system. Excellent clinical results have been reported with use of these BMP-retaining implants. However, certain problems remain with use of them, such as the need for high doses of BMP to obtain new bone formation, resulting in high cost, and the potential risks for disease transmission (e.g., variant Creutzfeldt-Jacob disease). To avoid use of collagen, we have developed a synthetic polymer/beta-Tricalcium Phosphate composite as a new delivery system for BMP. This new material, when used in combination with low doses of BMP-2, consistently elicited new bone and was successfully used to achieve posterolateral spinal fusion in a rabbit model.

Animals↗

PubMed2005

Optimized use of a biodegradable polymer as a carrier material for the local delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2).

To improve the efficacy of a block copolymer of poly-d, l-lactic acid with randomly inserted p-dioxanone and polyethylene glycol (PLA-DX-PEG) as a drug delivery system for recombinant human bone morphogenetic proteins (rhBMPs), we examined the relationship between the volume of PLA-DX-PEG, the dose of rhBMP-2 and osteoinduction in a mouse model of ectopic bone formation. In a series of studies, we compared the size and bone mineral content (BMC) of ectopically induced bone by PLA-DX-PEG and collagen sponges carrying different quantities of rhBMP (0, 1, 2, 5, 10, 20 microg). An additional experiment was designed to investigate how a range of PLA-DX-PEG polymer volumes (15, 30, 60, 90 mg) with a fixed rhBMP concentration (0.01 wt%), altered the size and BMC of the induced ossicle. The influence of polymer volume was also examined in a further experiment wherein a fixed amount of rhBMP was placed in a range of PLA-DX-PEG copolymer volumes to give different concentrations of the protein per implant (0.02-0.0017 wt%). The results indicate that the bone yields were linearly dependent on the dose of rhBMP and also were proportional to the polymer volume above the minimal concentration of rhBMP-2 (0.0017 wt% in this series). The optimal concentration of rhBMP-2 in PLA-DX-PEG was 0.003 wt% in mice. The data provide important insights into the fabrication of implants that provide efficacious delivery of rhBMP-2 using the lowest possible dose of this expensive osteoinductive protein. This information will be of value for the clinical use of BMPs.

Animals↗

PubMed2005

Experimental spinal fusion with recombinant human bone morphogenetic protein-2 delivered by a synthetic polymer and beta-tricalcium phosphate in a rabbit model.

STUDY DESIGN: An experimental animal study to achieve posterolateral intertransverse process spine fusion with recombinant bone morphogenetic protein in combination with a new delivery system. OBJECTIVE: To evaluate the efficacy of a new synthetic biodegradable bone-inducing material containing recombinant human bone morphogenetic protein-2 (rhBMP-2) as a bone-graft substitute for posterolateral intertransverse process fusion in a rabbit model. SUMMARY OF BACKGROUND DATA: rhBMP-2, a powerful bone-inducing cytokine, has been used as a bone graft substitute in combination with animal-derived collagen to achieve spinal fusion in animal models. However, the minimum dose of rhBMP-2 required to obtain solid posterolateral intertransverse process fusion was high on the basis of previous reports (>100 microg in rabbit models). To improve the efficacy, performance of rhBMP-2, and the safety of the delivery system for this protein, a more sophisticated system is required. METHODS: To fabricate one implant for one-side L4-L5 intertransverse process fusion, beta-tricalcium phosphate (beta-TCP) powder (300 microg), a polymer gel (PLA-DX-PEG block copolymer; 300 microg) and rhBMP-2 (7.5, 15, or 30 microg) were mixed and manually shaped to resemble a rod. Through a posterolateral approach, two implants were placed on both sides (1 per side) by surgery so as to bridge the transverse processes of adult New Zealand white rabbits (n = 27). In control animals, implants without rhBMP or autogenous cortico-cancellous bone chips from the iliaccrest were placed in a similar location. The lumbar vertebrae were recovered 6 weeks after surgery. The posterolateral fusion was examined by manual palpation, radiography, biomechanical testing, and histology. RESULTS: Rabbits that received 15 or 30 microg of rhBMP-2 showed consistent fusion. However, solid fusion was seen in 2 of 5 rabbits with autografting and rabbits that received 7.5 microg of rhBMP-2. Fusion was not observed in the rabbits that did not receive rhBMP-2. CONCLUSIONS: Consistent spinal fusion was obtained by implanting a biodegradable bone-inducing implant composed of beta-TCP, PLA-DX-PEG, and rhBMP-2 within a period of 6 weeks. The rhBMP-2 doses required for the spinal fusion were significantly lower than those reported previously.

Animals↗

PubMed2005

Hepatocyte growth factor contributes to fracture repair by upregulating the expression of BMP receptors.

UNLABELLED: Hepatocyte growth factor (HGF) is activated and the expression of BMP receptors (BMPRs) is induced around the fracture site during the early phase of fracture repair. HGF facilitates the expression of BMPRs in mesenchymal cells. This study suggests that HGF contributes to fracture repair by inducing the expression of BMPRs. INTRODUCTION: The precise mechanisms that control the upregulation of BMP, BMPRs, and other molecules involved in bone repair are not completely understood. In this study, we hypothesized that HGF, activated through the action of thrombin on the HGF activator, may enhance BMP action through the local induction of BMP or BMPRs. MATERIALS AND METHODS: Callus samples from tibial fractures in mice were harvested for immunohistochemical analysis of HGF and phosphorylated c-Met, for in situ hybridization of BMPRs, and for real-time RT-PCR analysis for the expression of HGF, c-Met, and BMPRs. To study the changes in gene expression of BMPRs in response to HGF, C3H10T1/2 cells were cultured with or without HGF and harvested for real-time RT-PCR and for Western blot analysis. To evaluate the contribution of HGF to the biological action of BMP2, C3H10T1/2 cells and primary muscle-derived mesenchymal cells were precultured with HGF and cultured with BMP2. In addition, the expression of the luciferase gene linked to the Id1 promoter containing the BMP responsive element and alkaline phosphatase (ALP) activity were assayed. RESULTS: Positive immunostaining of HGF and phosphorylated c-Met was detected around the fracture site at 1 day after the fracture was made. mRNA expression of BMPRs was increased 1 day after fracture and localized in mesenchymal cells at the fracture site. From an in vitro study, the expression of mRNA for BMPRs was elevated by treatment with HGF, but the expression of BMP4 did not change. Western blot analysis also showed the upregulation of BMPR2 by HGF treatment. The results from the luciferase and ALP assays indicated increased responsiveness to BMPs by treating with HGF. CONCLUSIONS: This study indicates that HGF is activated and expressed at the fracture site and that HGF induces the upregulation of BMPRs in mesenchymal cells. Furthermore, HGF may facilitate BMP signaling without altering the expression of BMP molecules.

Animals↗

PubMed2005

Objective assessment of reduced invasiveness in MED. Compared with conventional one-level laminotomy.

Microendoscopic discectomy (MED) has been accepted as a minimally invasive procedure for lumbar discectomy because of the small skin incision and short hospital stay required for this surgery. However, there are few objective laboratory data to confirm the reduced systemic responses in the early phase after this procedure. In order to substantiate the reduced invasiveness of MED compared to microdiscectomy (MD) or procedures involved in one-level unilateral laminotomy, the invasiveness of each surgical procedure was evaluated by measuring serum levels of biochemical parameters reflective of a post-operative inflammatory reaction and damage to the paravertebral muscles. Thirty-three patients who underwent lumbar discectomy or one-level unilateral laminotomy (MED in 15 cases, MD in 11 cases and one-level unilateral laminotomy in 7 cases with lumbar spinal canal stenosis) were included in this study. The serum levels of C-reactive protein (CRP) and creatine phosphokinase (CPK) were measured at 24 h after operation. Interleukin-6 (IL-6) and Interleukin-10 (IL-10) were measured at 2, 4, 8 and -24 h following the surgery to monitor the inflammatory response to the respective surgery. The post-operative serum CRP levels from both the MD and MED groups were significantly lower than those from the open laminotomy group. However, there was no significant difference in these serum levels between the MED and MD groups. The levels of IL-6 and IL-10 in the MED group during the first post-operative day were also significantly lower than those in the laminotomy group. When the MED and MD groups were compared, the IL-6 levels in the MED group were lower than in MD group at 2, 4 and 8 h after surgery, but the differences were not statistically significant. However, the level was significantly lower in the MED group at 24 h after surgery. In terms of IL-10, no significant difference was noted between the MED and MD groups over the study period. The changes in serum levels of post-operative inflammatory: markers (CRP, IL-6 and IL-10) in the early phase indicated reduced inflammatory reactions in MED as well as in MD when compared with classical open unilateral laminotomy. These data draw a direct link between the lower level of the inflammatory response and reduced invasiveness of MED. However, an indicator for muscle damage (CPK) appeared not to be affected by the type of surgical procedure used to correct disc herniation.

Adult↗

PubMed2005

Repair of an intercalated long bone defect with a synthetic biodegradable bone-inducing implant.

Recombinant human bone morphogenetic protein (rhBMP)-2 in a block copolymer composed of poly-D,L-lactic acid with randomly inserted p-dioxanone and polyethylene glycol (PLA-DX-PEG) as a carrier and porous beta-tricalcium phosphate (beta-TCP) blocks were used to generate a new fully absorbable osteogenic biomaterial. The bone regenerability of the rhBMP-2/PLA-DX-PEG/beta-TCP composite was studied in a critical-sized rabbit bone defect model. In an initial study, a composite of PLA-DX-PEG (250 mg) and beta-TCP (300 mg) loaded with or without rhBMP2 (50 microg) was implanted into a 1.5 cm intercalated bone defect created in a rabbit femur. Defects were assessed by biweekly radiography until 8 weeks postoperatively. The bony union of the defect was recognized only in the BMP-loaded group. To obtain further data on biomechanical and remodeling properties, another BMP-loaded composites group was made and observed up to 24 weeks. All defects were completely repaired without residual traces of implants. Anatomical and mechanical properties of the repaired bone examined by histology, 3-dimensional CT (3D-CT) and mechanical testing were essentially equivalent to the nonoperated-on femur at 24 weeks. These experimental results indicate that fully absorbable rhBMP-2/PLA-DX-PEG/beta-TCP is a promising composite having osteogenicity efficient enough for repairing large bone defects.

Absorbable Implants↗

PubMed2005

Augmentation of bone morphogenetic protein-induced bone mass by local delivery of a prostaglandin E EP4 receptor agonist.

Recombinant human bone morphogenetic protein (rhBMP) is viewed as a therapeutic cytokine because of its ability to induce bone. However, the high doses of rhBMP required for bone induction in humans remain a major hurdle for the therapeutic application of this protein. The development of a methodology that would effectively overcome the weak responsiveness to human BMP is highly desired. In the present study, we investigate the ability of a prostaglandin E EP4 receptor selective agonist (EP4A) to augment the bone-inducing ability of BMP in a biodegradable delivery system. A block copolymer composed of poly-D,L-lactic acid with random insertion of p-dioxanone and polyethylene glycol (PLA-DX-PEG, polymer) was used as the delivery system. Polymer discs containing rhBMP-2 and EP4A were implanted into the left dorsal muscle pouch of mice to examine the dose-dependent effects of EP4A. Fifty mice were divided into 5 groups based on the contents of rhBMP and EP4 in the polymer (group 1; BMP 5 microg EP4A 0 microg, group 2; BMP 5 microg EP4 3 microg, group 3; BMP 5 microg EP4 30 microg, group 4; BMP 5 microg EP4 300 microg, group 5; BMP 0 microg EP4 30 microg, n=10 each). All implants were harvested, examined radiologically, and processed for histological analysis 3 weeks after surgery. On dual-energy X-ray absorptiometry (DXA) analysis, the bone mineral content (BMC) of the ossicles was 6.52+/-0.80 (mg), 9.36+/-1.89, 14.21+/-1.27, and 18.75+/-2.31 in groups 1, 2, 3, and 4 respectively. In terms of BMC, the values of groups 3 and 4 were significantly higher than those of group 1. The mean BMC value of group 4 was approximately 3 times higher than that of group 1. No significant difference in body weight was noted among the groups during the experimental period. In summary, the presence of a prostaglandin E EP4 receptor selective agonist in the carrier polymer enhanced the bone-inducing capacity of rhBMP-2 with no apparent systemic adverse effects.

Alkaline Phosphatase↗

PubMed2004

A new bone-inducing biodegradable porous beta-tricalcium phosphate.

A new type of degradable biomaterial with bone-inducing capacity was made by combining porous beta-tricalcium phosphate (beta-TCP) with a delivery system for recombinant human bone morphogenetic protein-2 (rhBMP-2). The BMP delivery system consisted of a block copolymer composed of poly-D,L-lactic acid with random insertion of p-dioxanone and polyethylene glycol (PLA-DX-PEG), a known biocompatible and biodegradable material. The efficacy of this biomaterial in terms of its bone-inducing capacity was examined by ectopic bone formation in the dorsal muscles of the mouse. In the beta-TCP implants coated with the PLA-DX-PEG polymer containing more than 0.0025% (w/w) of rhBMP-2, new ectopic bone tissues with marrow were consistently found on the surface of implants. The radiographic density of beta-TCP was diminished in a time-dependent manner. On histological examination, numerous multinucleated osteoclasts with positive tartrate-resistant acid-phosphatase (TRAP) staining were noted on the surface of the beta-TCP. These experimental results indicate that beta-TCP implants coated with synthetic rhBMP-2 delivery system might provide effective artificial bone-graft substitutes with osteoinductive capacity and biodegradable properties. In addition, this type of biomaterial may require less rhBMP-2 to induce significant new bone mass.

Absorbable Implants↗

PubMed2004

A prostanoid receptor EP4 agonist enhances ectopic bone formation induced by recombinant human bone morphogenetic protein-2.

The anabolic effects of prostaglandin E(2) on bone are effected through the activation of EP4, a G protein-coupled receptor. In the present study, we examined the effects of a prostanoid receptor-selective agonist (ONO-4819) in an experimental system of ectopic bone formation using recombinant human bone morphogenetic protein-2 (rhBMP-2). Collagen pellets containing rhBMP-2 were implanted onto the back muscles of mice and then treated with ONO-4819 administered every 8 h by subcutaneous injection. The ossicles elicited ectopically by rhBMP-2 in mice treated with 30 microg/kg ONO-4819 were significantly larger in size and had a higher bone mineral density and bone mineral content when compared to the controls. We also noted that the anabolic effect of ONO-4819 was seen only in the early phase of the rhBMP-2-induced bone-forming process. These experimental results indicate that the EP4 receptor agonist enhances the rhBMP-2-induced bone formation through a selective effect on early stage mesenchymal cells, which in turn may result in increased responsiveness of the host animals to rhBMP-2.

Absorbable Implants↗

PubMed2004

Endothelialized networks with a vascular geometry in microfabricated poly(dimethyl siloxane).

One key challenge in regenerating vital organs is the survival of transplanted cells. To meet their metabolic requirements, transport by diffusion is insufficient, and a convective pathway, i.e., a vasculature, is required. Our laboratory pioneered the concept of engineering a vasculature using microfabrication in silicon and Pyrex. Here we report the extension of this concept and the development of a methodology to create an endothelialized network with a vascular geometry in a biocompatible polymer, poly(dimethyl siloxane) (PDMS). High-resolution PDMS templates were produced by replica-molding from micromachined silicon wafers. Closed channels were formed by bonding the patterned PDMS templates to flat PDMS sheets using an oxygen plasma. Human microvascular endothelial cells (HMEC-1) were cultured for 2 weeks in PDMS networks under dynamic flow. The HMEC-1 cells proliferated well in these confined geometries (channel widths ranging from 35 mum to 5 mm) and became confluent after four days. The HMEC-1 cells lined the channels as a monolayer and expressed markers for CD31 and von Willebrand factor (vWF). These results demonstrate that endothelial cells can be cultured in confined geometries, which is an important step towards developing an in vitro vasculature for tissue-engineered organs.

Biocompatible Materials↗

PubMed2004

Does chronic cervical myelopathy affect respiratory function?

OBJECT: Although respiratory function is often impaired by acute cervical spinal cord injury, changes in respiratory function in patients with chronic cervical myelopathy (CCM) are not well documented. The purpose of this study was to evaluate the respiratory function of patients with CCM. METHODS: Spirometric parameters were measured in 94 patients with CCM before they underwent expansive laminoplasty. These measurements were compared with those obtained in age- and sex-matched control group patients without myelopathy. The study patients were also subdivided into two groups: those with spinal compressive lesions above or below the C3-4 disc level were compared in terms of respiratory function. The vital capacity values measured in patients with CCM were significantly lower than those in the control group. In patients in whom spinal cord compression was present above C3-4, vital capacity values were lower than in patients in whom the compression level was below C3-4. The resting respiratory rate per minute was elevated in the CCM group. Peak expiratory flow rate was significantly decreased, and expiratory velocities at 50 and 25% of vital capacity were significantly increased in the CCM group. CONCLUSIONS: The results indicated that expiratory flow may be impaired or incomplete in patients with CCM. An underlying subclinical respiratory dysfunction appears to be associated with CCM.

Adult↗

PubMed2003

Formation of a mandibular condyle in vitro by tissue engineering.

PURPOSE: Mandibular reconstructive procedures often produce significant donor site morbidity. Recently, the use of minimally invasive techniques has been reported for mandibular reconstruction with decreased morbidity at the primary operative site. To date, these techniques have not addressed the graft donor site. We hypothesize that tissue-engineering techniques may be used to fabricate bone and thereby eliminate donor site morbidity. METHODS: Porcine mesenchymal stem cells (pMSCs) were isolated from the bone marrow of 3 Yucatan minipigs and grown in standard culture flasks. When they became near-confluent, cells were detached and replated with the addition of osteogenic supplements. A model of a porcine mandibular condyle was made and used to fabricate porous polymer scaffolds from biodegradable poly DL-lactic-co-glycolic acid (PLGA). Differentiated osteoblasts were transferred to the PLGA scaffold and cultured for 6 weeks in a rotational oxygen-permeable bioreactor system. The cultured constructs, consisting of scaffold and cells, were evaluated by gross, radiologic, and histologic examinations. RESULTS: The engineered constructs were white and hard and had a shape that closely resembled that of the model condyle. Plain radiographs demonstrated that the radiodensity of the construct was between that of the normal condyle and that of control scaffolds. Histologically, bone was observed on the entire surface of the PLGA scaffolds with an average thickness of 0.03 mm. Bone was not observed in the control scaffolds. CONCLUSION: In this pilot study, autologous tissue-engineered bone constructs were successfully made by combining biodegradable polymers and pMSCs.

Alkaline Phosphatase↗