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PubMed2004

Bioengineered teeth from cultured rat tooth bud cells.

The recent bioengineering of complex tooth structures from pig tooth bud tissues suggests the potential for the regeneration of mammalian dental tissues. We have improved tooth bioengineering methods by comparing the utility of cultured rat tooth bud cells obtained from three- to seven-day post-natal (dpn) rats for tooth-tissue-engineering applications. Cell-seeded biodegradable scaffolds were grown in the omenta of adult rat hosts for 12 wks, then harvested. Analyses of 12-week implant tissues demonstrated that dissociated 4-dpn rat tooth bud cells seeded for 1 hr onto PGA or PLGA scaffolds generated bioengineered tooth tissues most reliably. We conclude that tooth-tissue-engineering methods can be used to generate both pig and rat tooth tissues. Furthermore, our ability to bioengineer tooth structures from cultured tooth bud cells suggests that dental epithelial and mesenchymal stem cells can be maintained in vitro for at least 6 days.

Absorbable Implants↗

PubMed2001

Bioactivity of bioresorbable osteosynthetic devices made of hydroxyapatite/poly-DL-lactide composites: an experimental study.

AIM: To investigate the bioactivity of the self-designed biodegradable osteosynthetic devices made of resorbable hydroxyapatite microparticles/poly-DL-lactide (HA/PDLLA) composites. METHOD: Forty-three rabbits with a transverse transcondylar osteotomy of the distal femur were fixed intramedullary by a HA/PDLLA rod, the duration of follow-up were 3, 6, 12, 24 and 36 weeks. Histological, scanning electron microscopic (SEM), energy dispersive X-ray (EDX) and biomechanical analyses were done. RESULTS: Active new bone formation and direct bone-bonding were seen at the bone-implant interface. Generous apatite crystals deposited and grew on the surface of the composites at 3 approximately 6 weeks postoperation. The interfacial shear strength increased significantly. CONCLUSION: Through the incorporating of resorbable HA microparticles, specific bone-bonding and active osteogenic capacity is introduced. This kind of bioactivity, together with other properties such as sufficient mechanical strength, enhanced biocompatibility and radiopacity, which are intrinsically unobtainable in totally resorbable polymer/polymer systems, make the HA/PDLLA composites become a desirable material for the internal fixation of cancellous bone.

Absorbable Implants↗

PubMedDate not supplied

In vitro and in vivo degradation of lactic acid-based interference screws used in cruciate ligament reconstruction.

Nowadays, many degradable polymers are being used under the form of interference screws to fix the bone-tendon-bone autograft in anterior cruciate ligament reconstruction. However, little is known about the post-implantation fate of these screws, especially about the formation of crystalline residues which seems to be a critical factor for the success of surgery with temporary implants based on lactic and glycolic acid derived polymers (PLAGA). In an attempt to bring in some new insights, various high molecular weight stereoregular poly(lactide)s (PLAX with X = percentage of L-lactyl units) obtained by ring-opening polymerization of lactides in the presence of zinc-metal (PLA98-Zn), zinc lactate (PLA98-Znlac) or stannous octoate (PLA100-Sn), were processed by injection-molding to make interference screws to be compared. In vivo data were collected from screws implanted in sheep knees with follow ups ranging from 6 months to 5 years. Histology confirmed the heterogeneous degradation mechanism introduced nearly 10 years ago from in vitro investigations of homemade implants having simpler geometry. The effects of the initiator system (zinc- or tin derivatives) used to polymerize the lactide monomer on the properties of injection molded interference screws was also investigated in vitro in a phosphate buffer solution at 37 degrees C. Major differences in terms of hydrophilicity, hydrolysis rate and loss of mechanical properties were observed between PLA-Zinc and PLA-Tin. Discussion of the behavior of interference screws of different compositions was made on the basis of the present understanding of PLAGA morphology and degradation characteristics.

Absorbable Implants↗

PubMed2006

Accelerated degradation and improved bone-bonding ability of hydroxyapatite ceramics by the addition of glass.

Dense hydroxyapatite (HA) ceramics are useful bone substitutes, but they degrade minimally. One solution is to incorporate degradable materials in the HA. In this study, we manufactured glass-containing HA and investigated whether the degradability and bone-bonding ability of the HA were improved. The glass-containing HA was manufactured from a mixture of HA powder and 1.0 wt% glass powder. The control HA was manufactured from pure HA powder. In vitro degradability was evaluated by soaking in physiological saline, and a rabbit model was used to evaluate in vivo degradability and bone-bonding ability. Detaching tests were performed for all removed samples to quantify bone-bonding ability of each type of HA. The glass-containing HA showed higher degradability than the control HA, both in vitro and in vivo. The detaching failure load of the glass-containing HA was rapidly elevated after implantation and was higher than that of the control HA. Our results suggest that the dissolution of the added glass made the glass-containing HA degradable and that the detaching failure load of the glass-containing HA was elevated by reinforcement of the mechanical locking at the roughened interface. Incorporation of glass additives into HA can be concluded to be a good candidate for producing a bone substitute that can partially degrade and bond to bone firmly and rapidly.

Absorbable Implants↗

PubMedDate not supplied

Role for interleukin 1alpha in the inhibition of chondrogenesis in autologous implants using polyglycolic acid-polylactic acid scaffolds.

Significant challenges remain in generating tissue-engineered cartilage in immunocompetent animals. Scaffold materials such as polyglycolic acid lead to significant inflammatory reactions, inhibiting homogeneous matrix synthesis. This study examined the generation of tissue-engineered cartilage, using a polyglycolic acid-polylactic acid copolymer (Ethisorb; Ethicon, Norderstedt, Germany) in an autologous immunocompetent pig model. The goals of this study were to determine the role of interleukin 1alpha (IL-1alpha) in this system and to assess the effect of serum treatment on tissue generation. Porcine auricular chondrocytes were seeded onto Ethisorb disks cultured for 1 week in medium supplemented with either fetal bovine serum or serum-free insulin-transferrin-selenium supplement. Specimens were implanted autogenously in pigs with unseeded scaffolds as controls. After 1, 4, or 8 weeks, six specimens from each group were explanted and analyzed histologically (hematoxylin and eosin, safranin O, trichrome, and Verhoeff's staining) and biochemically (glycosaminoglycan content). The presence and distribution of IL-1alpha were assessed by immunohistochemistry. Histology revealed acute inflammation surrounding degrading scaffold. Cartilage formation was observed as early as 1 week after implantation and continued to increase with time; however, homogeneous matrix synthesis was not present in any of the specimens. Strong IL-1alpha expression was detected in chondrocytes at the implant periphery and in cells in the vicinity of degrading polymer. Histologically there was no significant difference between the experimental groups with respect to the amount of matrix synthesis or inflammatory infiltration. The glycosaminoglycan content was significantly higher in the serum-free group. These results suggest that inflammatory reactions against scaffold materials and serum components lead to the production of cytokines such as IL-1alpha that may inhibit cartilage tissue formation in autologous transplant models.

Absorbable Implants↗

PubMed2002

A concept for the treatment of various dental bone defects.

Untreated dental bone defects usually lead to resorption of alveolar bone. Filling these defects with bone substitute material prevents resorption of bone, preserves the alveolar ridge, and provides sufficient bone for immediate or subsequent implant placement. A variety of bone substitutes is available. They differ in origin, consistency, particle size, porosity, and resorption characteristics. We have treated almost 1000 bony defect sites in 267 patients with the bone regeneration material Cerasorb. Being resorbed simultaneously with the formation of new bone, it is completely replaced by the patient's own vital bone within 6 to 12 months. The representative cases described in this paper demonstrate the successful use of the pure-phase beta-tricalcium phosphate ceramic in the treatment of all dental bone defects.

Absorbable Implants↗

PubMedDate not supplied

Investigation of early bone formation using resorbable bioactive glass in the rat mandible.

Recent advances in biomaterial technology have made alloplastic bone substitutes more predictable when used with the proper clinical methodology in carefully selected patients. In this animal study, early bone formation using a novel resorbable bioactive glass in the repair of surgically created bony defects in the rat mandible was investigated. Biopsies taken from the implanted sites after 1, 2, 3, 4, 8, and 16 weeks were examined histologically by means of standard cell-staining techniques. In addition, an electron probe microanalyzer was used to determine the presence and distribution of specific elements in samples taken after 16 weeks. Results indicated the early stage of osteoconductive bone growth after approximately 4 weeks. After 16 weeks, electron probe micro-analyzer scans indicated the formation of a calcium-phosphate shell formed in situ and the resorption of silica to background levels.

Absorbable Implants↗

PubMed2006

In vivo biodegradability and biocompatibility evaluation of novel alanine ester based polyphosphazenes in a rat model.

Amino acid ester substituted polyphosphazenes are attractive candidates for various biomedical applications because of their biocompatibility, controllable hydrolytic degradation rates, and nontoxic degradation products. In this study, the biocompatibility of three L-alanine ethyl ester functionalized polyphosphazenes was evaluated in a subcutaneous rat model. The polymers used in the study were poly[bis(ethylalanato)phosphazene] (PNEA), poly[(50% ethylalanato) (50% methylphenoxy) phosphazene] (PNEA(50)mPh(50)), and poly[(50% ethylalanato)(50% phenyl phenoxy) phosphazene] (PNEA(50)PhPh(50)). Polymer disks of diameter 7.5 mm were prepared by a solvent evaporation technique and were implanted subcutaneously in rats. After 2, 4, and 12 weeks, the polymer along with the surrounding tissues were excised, prepared, and viewed by light microscopy to evaluate the tissue responses of the implanted polymers. The tissue responses were classified as minimal, mild, or moderate, based on a biocompatibility scheme developed in our laboratory. Minimal inflammation was characterized by the presence of few neutrophils, erythrocytes, and lymphocytes; mild response was characterized by the predominant presence of macrophages, fibroblasts, or giant cells; and moderate inflammation was characterized by the abundance of macrophages, giant cells, and by the presence of tissue exudates. The in vivo degradation profiles of the polymers at various time points were evaluated by gel permeation chromatography (GPC). PNEA and PNEA(50)mPh(50) matrices elicited varying levels of tissue responses during the 12-week implantation period. At 2 weeks both polymers evoked a moderate response, and by 12 weeks the response was found to be mild. However, PNEA(50)PhPh(50) elicited a mild response at the end of 2 weeks and demonstrated a further decreased inflammatory response after 12 weeks. The in vivo degradation of the polymers was followed by determining the molecular weights of the explanted polymer disks. PNEA and PNEA(50)mPh(50) disks showed significant decrease in molecular weight after 2 weeks of implantation. The molecular weights of PNEA and PNEA(50)mPh(50) residues could not be determined by GPC after 12 weeks of implantation because of almost complete degradation. On the other hand the in vivo degradation of PNEA(50)PhPh(50) was found to be slow, with a 63% loss in molecular weight in 12 weeks. Furthermore, this polymer maintained its shape and structure during the entire study. Thus, these polymers demonstrated excellent tissue compatibility and in vivo biodegradability and can be potential candidates for various biomedical applications.

Absorbable Implants↗

PubMed2003

Femoral fixation of hamstring tendon autografts using the TransFix device with additional bone grafting in an anteromedial portal technique.

BACKGROUND: The femoral fixation of hamstring tendon grafts by a cross-pin is an established method with excellent biomechanical properties. Until now, this surgical procedure was associated with a transtibial placement of the femoral tunnel and a graft-tunnel diameter mismatch due to the different volumes of the tendon loop and the tendon strands. METHODS: By use of an electrical knee positioning device, the transfixation technique can be performed safely through the anteromedial arthroscopic portal (transarticular technique), reaching the optimal lateral '10:30' position in the intercondylar notch. By use of a specific harvesting and implantation device, a cancellous bone plug is harvested and inserted into the femoral tunnel, thus stabilizing the tendon bundle and eliminating dead space in the tunnel. CONCLUSION: The femoral cross-pin guarantees a secure anchorage of the graft, drilling through the anteromedial portal eases optimum tunnel placement, and the insertion of a solid cancellous bone plug eliminates the femoral graft-tunnel diameter discrepancy and improves the press-fit contact between graft and tunnel wall. The long-term benefit of this technical modification remains to be proven.

Absorbable Implants↗

PubMed2002

Effect of recombinant human bone morphogenetic protein-2 on bone formation in alveolar ridge defects in dogs.

This study was designed to evaluate the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with poly D, L lactic-co-glycolic acid (PLGA)/gelatin sponge complex (PGS) on the formation of bone in critically sized marginal defects of the mandible in dogs. Three months after extraction of the pre-molar teeth, rectangular bone defects (10 x 8 x 7 mm) were made in both sides of the mandible. A PGS block soaked in rhBMP-2 (400 microgram/ml) was implanted into one defect (BMP (+) group). As control, an untreated PGS block was implanted into the contralateral defect (BMP (-) group). 2, 4, 8, and 12 weeks after implantation, the defects were examined. In the BMP (+) group, newly formed bone was found in all defects from 4 weeks onward and was marked at 12 weeks. In contrast, the BMP (-) group showed no appreciable new bone formation, even at 12 weeks. Moreover, density of newly formed bone in the BMP (+) group was similar to that of the surrounding cortical bone at 12 weeks. These findings suggest that rhBMP-2/PGS is an effective bone substitute for reconstructive surgery of the dog mandible.

Absorbable Implants↗

PubMed2000

[Biodegradable implants in fracture fixation: state of the art].

Operative fracture repair in trauma surgery is currently performed using metal implants. These metal implants often are removed during a second, retrieval operation. Biodegradable fracture fixation devices have been used clinically since the late seventies. Most bioresorbable implants are manufactured from polymers. The polylactides, polyglycolides and co-polymers slowly degrade into small components that are excreted from the human body via natural pathways and removal operations after fracture surgery are not necessary. Due to the limited mechanical properties, the polymer screws and pins are mostly used in the treatment of non weight-baring simple fractures of the ankle, elbow, hand and foot. In view of the progressing technical developments, new materials will be developed and tested for clinical use in the coming decades.

Absorbable Implants↗

PubMed2006

Repair of tendon defect with dermal fibroblast engineered tendon in a porcine model.

Harvesting autologous tenocytes for tendon engineering may cause secondary tendon defect at the donor site. Dermal fibroblasts are an easily accessible cell source and do not cause major donor site defect. This study aims to explore the possibility of tendon engineering using dermal fibroblasts. A total of 45 hybrid pigs were randomly divided into three groups: experimental group (n = 15)--repair of tendon defect with a dermal fibroblast engineered tendon; control group 1 (n = 15)--repair of defect with a tenocyte engineered tendon; and control group 2 (n = 15)-repair of defect with a scaffold alone. Both autologous dermal fibroblasts and tenocytes were seeded on polyglycolic acid (PGA) unwoven fibers to form a cell-scaffold construct and cultured in vitro for 7 days before in vivo implantation to repair a defect of flexor digital superficial tendon. Specimens were harvested at weeks 6, 14, and 26 for gross, histological, and mechanical analyses. Microscopy revealed good attachment of both dermal fibroblasts and tenocytes on PGA fibers and matrix production. In vivo results showed that fibroblast and tenocyte engineered tendons were similar to each other in their gross view, histology, and tensile strength. At 6 weeks, parallel collagen alignment was observed at both ends, but not in the middle in histology, with more cellular components than natural tendons. At weeks 14 and 26, both engineered tendons exhibited histology similar to that of natural tendon. Collagens became parallel throughout the tendon structure, and PGA fibers were completely degraded. Interestingly, dermal fibroblast and tenocyte engineered tendons did not express type III collagen at 26 weeks, which remained observable in normal pig skin and control group 2 tissue using polarized microscopy, suggesting a possible phenotype change of implanted dermal fibroblasts. Furthermore, both fibroblast and tenocyte engineered tendons shared similar tensile strength, about 75% of natural tendon strength. At 6 weeks in control group 2, neo-tissue was formed only at the peripheral area by host cells. A cord-like tissue was formed at weeks 14 and 26. However, the formed tissue was histologically disorganized and mechanically weaker than both cell-engineered tendons (p < 0.05). These results suggest that dermal fibroblasts may have the potential as seed cells for tendon engineering.

Absorbable Implants↗

PubMed2002

[Development of new, biodegradable implants].

The advantage of biodegradable implants is that they do degrade after they have fulfilled their function. Therefore, a second operation for removing metal implants is not necessary. Additionally, the healing process may be stimulated by the successive loss of the mechanical properties of the implant during degradation, corresponding with the increasing loading on the healing tissue. The most important materials are polylactide, polyglycolide and their copolymers, and polydioxanone. The mechanical properties of these polymers were improved by special fabrication techniques. Nevertheless, the materials have disadvantages relating to their stiffness and relaxation behavior. Therefore, their use has to be restricted to nearly unloaded situations. The degradation behavior of the materials can be controlled by the production of copolymers and by the molecular weight of the polymers. The degradation behavior cannot be predicted exactly in vivo, as it is influenced not only by the chemistry and the implant design but also by the localization of the implant in the tissue. In general, the biocompatibility of the polymers used today is good and the observed complication rate is very low. Osteolytic reactions, which can sometimes be observed, have no clinical consequences in most instances. The clinical applications comprise resorbable pins and screws for the fixation of small bony fragments, interference screws for the surgery of the anterior cruciate ligament, resorbable augmentation devices for ligaments and tendons, resorbable membranes for guided bone regeneration in maxillofacial surgery, and a lot more. Future developments are expected in the field of tissue engineering and drug release.

Absorbable Implants↗

PubMed2004

Biomechanical comparison of bioabsorbable cervical spine interbody fusion cages.

STUDY DESIGN: In vitro biomechanical study of bioabsorbable cervical spine interbody fusion cages using a sheep model. OBJECTIVES: The purpose of this study was to evaluate the segmental stability provided by 2 new developed bioabsorbable cervical spine interbody fusion cages and to compare it with a tricortical iliac crest bone graft and a titanium meshed interbody fusion cage. Further, the biomechanical effect of an additional anterior plate instrumentation was determined. SUMMARY AND BACKGROUND DATA: Despite the initial favorable results, the long-term effects of metallic cage devices on spinal motion segments are still unknown. Furthermore, shortcomings of metallic cages like migration, adjacent level degeneration, stenotic myelopathy, and artifacts in postoperative radiologic assessment have already been reported. Bioabsorbable cages have been designed to avoid these complications. Currently, no information is available about the biomechanical properties of bioabsorbable cervical spine interbody fusion cages. METHODS: Forty sheep cervical spines (C2-C5) were tested in flexion, extension, axial rotation, and lateral bending with a nondestructive stiffness method using a nonconstrained testing apparatus. First, the motion segment C3-C4 was tested intact. After complete discectomy, the following groups were evaluated: autologous iliac crest bone graft, titanium mesh cylinder (Harms, DePuy AcroMed), bioabsorbable PDLLA-cage (experimental), and bioabsorbable Resorbon cage (Biomet Merck). Further, all implants were tested with an additional anterior plate instrumentation. The mean apparent stiffness, range of motion, neutral zone, and elastic zone were calculated from the corresponding load-displacement curves. RESULTS: No significant difference in range of motion and segmental stiffness among the tricortical iliac crest bone graft, meshed titanium Harms cage, and PDLLA-cage could be determined. The Resorbon cage significantly (P < 0.05) decreased range of motion and increased stiffness in rotation and flexion in comparisonto all tested implants and the intact motion segment. An additional anterior plate significantly (P < 0.05) decreased range of motion and increased stiffness in flexion and extension. CONCLUSION: In this study, bioabsorbable cages demonstrated biomechanical in vitro properties equal or superior to metallic cages. From the biomechanical point of view, bioabsorbable cages, especially the Resorbon cage, may be a viable alternative to current metallic interbody cage devices. However, animal experimental in vivo evaluation of bioabsorbable cervical spine interbody fusion cages still has to be performed.

Absorbable Implants↗

PubMed2005

Localized ridge augmentation with allogenic block grafts prior to implant placement: case reports and histologic evaluations.

The placement of dental implants is based on the amount of alveolar bone present in the edentulous site to be reconstructed. Insufficient alveolar contours may require bone grafting procedures to restore an adequate bone volume before implant placement. Larger osseous defects often require block grafts harvested from the symphysis or the ramus buccal shelf region. These provide adequate donor sites to harvest a graft sufficient to restore a significant defect in the osseous structures planned for implant placements. Autogenous block grafts have been well established to reconstruct these types of defects prior to implant placement procedures. However, surgical complications associated with the unfavorable anatomical structures and the necessity of large donor sites (e.g., symphysis and ramus buccal shelf) have led to the use of allogenic grafting materials. Recent developments in allogenic grafting materials have lead to the development of a corticocancellous block graft harvested from the iliac crest region. This study evaluates the clinical indications of these allogenic graft materials to replace compromised alveolar bone defects both horizontal and vertical in nature. The analysis is supported by re-entry procedures and histologic evaluations to substantiate predictability.

Absorbable Implants↗

PubMed2001

Novel adhesion prevention membrane based on a bioresorbable copoly(ester-ether) comprised of poly-L-lactide and Pluronic: in vitro and in vivo evaluations.

Block copolymers consisting of poly(L-lactide) (PLLA) and poly(oxyethylene-co-oxypropylene), with various compositions, were synthesized and characterized in vitro and in vivo for their application as postoperative adhesion prevention membranes. It was found that the flexibility and degradability of the cast films of the block copolymers grew with increasing Pluronic F68 [PN; poly(oxyethylene-co-oxypropylene] composition. The receding contact angle of the copolymer films against water became lower than that of the PLLA film, because the surface was predominantly covered with more hydrophilic PN segments in a wet state. This surface property significantly affects the cell attachment property of the copolymer films, and the fibroblasts cultured on the films exhibit a spheroid-like morphology. The copolymer films subcutaneously implanted in the back of rats induced milder tissue responses compared with PLLA homopolymers, because of the increased surface hydrophilicity in the former. In vivo evaluation using a uterus horn model in rats revealed that the performance of these copolymer films as an adhesion-prevention membrane is comparable to that of a conventionally utilized membrane of oxidized regenerated cellulose. These results indicate that the copolymer films are biocompatible materials with controllable mechanical properties and biodegradability as adhesion-prevention membranes.

3T3 Cells↗

PubMed2004

Restoration of function after spinal cord transection using a collagen bridge.

The restoration of function of transected adult mammalian spinal cord without living tissue has not been reported previously. We report the first success of functional restoration of transected spinal cord without living tissue. We grafted collagen filaments parallel or transverse to the axis of the spinal cord to bridge 5-mm defects of 47 adult rat spinal cords. Twenty-five rats were used as a control. Of the 72 rats, 42 rats survived the experimental period. At 4 weeks postoperatively, regenerated axons crossed the proximal and distal spinal cord-implant interfaces in all 5 rats of the parallel-grafted group. At 12 weeks postoperatively, the rats in the parallel-grafted group (8 rats) could walk, run, and climb with hind-forelimb coordination. The somatosensory-evoked potentials were seen. Results suggest that the collagen filaments support the axonal regeneration of the transected spinal cord and the restoration of function when grafted parallel to the axis of the spinal cord. The functional restoration appeared to be permanent, raising the possibility of therapeutic application in humans.

Absorbable Implants↗

PubMed2005

Evaluation of biodegradable synthetic scaffold coated on arterial prostheses implanted in rat subcutaneous tissue.

Polyester arterial prostheses impregnated with various synthetic biodegradable materials and with gelatin were implanted subcutaneously in rats for 3-180 days. The inflammation was assessed by quantifying the activity of alkaline phosphatase and by histology. The degradation of the scaffold materials was determined by scanning electron microscopy (SEM), size exclusion chromatography (SEC), and differential scanning calorimetry (DSC). The alkaline phosphatase activity induced by the polymer-impregnated grafts was similar to that induced by the non-impregnated controls during most of the post-implantation periods. Histological studies revealed that the acute inflammatory response was moderate to mild and was similar for all types of specimens, except for the gelatin-impregnated grafts that induced a severe acute inflammation during the first 2 weeks post-implantation. At 4 and 6 months, significant disintegration of the scaffold was observed, accompanied by enhanced tissue infiltration and a reactivation of the acute inflammatory phase. Linear and exponential degradation rates of the synthetic polymers were described. The relative degradation rates of the biodegradable polymers were ranked as following: PLLACL > PDLLA > PLLA > PCEL. In conclusion, biodegradable polymers may provide an option as sealant/scaffolding materials for vascular prosthesis. It is suggested that the degradation rate of the polymer scaffolding materials should be higher to achieve early healing while without inducing strong inflammation.

Absorbable Implants↗