Differential effects of bone morphogenetic protein-2 and transforming growth factor-beta1 on gene expression of collagen-modifying enzymes in human adipose tissue-derived mesenchymal stem cells.

Adipose tissue-derived mesenchymal stem cells (AT-MSCs) in combination with bone morphogenetic protein-2 (BMP-2) or transforming growth factor-beta1 (TGF-beta1) are under evaluation for bone tissue engineering. Posttranslational modification of type I collagen is essential for functional bone tissue with adequate physical and mechanical properties. We investigated whether BMP-2 (10-100 ng/mL) and/or TGF-beta1 (1-10 ng/mL) affect gene expression of alpha2(I) procollagen and collagen-modifying enzymes, that is, lysyl oxidase and lysyl hydroxylases 1, 2, and 3 (encoded by PLOD1, 2, and 3), by human AT-MSCs. BMP-2, but not TGF-beta1, increased alkaline phosphatase activity after 28 days, indicating osteogenic differentiation of AT-MSCs. At day 4, both BMP-2 and TGF-beta1 upregulated alpha2(I) procollagen and PLOD1, which was downregulated at day 28. TGF-beta1, but not BMP-2, downregulated PLOD3 at day 28. Lysyl oxidase was upregulated by TGF-beta1 at day 4 and by BMP-2 at day 7. Neither BMP-2 nor TGF-beta1 affected PLOD2. In conclusion, these results suggest that AT-MSCs differentially respond to BMP-2 and TGF-beta1 with changes in gene expression of collagen-modifying enzymes. AT-MSCs may thus be able to appropriately modify type I collagen to form a functional bone extracellular matrix for tissue engineering, dependent on the growth factor added.

PLDLA mesh and 60/40 biphasic calcium phosphate in iliac crest regeneration in the goat.

Although morbidity of the iliac crest after grafting has been reported to occur frequently, it is the most widely used donor site. A proper regeneration of the defect could decrease morbidity. The purpose of this study was to evaluate the efficacy of two types of reconstruction of standardized critical size defects of the iliac crest after 3, 6, and 12 months. Standardized critical defects in iliac crests were bilaterally reconstructed in 28 goats randomly with (1) no reconstruction (group A); (2) a bioresorbable polylactide mesh (group B); or (3) 60/40 biphasic calcium phosphate (BCP) granules placed within a bioresorbable mesh (group C). At follow up, the iliac crests were harvested for histologic, histomorphometric, and radiologic analyses. The defects treated with "mesh-BCP" (group C) showed a significantly (p = 0.03) larger area with diffuse bone formation, while only a small area of high density trabecular bone ingrowth was observed in the "no reconstruction" (group A) and "mesh group" (group B). However, no difference in the total volume of bone was observed; in group C, the bone was more diffusely spread over the defect. Substitution of the BCP granules by trabecular bone did not start before 6 months. At the 12 months time point, extensive resorption of BCP was found because of phagocytic activity of numerous multinucleated giant cells. We confirm the positive influence of BCP on bone formation but due to a slow rate of resorption of BCP, regeneration takes a relatively long period of time.

Effect of long-term preservation on the mechanical properties of cortical bone in goats.

BACKGROUND AND PURPOSE: Bones used in mechanical studies are frequently harvested from human cadavers that have been embalmed in a buffered formaldehyde solution. It has been reported that formaldehyde fixation or freezing hardly affects the mechanical properties of bone after a storage period of several weeks. However, human cadaver bones are usually stored for longer periods of time before use. We therefore investigated the effects of long-term embalming or freezing on the mechanical properties of cortical bone. METHODS: After 5 different storage periods (ranging from 0 to 12 months), goat femora and humeri were used to evaluate the effect of embalming and freezing on torsion, and on bending stiffness and strength. The effect on hardness and bone mineral density (BMD) was also evaluated. RESULTS: Even after 1 year, no statistically significant differences could be found in stiffness, strength, and energy absorption when we compared embalmed or frozen bones to a fresh reference group. In addition, although we found no significant change in BMD, there appears to be a tendency to increasing hardness. INTERPRETATION: We found that there was no effect on the mechanical properties of bone after storage periods of 1 year. We conclude that embalmed or frozen bones can safely be used for mechanical testing, at least for storage periods of up to one year.

Adjacent segment degeneration: observations in a goat spinal fusion study.

STUDY DESIGN: The adjacent discs of 13 goats, originally used in a lumbar spinal fusion model study, were analyzed for symptoms of intervertebral disc degeneration by means of magnetic resonance imaging (MRI), macroscopy, and histology. These goats were followed for 6 months and the results were compared with 6 control goats. OBJECTIVE: To evaluate the development of adjacent segment disc degeneration in vivo in a goat lumbar spinal fusion model. SUMMARY OF BACKGROUND DATA: There is ongoing debate on whether adjacent segment degeneration (ASD) develops through increased biomechanical load on discs adjacent to fusion sites, or by the natural process of pre-existing degenerative disease. Animal models offer an opportunity to separate these factors by evaluating the development of ASD in nondegenerated animal spines. METHODS: In a spinal fusion model study 2 segments (L3-L4 and L1-L2) were fixated and followed for 3 months (n = 6) and 6 months (n = 7) in 13 skeletally mature goats. Two adjacent discs (T13-L1 and L4-L5), 1 interjacent disc (L2-L3) and a control disc (L5-L6) were analyzed by means of magnetic resonance imaging, macroscopy, and histology. These results were compared with the discs of 6, nonoperated "normal" goats. RESULTS: No differences were observed in the adjacent and interjacent intervertebral discs after both follow-up periods. However, severe degenerative changes were observed in the L5-L6 level, originally included as controls. CONCLUSION: Large animal fusion models offer an excellent opportunity to study ASD in vivo, as pre-existing degenerative disc disease is not present and biomechanical effects of the fusion can be studied more isolated. Our results suggest that adjacent disc degeneration does not develop in our spinal goat fusion model. There is, however, an increased risk of disc degeneration in the L5-L6 level through an unclear mechanism.

Reproducible long-term disc degeneration in a large animal model.

STUDY DESIGN: Twelve goats were chemically degenerated and the development of the degenerative signs was followed for 26 weeks to evaluate the progression of the induced degeneration. The results were also compared with a previous study to determine the reproducibility. OBJECTIVES: The purpose of this study was determine whether this Chondroitinase ABC (CABC) induced goat model is reproducible and to study the development of the degeneration in time up to 26 weeks. SUMMARY OF BACKGROUND DATA: Injecting CABC into goat intervertebral discs results in mild disc degeneration after 12 weeks. Spontaneous recovery or leveling off of the degeneration has been reported before and is relevant when the goat model is used in regeneration studies. Reproducibility of the induced degeneration is relevant as well. METHODS: Twelve goats were used in this study. The development of degeneration was studied after the injection of 0.25 U/mL CABC intradiscally. The development of degenerative signs was studied after 18 (n = 6) and 26 (n = 6) weeks by means of radiograph, magnetic resonance imaging, macroscopic analysis, and histology and biochemical evaluation. The induced degeneration was compared with the results from a previous study, in which degeneration was induced similarly and analysis was performed after 12 weeks. RESULTS: The severity of the degenerative signs was mild and was consequently present in all parameters analyzed. When compared with the results after 12 weeks, the degeneration was similar in the present study. Spontaneous recovery was not observed up to 26 weeks. CONCLUSION: The injection with CABC in the intervertebral disc reproducibly results in mild disc degeneration in the goat. These findings corroborate the goat model as a suitable large animal model to evaluate mild disc degeneration and potential new therapies.

Time-dependent mechanical strength of 70/30 Poly(L, DL-lactide): shedding light on the premature failure of degradable spinal cages.

STUDY DESIGN: In vitro studies on the mechanical strength of 70/30 poly(l,dl-lactic acid) (70/30 PLDLLA) cages. OBJECTIVE: To evaluate the effect of loading rate, humidity, temperature, and continuous static loading on the strength of 70/30 PLDLLA, to elucidate the mechanism of premature failure of degradable spinal cages observed in earlier studies. SUMMARY OF BACKGROUND DATA: Degradable 70/30 PLDLLA cages have been designed to withstand mechanical loads in a goat lumbar spine for at least 6 months. Yet mechanical failure was observed after only 3 months in vivo. We hypothesize that this observation can be related to the time-dependent nature of the polymer. METHODS: Degradable 70/30 PLDLLA cages were loaded to failure at loading rates between 10 and 10 mm/s under standard loading conditions (in air at room temperature: +/-23 degrees C). The experiments were also done at body temperature (37 degrees C) and under wet conditions. Furthermore, we determined the time-to-failure for 70/30 PLDLLA cages subjected to loads well below their instantaneous mechanical strength. RESULTS: The mechanical strength of 70/30 PLDLLA cages was lower for lower loading rates, higher temperature, and higher humidity. The cages already failed within less than 5 minutes when statically loaded at 75% of their strength, and within 1 day when loaded at about 50% of their strength. Extrapolation predicts cage failure at 3 months when loaded at 25% of their strength. CONCLUSION: Premature failure of 70/30 PLDLLA cages, as observed in vivo in earlier studies, is owing to mechanical loading and the time-dependent mechanical properties of the material. The standards for mechanical testing of implants made of strongly time-dependent materials like polylactide should be reconsidered.

Intravenous administration of the conditionally replicative adenovirus Ad5-Delta24RGD induces regression of osteosarcoma lung metastases.

Metastatic osteosarcoma (OS) has a very poor prognosis. New treatments are therefore wanted. The conditionally replicative adenovirus Ad5-Delta24RGD has shown promising anti-tumor effects on local cancers, including OS. The purpose of this study was to determine whether intravenous administration of Ad5-Delta24RGD could suppress growth of human OS lung metastases. Mice bearing SaOs-lm7 OS lung metastases were treated with Ad5-Delta24RGD at weeks 1, 2 and 3 or weeks 5, 6 and 7 after tumor cell injection. Virus treatment at weeks 1-3 did not cause a statistically significant effect on lung weight and total body weight. However, the number of macroscopic lung tumor nodules was reduced from a median of >158 in PBS-treated control mice to 58 in Ad5-Delta24RGD-treated mice (p = 0.15). Moreover, mice treated at weeks 5-7 showed a significantly reduced lung weight (decrease of tumor mass, p < 0.05), a significantly increased body weight gain (decrease of disease symptoms, p < 0.005) and a reduced number of macroscopic lung tumor nodules (median 60 versus > 149, p = 0.12) compared to PBS treated control animals. Adenovirus hexon expression was detected in lung tumor nodules at sacrifice three weeks after the last intravenous adenovirus administration, suggesting ongoing viral infection. These findings suggest that systemic administration of Ad5-Delta24RGD might be a promising new treatment strategy for metastatic osteosarcoma.

In vivo release of the antimicrobial peptide hLF1-11 from calcium phosphate cement.

We studied the release of human lactoferrin 1-11 (hLF1-11), a potent antimicrobial peptide, in an animal model. Calcium phosphate cement with 50 mg/g hLF1-11 was injected into the femoral canal of 12 rabbits. One, 3, and 7 days later, four animals were terminated, and the femora excised. Sections of bone and cement were removed for histological analysis. We used liquid chromatography-mass spectrometry/mass spectrometry for semiquantitative determination of the hLF1-11 concentration. Blood samples were drawn for leukocyte count and differentiation to identify a potential immunomodulating effect of hLF1-11. After an initial burst release, the hLF1-11 concentration in cement and bone decreased steadily. This in vivo release profile is consistent with earlier in vitro studies. Tissue ingrowth into the cement, without signs of inflammation or necrosis, was observed. Leukocytosis or a shift in leukocyte differentiation did not occur. The carrier released over 99% of the hLF1-11, resulting in peak concentrations at the cement-bone interface. This indicates that hLF1-11 could become a valuable prophylactic agent in osteomyelitis treatment.

Long term follow-up of a patient with disseminated spinal hydatidosis.

A rare case of a 27-year-old male patient with disseminated sacral hydatidosis is presented. Because the diagnosis was missed initially, the patient underwent only partial resection of the tumour to obtain tissue for histology. The resection was followed by deep wound infection, and re-exploration had to be performed, thereby resecting the remaining cyst tissue and the S1-S3 vertebral bodies. Adjuvant anti-helminthic therapy was started postoperatively. Unfortunately, the hydatid cyst further progressed and could only be controlled with multiple decompression procedures and continuance of anti-helminthic therapy. We review the diagnosis, treatment and prognosis of this uncommon condition, which is a serious challenge for the spinal surgeon.

Stem cells from adipose tissue allow challenging new concepts for regenerative medicine.

The perspective of an innovative new concept integrating tissue-engineering techniques with an established surgical technique is described. The focus is primarily on a one-step surgical procedure using adipose tissue-derived mesenchymal stem cells, a calcium phosphate scaffold as a carrier, and a bioresorbable polymer cage to facilitate spinal interbody fusion. We address the harvesting and processing of clinically relevant quantities of adipose tissue-derived mesenchymal stem cells, triggering of these stem cells toward lineage-specific differentiation, seeding of the triggered stem cells on a bioresorbable scaffold, and implantation of the resulting tissue-engineered construct. The integrated steps can be accomplished within one surgical procedure in a surgical theater. Although the proposed concept has been developed for spinal fusion, potential application in other surgical disciplines is presumed realistic.

Enhanced tumor cell kill by combined treatment with a small-molecule antagonist of mouse double minute 2 and adenoviruses encoding p53.

Strategies to treat cancer by restoring p53 tumor suppressor functions are being actively investigated. These approaches range from expressing an exogenous p53 gene in p53 mutant cancers to antagonizing a p53 inhibitor in p53 wild-type (WT) cancer cells. In addition, exogenous p53 is used to strengthen the anticancer efficacy of oncolytic adenoviruses. Many cancers express high levels of the major negative regulator of p53, mouse double minute 2 (MDM2) protein. Recently, a novel class of highly potent and specific MDM2 antagonists, the Nutlins, was identified. We envisioned that Nutlins could protect both endogenous and exogenous p53 from MDM2-mediated inactivation. We therefore investigated treating human cancer cells with a combination of adenovirus-mediated p53 gene therapy and Nutlin. Combination treatment resulted in broadly effective cell kill of p53 WT and p53-negative cancer cells. Cytotoxicity was associated with profound cell cycle checkpoint activation and apoptosis induction. We also tested Nutlin in combination with oncolytic adenoviruses. Nutlin treatment accelerated viral progeny burst from oncolytic adenovirus-infected cancer cells and caused an estimated 10- to 1,000-fold augmented eradication of p53 WT cancer cells. These findings suggest that Nutlins are promising compounds to be combined with p53 gene therapy and oncolytic virotherapy for cancer.

Sterilization and strength of 70/30 polylactide cages: e-beam versus ethylene oxide.

STUDY DESIGN: In vitro and in vivo studies on the degradation of 70/30 poly(L,DL-lactide) (PLDLLA) cages. OBJECTIVE: To evaluate the effect of e-beam and ethylene oxide sterilization on degradation and strength. SUMMARY OF BACKGROUND DATA: e-beam-sterilized PLDLLA cages were shown to maintain mechanical strength for at least 6 months during degradation studies in vitro. Yet failure of the cages was observed after only 3 months in vivo. We hypothesized that degradation characteristics and mechanical strength could be improved by sterilizing the cages through ethylene oxide (EtO) instead of e-beam. METHODS: PLDLLA cages were sterilized either by e-beam or EtO, and degraded in phosphate-buffered saline. Each month, cages were compressed until failure. Inherent viscosity was determined as a measure of degradation. For the in vivo evaluation, e-beam- or EtO-sterilized cages were implanted at L3-L4 in a standardized goat model. After 3 or 6 months, retrieved segments were scanned by high-resolution magnetic resonance imaging. Also, inherent viscosity of the polymer was measured. RESULTS: e-beam sterilization strongly decreased inherent viscosity of PLDLLA compared with EtO sterilization, but initial strength was only affected marginally. After 6 months, the strength of the e-beam-sterilized cages dropped, while that of EtO-sterilized cages was maintained. Degradation in vivo was slightly faster than in vitro. In both groups, however, mechanical failure occurred at 3 months after implantation. CONCLUSIONS: Inherent viscosity decreases with degradation time, but strength only decreases when inherent viscosity is below a certain threshold. Above this threshold, mechanical strength is a property of the polymer and independent of inherent viscosity. e-beam sterilization strongly decreases inherent viscosity and thus advances mechanical degradation. EtO sterilization delays degradation but does not increase initial strength. Early failure of PLDLLA cages in the goat model thus is unrelated to sterilization method and requires further study.

Internal thoracic vessels used as pedicle graft for anastomosis with vascularized bone graft to reconstruct C7-T3 spinal defects: a new technique.

STUDY DESIGN: A report of 4 cases of primary bone tumors (3 cases) or infection (1 case) at the cervicothoracic junction treated with resection-reconstruction. OBJECTIVES: To document a new technique using the internal thoracic vessels as recipient vessels for reconstruction of the cervicothoracic spine with free vascularized fibula grafts. SUMMARY OF BACKGROUND DATA: The cervicothoracic junction is a difficult region in reconstructive spinal surgery. Although nonvascularized fibula grafts can be used to reconstruct the osseous defect, compared with free vascularized fibula grafts they are biomechanical weaker, incorporate less well, are less resistant to infection, and remodel incomplete in time. However, when using free vascularized bone grafts, the selection of suitable recipient vessels remains one of the most critical decisions. MATERIALS AND METHODS: Four patients who had a primary tumor (3 cases) or a severe progressive kyphotic deformity and progressive neurologic symptoms due to tuberculosis (1 case) were treated by resection and vascularized reconstruction. In 3 patients, a staged anteroposterior en bloc resection of T1-T3 (2 cases) or T1-T2 (1 case) was performed; the ventral reconstruction of the osseous defect consisted of a vascularized fibula graft interposition between C7-T4 (2 cases) or C7-T3 (1 case). In another case, an axial slot was milled through the T1-T2 vertebral bodies to accept an osteotomized vascularized fibular graft. In all cases, a free vascularized fibula graft was used: the vascular anastomosis was performed between the peroneal and the dissected and rerouted internal thoracic vessels. The anterior construction was strengthened by a ventral plate-screw system. RESULTS: The resection-reconstruction procedures, including the dissection, rerouting, and anastomosis between the internal thoracic vessels and the peroneal vessels, were successfully performed. At present, all patients are alive, and there is no evidence of recurrent disease, unchanged, or improved neurologic with a mean follow-up of 28 months. All grafts are well incorporated. CONCLUSIONS.: A combined low anterolateral cervical and midsternal approach or a midline sternotomy allows not only a safe and excellent exposure to the cervicothoracic junction but also to the internal thoracic vessels. The internal thoracic vessels are appropriate donor vessels: its longevity, diameter, length, and rerouting capacity allow vascularized graft reconstruction of vertebral column defects of the low cervical (C6-C7) and/or upper thoracic (T1-T3) region.

Spinal tuberculosis in a 14-year-old immigrant in the Netherlands.

We present a case of Pott's disease, where the patient presented with neurological impairment due to vertebral granulomatous necrosis, needing immediate decompression and later stabilizing and reconstructive orthopaedic surgery, in order to create awareness for TB in general, especially this forgotten form of spinal tuberculosis.

Lumbar body fusion with a bioresorbable cage in a goat model is delayed by the use of a carboxymethylcellulose-stabilized collagenous rhOP-1 device.

The purpose of this study was to evaluate the efficacy of recombinant human osteogenic protein-1 (rhOP-1) with a carboxymethylcellulose-stabilized collagenous carrier as a bone graft substitute for instrumented lumbar spinal fusion in an established goat model. Twenty goats received a resorbable poly-L-lactic acid (PLLA) interbody cage packed with either rhOP-1 and its carrier or autologous bone graft. The carrier material was bovine collagen type-1 stabilized with carboxymethylcellulose. The fusion segments were retrieved at 3 or 6 months postimplantation and evaluated by radiographic and histologic analyses. The rhOP-1 graft substitute, used in combination with the resorbable PLLA cage, showed inferior results as compared to autologous bone graft in the goat lumbar fusion model. Whereas four out of five segments from the autograft group were fused after 6 months, none of the four segments receiving the rhOP-1 graft substitute were fused at this time point. Bone ingrowth into the cage was delayed or absent in the experimental group, whereas all autograft specimens showed advanced bone ingrowth (3 months) or fusion (6 months). We suggest that the fusion process was inhibited, because cells were unable to penetrate the rhOP-1 graft material. This led to delayed bone formation and in some cases inadequate tissue formation.

A conditionally replicating adenovirus with strict selectivity in killing cells expressing epidermal growth factor receptor.

Virotherapy of cancer using oncolytic adenoviruses has shown promise in both preclinical and clinical settings. One important challenge to reach the full therapeutic potential of oncolytic adenoviruses is accomplishing efficient infection of cancer cells and avoiding uptake by normal tissue through tropism modification. Towards this goal, we constructed and characterized an oncolytic adenovirus, carrying mutated capsid proteins to abolish the promiscuous adenovirus native tropism and encoding a bispecific adapter molecule to target the virus to the epidermal growth factor receptor (EGFR). The new virus displayed a highly selective targeting profile, with reduced infection of EGFR-negative cells and efficient killing of EGFR-positive cancer cells including primary EGFR-positive osteosarcoma cells that are refractory to infection by conventional adenoviruses. Our method to modify adenovirus tropism might thus be useful to design new oncolytic adenoviruses for more effective treatment of cancer.

The clinical significance of lumbosacral transitional anomalies.

Lumbosacral transitional vertebrae (LSTV) are common congenital anomalies of the human spine. In LSTV, either the fifth lumbar vertebra may show assimilation to the sacrum (sacralisation), or the first sacral vertebra may show transition to a lumbar configuration (lumbarisation). Although the condition has an incidence of over 12% in the general population, knowledge about the exact clinical implications is still lacking. The association between LSTV and low back pain has been debated since it was first described by Bertolotti almost a century ago. Furthermore, several conflicting studies have been published regarding the association of LSTV with other spinal pathology. There seems to be a relation with early disc degeneration above the LSTV in young patients. However, these differences fade with age as they are masked by other degenerative changes of the spine. From a practical view-point, failure to recognise and to number LSTV during spinal surgery may have serious consequences.

Interobserver reliability of the Mallet score.

The interobserver reliability of the Mallet score for active shoulder function was assessed by three experienced observers in a group of 30 children with an obstetric brachial plexus lesion (mean age 7.1 years, range 4.5-10 years). Interobserver reliability, measured using weighted kappa, was good. Kappa varied between 0.37 and 0.84 and differed between the different aspects of the Mallet score and different pairs of observers. In decreasing order, mean weighted kappa was 0.75 for abduction, 0.73 for hand to neck, 0.67 for hand to spine, 0.6 for external rotation and 0.53 for hand to mouth.

Does bioresorbable cage material influence segment stability in spinal interbody fusion?

To reduce long term complications associated with nonresorbable interbody fusion cages, bioresorbable cages are being developed. We investigated the influence of bioresorbable cage material on segment stability, intervertebral disc height and fusion in vivo using radiostereometric analysis comparing 70/30 poly(L-lactide-co-D,L-lactide) (PLDLLA) cages with titanium cages. Twenty-eight goats were randomized to receive PLDLLA (n = 21) or a titanium control (n = 7) cage at L3-L4. Range of motion for flexion and extension and change in intervertebral disc height were measured before and after surgery and at followup (3, 6, and 12 months). Fusion was graded with a validated radiographic score. Although the PLDLLA cage could not provide the optimal environment for a successful high fusion rate, the range of motion of the PLDLLA segments gradually decreased in time and was similar to the titanium control group at 12 months. In addition the decrease of intervertebral disc height was similar for both PLDLLA (1.4 +/- 0.8 mm) and titanium (1.3 +/- 1.0 mm) specimens. Both results showed a bioresorbable cage does not lead to less decrease of motion or more loss of intervertebral disc height in time compared to titanium. This study therefore supports further development of a bioresorbable cage concept.

Radiographic, histologic, and chemical evaluation of bioresorbable 70/30 poly-L-lactide-CO-D, L-lactide interbody fusion cages in a goat model.

STUDY DESIGN: A study of lumbar interbody fusion using polylactic acid-based bioresorbable fusion cages in a goat model. OBJECTIVE: To evaluate the effect of polylactic acid polymer composition, and internal stabilization on the rate and quality of interbody fusion. SUMMARY OF BACKGROUND DATA: A spinal cage should provide an appropriate biomechanical environment to facilitate interbody fusion. Previous studies have shown that bioresorbable polylactic acid-based cages can provide adequate stability for spinal fusion. However, at present and to our knowledge, the best bioresorbable materials, optimal cage stiffness, and desired period over which the cage should biodegrade are unknown. METHODS: Interbody fusions were performed at L3-L4 level in 35 skeletally mature Dutch milk goats. Titanium and poly-L-lactide-CO-D,L-lactide (PLDLLA) cages were implanted at random as stand-alone cages. In addition, PLDLLA cages were implanted with anterior fixation. The goats were euthanized at 3, 6, or 12 months. Radiographic, magnetic resonance imaging, histologic, and histomorphometric analyses were performed on retrieved segments. Chemical analysis was used to assess degradation of the retrieved PLDLLA cages. Beforehand, chemical and mechanical degradation of the PLDLLA cages were assessed in vitro. RESULTS: At 3 months, bone graft was almost completely remodeled. Endochondral bone formation was observed in all specimens. At 6 months, 50% of the PLDLLA stand-alone cages and 83% of the PLDLLA anterior fixation cages were fused. At 12 months, 38% of the PLDLLA stand-alone and 83% of the titanium cages realized fusion. A very mild and dispersed foreign body reaction was seen in all PLDLLA specimens. E-beam sterilized PLDLLA cages degraded more rapidly in vivo as compared to both, PLDLLA cages in vitro, and ethylene oxide sterilized poly-L-lactic acid cages in vivo. CONCLUSIONS: Within the 3-6-month period, PLDLLA stand-alone cages provided insufficient mechanical stability, which manifested as cracking and deformation of the cages and lower fusion rates. This result implies that within this time, additional stabilization is required; supplemental internal fixation proved sufficient to obtain successful fusion. In all cases, only a mild host response was seen, indicating good biocompatibility.