A New Method for Creating Impact-Induced Intra-Articular Fractures in a Rabbit Model Induces Severe Post-Traumatic Osteoarthritis.

OBJECTIVES: The objective of this work was to develop a model of intra-articular fracture (IAF) in a rabbit and document the speed and severity of degenerative joint changes after fracture fixation. METHODS: With Institutional Animal Care & Use Committee approval, impact-induced IAFs were created in the distal tibia of 16 New Zealand White rabbits. Fractures were fixed with a plate and screws. Pain and function were monitored at regular postoperative intervals with limb loading analysis. Twelve or 26 weeks after fracture, animals were euthanized for histological assessment of cartilage degeneration and micro-computed tomography analysis of bone histomorphometry. RESULTS: Eleven animals successfully completed the study. Maximum foot force in the fractured limb was 41% ± 21% lower than preoperative values ( P = 0.006) 12 weeks after fracture and remained 25% ± 13% lower ( P = 0.081) after 26 weeks. Cortical bone mineral density in micro-computed tomography images was 34% ± 13% lower 12 weeks after fracture ( P < 0.001) and remained (42% ± 8%) lower 26 weeks after fracture ( P < 0.001). Twelve weeks after fracture, Mankin scores of cartilage degeneration were significantly higher in the medial talus ( P = 0.007), lateral talus ( P < 0.001), medial tibia ( P = 0.017), and lateral tibia ( P = 0.002) of the fractured limb compared with the uninjured contralateral limb. Average Mankin scores in the talus increased from 12 to 26 weeks (5.9 ± 0.9 to 9.4 ± 0.4; P < 0.001 lateral; 5.4 ± 1.8 to 7.8 ± 2.0; P = 0.043 medial), indicating substantial and progressive joint degeneration. CONCLUSIONS: The ankle joint of the New Zealand White rabbit provides the smallest available model of impact-induced IAF that can be treated with clinically relevant techniques and replicates key features of healing and degeneration found in human patients.

Intra-Articular Adeno-Associated Virus-Mediated Proteoglycan 4 Gene Therapy for Preventing Posttraumatic Osteoarthritis.

Lubricin, a glycoprotein encoded by the proteoglycan 4 (PRG4) gene, is an essential boundary lubricant that reduces friction between articular cartilage surfaces. The loss of lubricin subsequent to joint injury plays a role in the pathogenesis of posttraumatic osteoarthritis. In this study, we describe the development and evaluation of an adeno-associated virus (AAV)-based PRG4 gene therapy intended to restore lubricin in injured joints. The green fluorescent protein (GFP) gene was inserted the PRG4 gene to facilitate tracing the distribution of the transgene product (AAV-PRG4-GFP) in vivo. Transduction efficiency of AAV-PRG4-GFP was evaluated in joint cells, and the conditioned medium containing secreted PRG4-GFP was used for shear loading/friction and viability tests. In vivo transduction of joint tissues following intra-articular injection of AAV-PRG4-GFP was confirmed in the mouse stifle joint in a surgical model of destabilization of the medial meniscus (DMM), and chondroprotective activity was tested in a rabbit anterior cruciate ligament transection (ACLT) model. In vitro studies showed that PRG4-GFP has lubricin-like cartilage-binding and antifriction properties. Significant cytoprotective effects were seen when cartilage was soaked in PRG4-GFP before cyclic shear loading (n = 3). Polymerase chain reaction and confocal microscopy confirmed the presence of PRG4-GFP DNA and protein, respectively, in a mouse DMM (n = 3 per group). In the rabbit ACLT model, AAV-PRG4-GFP gene therapy enhanced lubricin expression (p = 0.001 vs. AAV-GFP: n = 7-14) and protected the cartilage from degeneration (p = 0.014 vs. AAV-GFP: n = 9-10) when treatments were administered immediately postoperation, but efficacy was lost when treatment was delayed for 2 weeks. AAV-PRG4-GFP gene therapy protected cartilage from degeneration in a rabbit ACLT model; however, data from the ACLT model suggest that early intervention is essential for efficacy.

Electrospun PLGA and ß-TCP (Rebossis-85) in a Lapine Posterolateral Fusion Model.

Background: Calcium phosphate materials have been employed clinically as bone void fillers for several decades. These materials are most often provided in the form of small, porous granules that can be packed to fill the wide variety of size and shape of bony defects encountered. ReBOSSIS-85 (RB-85) is a synthetic bioresorbable bone void filler for the repair of bone defects with handling characteristics of glass wool-like (or cotton ball-like). The objective of this study is to evaluate the in vivo performance of RB-85 (test material), compared to a commercially available bone void filler, Mastergraft Putty (predicate material), when combined with bone marrow aspirate and iliac crest autograft, in an established posterolateral spine fusion rabbit model. Methods: One hundred fifty skeletally mature rabbits had a single level posterolateral fusion performed. Rabbits were implanted with iliac crest bone graft (ICBG), Mastergraft Putty™ plus ICBG, or one of 4 masses of ReBOSSIS-85 (0.2, 0.3, 0.45, or 0.6 g) plus ICBG. Plain films were taken weekly until euthanasia. Following euthanasia at 4, 8, and 12 weeks, the lumbar spine were tested by manual palpation. Spinal columns in the 12 week group were also subjected to non-destructive flexibility testing. MicroCT and histology were performed on a subset of each implant group at each euthanasia period. Results: Radiographic scoring of the fusion sites indicated a normal healing response in all test groups. Bilateral radiographic fusion rates for all test groups were 0% at 4 weeks; ICBG 43%, Mastergraft Putty 50%, RB-85-0.2g 0%, RB-85-0.3g 13%, RB-85-0.45g 38%, and RB-85-0.6g 63% at 8 weeks; and ICBG 50%, Mastergraft Putty 50%, RB-85-0.2g 0%, RB-85-0.3g 25%, RB-85-0.45g 36%, and RB-85-0.6g 50% at 12 weeks.Spine fusion was assessed by manual palpation of the treated motion segments. At 12 weeks, ICBG, MGP, and RB-85-0.6g were fused mechanically in at least 50% of the rabbits. All groups demonstrated significantly less range of motion in both flexion/extension, lateral bending, and axial rotation compared to normal unfused controls.Histopathology analysis of the fusion masses, in all test groups, indicated an expected normal response of mild inflammation with macrophage and multinucleated giant cell response to the graft material at 4 weeks and resolving by 12 weeks. Regardless of test article, new bone formation and graft resorption increased from 4 to 12 weeks post-op. Conclusions: This animal study has demonstrated the biocompatibility and normal healing features associated with the ReBOSSIS-85 bone graft (test material) when combined with autograft as an extender. ReBOSSIS-85 was more effective when a larger mass of test article was used in this study. Clinical Relevance: ReBOSSIS-85 can be used as an extender negating the need for large amounts of local or iliac crest bone in posterolateral fusions.

The Effect of Pulsed Electromagnetic Field and Combined Magnetic Field Exposure Time on Healing of a Rabbit Tibial Osteotomy.

Background: This study compares effectiveness of two commercially available signals, Pulsed Electromagnetic Field (PEMF) and Combined Magnetic Field (CMF) clinical signals, to stimulate bone healing in rabbit tibial osteotomies. Methods: One millimeter osteotomies in New Zealand White rabbits, stabilized with external fixators, were exposed daily to either signal for 30 minutes, three or six hours. Osteotomized sham controls received no signal exposure. Analyses of torsional strength, periosteal callus area and fracture healing stage demonstrated dose responses to increasing daily exposures to both signals. Results: By 14 days torsional strength increased over shams in the three and six hour-treated groups, significant only for the six hour groups (p<0.05). By 21 days both three and six hour-treated groups were significantly stronger than shams (p<0.05, p<0.005) and the PEMF 30 minute treated group also showed significance (p<0.05). PEMF versus CMF-treated groups were not different at any exposure time. Conclusions: Both CMF and PEMF signals were most effective in this model when used for six hours per day. Clinical Relevance: In this model we demonstrate that though both PEMF and CMF are "bioactive" and promote healing at shorter and longer exposure dosages, there exists an "optimal" threshold effect of 6 hours/day electromagnetic wave stimulation for bone healing.

Targeting mitochondrial responses to intra-articular fracture to prevent posttraumatic osteoarthritis.

We tested whether inhibiting mechanically responsive articular chondrocyte mitochondria after severe traumatic injury and preventing oxidative damage represent a viable paradigm for posttraumatic osteoarthritis (PTOA) prevention. We used a porcine hock intra-articular fracture (IAF) model well suited to human-like surgical techniques and with excellent anatomic similarities to human ankles. After IAF, amobarbital or N-acetylcysteine (NAC) was injected to inhibit chondrocyte electron transport or downstream oxidative stress, respectively. Effects were confirmed via spectrophotometric enzyme assays or glutathione/glutathione disulfide assays and immunohistochemical measures of oxidative stress. Amobarbital or NAC delivered after IAF provided substantial protection against PTOA at 6 months, including maintenance of proteoglycan content, decreased histological disease scores, and normalized chondrocyte metabolic function. These data support the therapeutic potential of targeting chondrocyte metabolism after injury and suggest a strong role for mitochondria in mediating PTOA.

Influence of 45S5 Bioactive Glass in A Standard Calcium Phosphate Collagen Bone Graft Substitute on the Posterolateral Fusion of Rabbit Spine.

INTRODUCTION: Spinal fusion surgery is an effective but costly treatment for select spinal pathology. Historically iliac crest bone graft (ICBG) has remained the gold standard for achieving successful arthrodesis. Given well-established morbidity autograft harvest, multiple bone graft replacements, void fillers, and extenders have been developed. The objective of this study was to evaluate the in vivo efficacy and safety of two mineralized collagen bone void filler materials similar in composition. Both bone void fillers were composed of hydroxyapatite (HA), tricalcium phosphate (TCP) and bovine collagen. The first test article (Bi-Ostetic bioactive glass foam or "45S5") also contained 45S5 bioactive glass particles while the second test article (Formagraft or "FG") did not. 45S5 and FG were combined with bone marrow aspirate and iliac crest autograft and compared to ICBG in an established posterolateral spine fusion rabbit model. MATERIALS AND METHODS: Sixty-nine mature New Zealand White rabbits were divided into 3 test cohorts: ICBG, 45S5, and FG. A Posterolateral fusion model previous validated was utilized to assess fusion efficacy. The test groups were evaluated for spine fusion rate, new bone formation, graft resorption and inflammatory response using radiographic, µCT, biomechanical and histological endpoints at 4, 8 and 12 weeks following implantation. RESULTS: There were 4 clinical complications unrelated to the graft materials and were evenly split between groups (ICBG graft harvest complications; hind limb mobility, chronic pain) and were euthanized. These omissions did not affect the overall outcome of the study. Radiographic scoring of the fusion sites indicated a normal healing response in all test groups, with no adverse reactions and similar progressions of new bone formation observed over time. All groups demonstrated significantly less range of motion in both flexion/extension and lateral bending compared to normal not-fused controls, which supports fusion results observed in the other endpoints. Fusion occurred earlier in the 45S5 group: ICBG 0%, FG 0%, and 45S5 20% at 4 weeks; ICBG 43%, FG 38%, and 45S5 50% at 8 weeks; and ICBG 50%, FG 56%, and 45S5 56% at 12 weeks. Histopathology analysis of the fusion masses, from each test article and time point, indicated an expected normal response for resorbable calcium phosphate (HA/TCP) and collagen graft material. Mild inflammation with macrophage and multinucleated giant cell response to the graft material was evident in all test groups. DISCUSSION: This study has confirmed the biocompatibility, safety, efficacy and bone healing characteristics of the HA-TCP collagen (with or without 45S5 bioactive glass) composites. The results show that the 3 test groups had equivalent long-term fusion performance and outcome at 12 weeks. However, the presence of 45S5 bioactive glass seemed to accelerate the fusion process as evidenced by the higher fusion rates at 4 and 8 weeks for the HA-TCP-collagen composite containing bioactive glass particles. The results also demonstrate that the HA-TCP-45S5 bioactive glass-collagen composite used as an extender closely mirrors the healing characteristics (i.e. amount and quality of bone) of the 100% autograft group.

Comparison of Two Synthetic Bone Graft Products in a Rabbit Posterolateral Fusion Model.

BACKGROUND: The drawbacks of iliac crest autograft as graft material for spine fusion are well reported. Despite continued modifications to improve bone healing capacity, the efficacy of synthetic graft materials as stand-alone replacements remains uncertain. The rabbit posterolateral fusion model is an established environment for testing of fusion concepts. It offers the opportunity to obtain radiographic, biomechanical and histological data on novel fusion materials. The objective of this study was to compare the spine fusion capability of two synthetic bone graft products in an established rabbit posterolateral spine fusion (PLF) model: Signafuse® Bioactive Bone Graft Putty and Actifuse® ABX. METHODS: Bilateral intertransverse spine fusion was performed at the L5-L6 transverse processes (TPs) of New Zealand White rabbits using either Signafuse or Actifuse ABX as the bone graft material. Bone remodeling and spine fusion were assessed at 6 and 12 weeks using radiographic, biomechanical and histological endpoints. RESULTS: Fusion rate by manual palpation at 6 weeks was greater for Signafuse (33%) compared to Actifuse ABX (0%), and equivalent in both groups at 12 weeks (50%). Biomechanical fusion rate based on flexion-extension data was 80% in Signafuse group and 44% for Actifuse ABX. Histology revealed a normal healing response in both groups. MicroCT and histomorphometric data at 6 weeks showed greater new bone formation in the Signafuse group compared to Actifuse ABX (p <0.05), with no differences detected at 12 weeks. Histological fusion scores were greater in the Signafuse group at 6 and 12 weeks, indicated by higher degree structural remodeling and tendency towards complete bridging of the fusion bed compared to the Actifuse ABX group. CONCLUSION: Confirmed by several metrics, Signafuse outperformed Actifuse ABX as a standalone synthetic bone graft in an established PLF model, demonstrating greater rates of bone remodeling and spine fusion. The combination of 45S5 bioactive glass and biphasic HA/ßTCP granules of Signafuse appear to provide greater bone healing capability in comparison to the 0.8% silicate-substituted hydroxyapatite material of Actifuse ABX.

Assessment of SiCaP-30 in a Rabbit Posterolateral Fusion Model with Concurrent Chemotherapy.

Chemotherapy derivatives of the rabbit posterolateral fusion model are considered a challenging environment in which to test bone graft materials. The purpose of this study was to determine the performance characteristics of SiCaP-30 as a bone graft substitute relative to autograft (iliac crest bone graft [ICBG]), Actifuse ABX and ß-Tricalcium Phosphate-Bioactive Glass-Type I Collagen (ßTCP-BG) in a rabbit posterolateral spine fusion model with concurrent chemotherapy treatment This was a randomized, controlled study in a laboratory setting with blinded assessment of fusion by manual palpation and flexibility testing. Sixty rabbits were entered into the study with 45 used for analysis. Chemotherapeutic agents, doxorubicin and cis-platin (2.5 mg/kg), were administered one week prior to surgery, and one, two and three weeks post surgery. Bilateral posterolateral lumbar intertransverse process fusions were performed at L5-L6. The lateral two thirds of the transverse processes were decorticated and covered with 3cc/side of one of the following graft materials: autologous ICBG, Actifuse ABX (ApaTech Ltd, UK), Vitoss BA (Orthovita, USA) or SiCaP-30 (ApaTech Ltd., UK). Animals were euthanized 12 weeks post surgery. The ICBG group had a 45% (5/11) manual palpation fusion rate and correlated with motion analysis fusion results of 36% (4/11). The Actifuse ABX group had a 33% (4/12) manual palpation fusion rate and a motion analysis fusion rate of 25% (3/12). No motion segments in the Vitoss BA group (0/11) showed any signs of fusion. The SiCaP-30 group demonstrated a statistically higher manual palpation and motion analysis fusion rate of 82% (9/11; p<0.05) and produced superior bone formation compared with Actifuse ABX and ßTCP-BG.

Evaluation of a novel silicate substituted hydroxyapatite bone graft substitute in a rabbit posterolateral fusion model.

STUDY DESIGN/SETTING: Randomized, controlled study in a laboratory setting. Blinded observations/assessment of study outcomes. OBJECTIVE: The purpose of this study is to determine the performance characteristics of a novel silicate-substituted hydroxyapatite bone graft substitute (BGS), SiCaP EP (Baxter Healthcare/ ApaTech, Elstree, UK), in a stand-alone mode, a stand-alone with bone marrow aspirate (BMA) mode, and an extender mode with iliac crest autograft (ICBG) in a rabbit posterolateral spine fusion model. The investigational BGS is compared to a standard iliac crest autograft (ICBG) control. SUMMARY OF BACKGROUND DATA: The rabbit posterolateral fusion model is an established environment for testing of fusion efficacy. It offers the opportunity to obtain radiographic, histological, and biomechanical data on novel bone graft substitutes. METHODS: One hundred and twenty rabbits were entered into the study with 116 used for analysis. Bilateral posterolateral lumbar intertransverse fusions were performed at L5-L6. The lateral two thirds of the transverse processes were decorti cated and covered with graft material in the following five groups: ICBG, SiCaP EP stand-alone, SiCaP EP with BMA (1:0.5 by volume), and SiCaP EP with ICBG (1:3 by volume). Rabbits were necropsied at 4, 8, and 12-week time points and fusion rate, quantity, and quality was evaluated based on manual palpation, mechanical stiffness testing, pqCT, and histological assessment. RESULTS: SiCaP EP, ICBG+SiCaP EP (3:1), and SiCaP EP+BMA (1:0.5) compare favorably to iliac crest autologous bone by multiple metrics in this rabbit posterolateral fusion model. Fusion efficacy via manual palpation and mechanical stiffness testing metrics indicate that all SiCaP EP groups had similar group-to-group performance, and were not significantly different than the ICBG control at each time period evaluated. CONCLUSIONS: In this commonly used rabbit posterolateral fusion model, SiCaP EP utilized as a stand-alone, as a stand-alone with BMA, and as an autograft (ICBG) extender produces results that are clinically and radiographically similar to ICBG.

Assessment of Mastergraft(®) strip with bone marrow aspirate as a graft extender in a rabbit posterolateral fusion model.

STUDY DESIGN/SETTING: Randomized, controlled study in a laboratory setting. Blinded observations/assessment of study outcomes. OBJECTIVE: The Purpose of this study is to determine the performance characteristics of Mastergraft(®) Strip with bone marrow aspirate (BMA) as a bone graft extender in a rabbit posterolateral spine fusion model. SUMMARY OF BACKGROUND DATA: The rabbit posterolateral fusion model is an established environment for testing of fusion concepts. It offers the opportunity to obtain radiographic, histological, and biomechanical data on novel fusion materials. METHODS: Thirty six rabbits were entered into the study with 34 used for analysis. Bilateral posterolateral lumbar intertransverse fusions were performed at L5-L6. the lateral two thirds of the transverse processes were decorticated and covered with graft material: autograft only (2.5 - 3.0 cc/side), 75% Mastergraft(®) Strip + 5.0 cc BMA / 25% autograft (3.0 cc total per side), or 50% Mastergraft(®) Strip + 5.0cc BMA and 50% autograft (3.0 cc total per side). Animals were humanely euthanized at 8 weeks post surgery. RESULTS: The autograft group had a 60% radiographic fusion rate (6/10) and a manual palpation fusion rate of 50% (5/10). the 50% Mastergraft(®) Strip group had a 75% radiographic and manual palpation fusion rate (9/12). the 75% Mastergraft(®) Strip group demonstrated a 58% (7/12) radiographic and manual palpation fusion rate. Histologically, no adverse inflammatory reactions of significant size were present. The two Mastergraft(®) Strip groups demonstrated a tendency towards more bone development across the fusion bed. CONCLUSIONS: In this commonly used rabbit posterolateral fusion model, Mastergraft(®) Strip with BMA in an autograft extender mode produces biomechanical and radiographic results similar to autograft fusion alone.

Assessment of MASTERGRAFT PUTTY as a graft extender in a rabbit posterolateral fusion model.

STUDY DESIGN: Randomized, controlled study in a laboratory setting. Blinded observations/assessment of study outcomes. OBJECTIVE: The purpose of this study was to determine the performance characteristics of MASTERGRAFT PUTTY as a bone graft extender in a rabbit posterolateral spine fusion model. SUMMARY OF BACKGROUND DATA: The rabbit posterolateral fusion model is an established environment for testing of fusion concepts. It offers the opportunity to obtain radiographical, histological, and biomechanical data on novel fusion materials. METHODS: Thirty-six rabbits were entered into the study with 30 used for analysis. Bilateral posterolateral lumbar intertransverse fusions were performed at L5-L6. The lateral two-thirds of the transverse processes were decorticated and covered with graft material: autograft only (2.5-3.0 cc per side), 25% MASTERGRAFT PUTTY/75% autograft (3.0 cc total per side), or 50% MASTERGRAFT PUTTY and 50% autograft (3.0 cc total per side). Animals were humanely killed at 8 weeks postsurgery. RESULTS: The autograft group had a 63% radiographical fusion rate (5 of 8) and correlated with manual palpation results (63%). The 25% MASTERGRAFT PUTTY group had a 73% radiographical fusion rate (8 of 11) and a manual palpation fusion rate of 64%. The 50% MASTERGRAFT PUTTY group demonstrated a 91% (10 of 11) radiographical fusion rate and 73% manual palpation fusion rate. Histologically, no inflammatory reactions were evident regardless of implant. The 2 MASTERGRAFT PUTTY groups had new bone in direct apposition to the MASTERGRAFT ceramic granules. CONCLUSION: In this commonly used rabbit posterolateral fusion model, MASTERGRAFT PUTTY in an autograft extender mode produces clinically and radiographically similar results to autograft fusion alone.

B2A peptide on ceramic granules enhance posterolateral spinal fusion in rabbits compared with autograft.

STUDY DESIGN: Six groups of 10 animals underwent single level, uninstrumented posterolateral lumbar fusions. Graft sites were implanted with autologous bone, autologous bone plus B2A coated granules with concentrations of 0-, 50-, 100-, or 300 microg/mL, or no graft material. Explanted motion segments were analyzed by Faxitron radiographs, computerized tomography (CT), manual palpation, and histology. OBJECTIVE: The synthetic peptide B2A2-K-NS (B2A) was evaluated as a novel agent for augmenting spinal fusion in a posterolateral, noninstrumented rabbit lumbar spine fusion model. SUMMARY OF BACKGROUND DATA: There have been many efforts to increase the rate of posterolateral spinal fusion while, at the same time minimizing, use of autologous bone with its inherent harvest morbidity. METHODS: B2A coated ceramic granules (0-, 50-, 100-, and 300 microg/mL) were mixed 1:1 with autogenous iliac crest bone and implanted. Autogenous bone alone was used as a positive control. Fusion was assessed at 6 weeks via radiographs and manual palpation. These results were confirmed with histology and CT. RESULTS: Fusion results from palpation and radiographic evaluations were similar. CT and histology confirmed bridging bone across the transverse processes for fused spines. The highest fusion rates were observed in the 100 mug B2A/mL group-89% in comparison to 33% for uncoated granules (0 microg B2A/mL) and 63% for autograft alone. These differences were statistically significant. CONCLUSION: All investigated B2A concentrations demonstrated increased fusion rates. Fusion masses resulting from the implantation of 100 mug B2A/mL granules demonstrated new woven bone: fused to the transverse processes, within granule pores, bridging bone across the transverse processes, and bridging residual bone graft and granules. It was concluded that each investigated concentration of B2A coated granules in a 1:1 mixture with autograft increased fusion rates in comparison to controls in this rabbit model.

Effects of direct current electrical stimulation on gene expression of osteopromotive factors in a posterolateral spinal fusion model.

STUDY DESIGN: An in vivo model was used to determine levels of mRNA expression in response to direct current (DC) electrical stimulation in a rabbit posterolateral fusion model. OBJECTIVES: This study tested the possibility that DC stimulation at the surgery site would increase expression of genes related to bone formation relative to expression in autograft alone. SUMMARY OF BACKGROUND DATA: DC electrical stimulation as an adjunct treatment in spinal surgery has shown increased fusion rates when compared with autograft alone, yet the biology of such treatment is not fully understood. METHODS: Thirty New Zealand White rabbits were entered into the study. A posterolateral, intertransverse process fusion was performed bilaterally at L4-L5, with autogenous bone graft. An implantable DC stimulator was placed across the decorticated transverse processes before placement of autograft. Animals were killed at 3, 7, 14, 21, and 28 days. mRNA levels of BMP-2, 4, 6, 7, VEGF, FGF-2, TGF-beta, ALK-2, and ALK-3 were evaluated with real-time RT-PCR. RESULTS: mRNA expression was significantly higher in the DC stimulated animals versus the control animals for several of the genes studied. In particular, levels of mRNA were elevated for BMP-2, BMP-6, and BMP-7. CONCLUSIONS: This study shows for the first time that DC stimulation results in a sustained increase of multiple osteogenic genes, suggesting that the biologic mechanism for the DC-induced increase in the rate and extent of bone formation observed clinically may be mediated by the up-regulation of these osteoinductive factors.

Cellular interactions and bone healing responses to a novel porous tricalcium phosphate bone graft material.

The use of a porous tricalcium phosphate bone void filler (Cellplex TCP, Wright Medical Technology, Inc, Arlington, Tenn) as an alternative to autograft in bone grafting was studied in benchtop, in vitro cell culture, and in vivo preclinical studies. The experimental design included material property quantification, scaffold seeding with mesenchymal stem cells, and implantation in a rabbit segmental defect model. Measured material properties denoted appropriate composition, porosity, and strengths as compared to the literature. Fluid uptake studies and mesenchymal stem cell affinity revealed the scaffold's capabilities as a suitable host for osteoprogenitor cells. In a 1-cm rabbit diaphyseal segmental defect stabilized with an external fixator, tricalcium phosphate was compared to intact autograft, crushed autograft, and open defects. Torsional strengths and stiffnesses of tricalcium phosphate-treated tibia were greater than or equivalent to both intact and crushed autograft controls. Tricalcium phosphate pores exhibited complete bony infiltration histologically. Collectively, the tricalcium phosphate material properties, cell seeding capabilities, and in vivo biological responses give evidence of this implant's functionality as a potential alternative for autograft.