Evolution of mesoporous bioactive glass scaffold implanted in rat femur based on 45Ca labelling, tracing and histological analysis

Authors

Baiyan Sui, Gaoren Zhong, and Jiao Sun

Abstract

Mesoporous bioactive glass (MBG) as a biodegradable scaffold with a nanostructure has attracted significant attention. However, the in vivo evolution of MBG, which includes in-situ degradation, the local effect induced by degradation and the disposition of degradation products, remains unclear. In this study, we performed in situ labelling and synthesis of MBG scaffold for the first time using 45CaCl2. The obtained 45Ca-MBG scaffolds possessed as mesoporous-macroporous cross-linked structure. These 45Ca-MBG scaffolds were implanted in critical-sized rat femur defects (3×3 mm) for 1 day and for 1, 4, 8 and 12 weeks and analyzed by isotopic quantitative tracing. The results illustrated MBG scaffolds gradually degraded over time and persisted at a local level of approximately 9.63% at week 12. This finding suggests that only a very small amount of MBG-released calcium ions may have been transformed into calcium components of the new bone matrix. The research also confirmed that the active ingredients derived from the degradation of MBG scaffolds could actively regulate the mRNA expression levels of osteoblast-related genes in rat bone marrow-derived mesenchymal stem cells (rBMSCs) and promote bone regeneration in vivo. Moreover, through isotopic tracing of the entire body, 45Ca, which disappeared in situ after implantation, could be detected in the heart, lungs, spleen, kidneys, intestines and brain via the blood and mainly accumulated in distal bone tissue, including the radius and cranium. However, 45Ca radioactivity in the body tissues significantly decreased or disappeared after 12 weeks. Systemic toxicological studies on MBG scaffolds demonstrated the degradation products that spread to major organs did not cause abnormal histopathological changes. The above discoveries comprehensively address crucial issues regarding the application of MBG in vivo, and these findings provide a scientific basis for introducing a material with mesoporous structure into clinical applications.

Link To Article

http://dx.doi.org/10.1021/am4056886

Local microarchitecture affects mechanical properties of deposited extracellular matrix for osteonal regeneration

Authors

M. Pilia, T. Guda, B. Pollot, V. Aguero, M. Appleford

Abstract

Multiple biomimetic approaches have been attempted to accelerate the regeneration of functional bone tissue. While most synthetic scaffolds are designed to mimic the architecture of trabecular bone, in the current study, cortical bone-like extracellular matrix was regenerated in vitro within organized structures. Biphasic calcium phosphate (BCaP) and hydroxyapatite (HAp) scaffolds were developed with longitudinal microchannels (250 μm diameter) that resembled native osteons in cortical bone. BCaP and HAp scaffolds had a compressive strength of 7.61 ± 1.42 and 9.98 ± 0.61 MPa respectively. The constructs were investigated in vitro to evaluate the organization and stiffness of the extracellular matrix (ECM) formed by human fetal osteoblasts (HFObs) cultured inside the microchannels. The ECM deposited on the BCaP scaffolds was found to have a higher micro-hardness (h) (1.93 ± 0.40GPa) than the ECM formed within the HAp microchannels (h = 0.80 ± 0.20GPa) (p < 0.05) or native bone (h = 0.47-0.74GPa). ECM deposition within the microchannels resembled osteoid organization and showed a significant increase in both osteoid area and thickness after 24 days (p < 0.001). These observations indicate that controlled microarchitecture; and specifically cylindrical microchannels; plays a fundamental role in stimulating the appropriate cellular response aimed at recreating organized, cortical bone-like matrix. These findings open the door for researchers to develop a new generation of cortical bone scaffolds that can restore strong, organized bone.

Link to Article

http://dx.doi.org/10.1016/j.msec.2013.10.018

Assessment of epidural versus intradiscal biocompatibility of PEEK implant debris: an in vivo rabbit model

Authors

Nadim J. Hallab, Qi-Bin Bao, Tim Brown

Abstract

Purpose: To understand the relative histopathological effects of PEEK particulate debris when applied within the epidural versus the intervertebral disc space. We hypothesized that due to the avascular nature of the intervertebral disc acting as a barrier to immune cells, the intradiscal response would be less than the epidural response. Methods: The inflammatory effects of clinically relevant doses (3 mg/5-kg rabbit) and sizes (1.15 µm diameter) of PEEK implant debris were assed when placed dry on epidural and intradiscal tissues in an in vivo rabbit model. The size of the particulate was based on wear particulate analysis of wear debris generated from simulator wear testing of PEEK spinal disc arthroplasty devices. Local and systemic gross histology was evaluated at the 3- and 6-month time points. Quantitative immunohistochemistry of local tissues was used to quantify the common inflammatory mediators TNF-α, IL-1β, and IL-6. Results: Both treatments did not alter the normal appearance of the dura mater and vascular structures; however, limited epidural fibrosis was observed. Epidural challenge of PEEK particles resulted in a significant (30 %) increase (p < 0.007) in TNF-α and IL-1β at both 3 and 6 months compared to that of controls, and IL-6 at 6 months (p < 0.0001). Intradiscal challenge of PEEK particles resulted in a significant increase in IL-1β, IL-6 and TNF-α at 6-months post-challenge (p ≤ 0.03). However, overall there were only moderate increases in the relative amount of these cytokines when compared with surgical controls (10–20 %). In contrast, epidural challenge resulted in a 50–100 % increase. Conclusions: The results of this study are similar to past investigations of PEEK, whose results have not been shown to elicit an aggressive immune response. The degree to which these results will translate to the clinical environment remains to be established, but the pattern of subtle elevations in inflammatory cytokines indicated both a mild persistence of responses to PEEK debris, and that intradiscal implant debris will likely result in less inflammation than epidural implant debris.

Link to Article

http://dx.doi.org/10.1007/s00586-013-2904-4

Production and repair of implant-induced microdamage in the cortical bone of goats after long-term estrogen deficiency

Authors

Z. Yu, G. Wang, T. Tang, L. Fu, X. Yu, L. Cao, Z. Zhu, K. Dai, S. Qiu

Abstract

Summary: By using an ovariectomized goat model, we found that estrogen depletion decreases bone quality and makes it susceptible to screw-induced mechanical microdamage. Both diffuse microdamage and linear cracks accumulated up to 3 weeks after screw implantation, and the microdamage was repaired gradually after 4–8 months. Introduction: The aim of this study was to observe the effect of long-term estrogen deficiency on the creation and repair of microdamage in cortical bone adjacent to bone screw. Methods: Cortical bone screws were placed in the tibial diaphyses 28 months after ovariectomy (OVX) or sham operation (Sham-Op) in female goats. The goats were euthanized at 0 day, 21 days, 4 months, and 8 months after screw implantation. Microdamage morphology and repair were examined in peri-screw bone using histomorphometric method, and the nanomechanical properties of peri-screw bone were examined with nanoindentation testing. Results: Tibiae from ovariectomized goats in which screws had been placed had significantly higher levels of diffuse microdamage and significantly more linear cracks than those from sham goats, and the diffuse microdamage was more obvious than linear cracks in the region adjacent to the implant. Both diffuse microdamage and linear cracks accumulated up to day 21 and then gradually repaired at 4 and 8 months after surgery. The trend for bone remodeling in each group was consistent with changes in the level of microdamage. Nanoindentation testing showed that both elastic modulus and hardness in peri-screw bone were significantly decreased in OVX group compared to Sham-Op group. The hardness and elastic modulus also showed a downward trend up to 4 months after screw implantation and then exhibited some recovery after 8 months. Conclusions: Estrogen depletion decreases bone quality and makes it vulnerable to screw-induced mechanical damage, which may compromise the initial stability of an orthopedic implant.

Link to Article

http://dx.doi.org/10.1007/s00198-013-2496-1

Effect of maxillomandibular fixation on condylar growth in juvenile Macaca mulatta: a cephalometric and histologic study

Authors

Goran Isacsson, David S. Carlson, James A. McNamara, Jr. and Annika M. Isberg

Abstract

The effect of maxillomandibular fixation on the growth of the mandibular condyle was studied in eight control and eight experimental male juvenile monkeys. All animals had metallic implants placed throughout the craniofacial complex in order to facilitate cephalometric analysis of growth-related changes in the maxillomandibular complex during jaw immobilization. Every 3, 6, 12, and 24 wk after insertion of the appliance two experimental animals were killed for histologic analysis. Cephalometric analysis indicated no major deviation from normal maxillary or mandibular growth in the experimental animals. The condylar growth in the experimental animals was comparable with that of the controls. Histologic analysis indicated that the articular connective tissue in experimental joints remained the same thickness as in the controls. On the postero-superior aspect of the condyle, the thickness of the prechondroblastic-chondroblastic cell layer was reduced by 70-80% in the experimental animals. On the posterior aspect this cell layer was not visible after 12 wk of fixation, but was replaced by a periosteum-like, cell-rich tissue which appeared to be active in appositional formation of cancellous bone. These results indicate that long-term maxillomandibular fixation does not cause major alterations in the growth of condyle or the entire mandible despite a profound decrease of the prechondroblastic-chondroblastic cell layer in the postero-superior and posterior regions of the condyle. The growth is probably due to a compensatory appositional bone formation along the surface of the condyle. It is also concluded that jaw mobility is not a prerequisite for normal maxillary or mandibular growth.

Link to Article

http://prod.umdentistry.com/sites/default/files/departments/opd/090.pdf

Recombinant human bone morphogenetic protein-2 stimulates bone formation during interfrontal suture expansion in rabbits

Authors

Sean Shih-Yao Liu, Haisong Xu, Jun Sun, Elias Kontogiorgos, Patrick R. Whittington, Kenner G. Misner, Hee-Moon Kyung, Peter H. Buschang, Lynne A. Opperman

Abstract

Introduction: Suture expansion stimulates bone growth to correct craniofacial deficiencies but has a high potential of treatment relapse. The objective of this study was to investigate whether there is a dose-dependent relationship between the recombinant human bone morphogenetic protein-2 (rhBMP-2) and bone formation during suture expansion. Methods: Fifty 6-week-old male New Zealand white rabbits were randomly assigned to 5 groups to receive 0 (control), 0.01, 0.025, 0.1, or 0.4 mg/mL of rhBMP-2 delivered by absorbable collagen sponge placed over the interfrontal suture. The suture was expanded for 33 days by 200 g of constant force via a spring anchored with 2 miniscrew implants. Distance of suture expansion, suture volume, and cross-sectional area after expansion were measured using radiographs with bone markers and microcomputed tomography. Suture widths and mineralization appositional rates were calculated based on the widths between bone labels under an epifluorescent microscope. Software (Multilevel Win 2.0; University of Bristol, Bristol, United Kingdom) was used to model distance of suture expansion over time as polynomials to compare group differences. Wilcoxon signed rank tests were performed to compare the suture volume and cross-sectional area, mineral apposition rate, and suture width between groups. The significance level was set at P = 0.05. Results: Whereas the sutures were expanded in all groups, sutures were expanded by significantly greater amounts in the control and the 0.01 mg/mL groups without fusing the sutures than in the 0.025, 0.1, and 0.4 mg/mL groups with fusing sutures. Compared with the controls, the 0.01 mg/mL group showed significantly lower suture volumes, cross-sectional areas, and suture widths after expansion. The mineral apposition rate was significantly higher in the 0.01 mg/mL group than in the controls from days 10 to 30. Conclusions: The 0.01 mg/mL dose of rhBMP-2 delivered by absorbable collagen sponge can stimulate bone formation at the bony edges of the suture during suture expansion; however, higher concentrations cause suture fusion. With an appropriate concentration, rhBMP-2 might facilitate suture expansion for clinical uses.

Link to Article

http://dx.doi.org/10.1016/j.ajodo.2013.03.017