scholarly journals Bone Regeneration in Load-Bearing Segmental Defects, Guided by Biomorphic, Hierarchically Structured Apatitic Scaffold

Author(s):  
Elizaveta Kon ◽  
Francesca Salamanna ◽  
Giuseppe Filardo ◽  
Berardo Di Matteo ◽  
Nogah Shabshin ◽  
...  

The regeneration of load-bearing segmental bone defects remains a significant clinical problem in orthopedics, mainly due to the lack of scaffolds with composition and 3D porous structure effective in guiding and sustaining new bone formation and vascularization in large bone defects. In the present study, biomorphic calcium phosphate bone scaffolds (GreenBone™) featuring osteon-mimicking, hierarchically organized, 3D porous structure and lamellar nano-architecture were implanted in a critical cortical defect in sheep and compared with allograft. Two different types of scaffolds were tested: one made of ion-doped hydroxyapatite/β-tricalcium-phosphate (GB-1) and other made of undoped hydroxyapatite only (GB-2). X-ray diffraction patterns of GB-1 and GB-2 confirmed that both scaffolds were made of hydroxyapatite, with a minor amount of β-TCP in GB-1. The chemical composition analysis, obtained by ICP-OES spectrometer, highlighted the carbonation extent and the presence of small amounts of Mg and Sr as doping ions in GB-1. SEM micrographs showed the channel-like wide open porosity of the biomorphic scaffolds and the typical architecture of internal channel walls, characterized by a cell structure mimicking the natural parenchyma of the rattan wood used as a template for the scaffold fabrication. Both GB-1 and GB-2 scaffolds show very similar porosity extent and 3D organization, as also revealed by mercury intrusion porosimetry. Comparing the two scaffolds, GB-1 showed slightly higher fracture strength, as well as improved stability at the stress plateau. In comparison to allograft, at the follow-up time of 6 months, both GB-1 and GB-2 scaffolds showed higher new bone formation and quality of regenerated bone (trabecular thickness, number, and separation). In addition, higher osteoid surface (OS/BS), osteoid thickness (OS.Th), osteoblast surface (Ob.S/BS), vessels/microvessels numbers, as well as substantial osteoclast-mediated implant resorption were observed. The highest values in OS.Th and Ob. S/BS parameters were found in GB-1 scaffold. Finally, Bone Mineralization Index of new bone within scaffolds, as determined by micro-indentation, showed a significantly higher microhardness for GB-1 scaffold in comparison to GB-2. These findings suggested that the biomorphic calcium phosphate scaffolds were able to promote regeneration of load-bearing segmental bone defects in a clinically relevant scenario, which still represents one of the greatest challenges in orthopedics nowadays.

Author(s):  
Fei Xing ◽  
Lang Li ◽  
Jiachen Sun ◽  
Guoming Liu ◽  
Xin Duan ◽  
...  

Abstract Background Segmental bone defects caused by trauma, tumors, or infection are a serious challenge for orthopedists in the world. Recent developments in tissue engineering have provided a new treatment for segmental bone defects. Urine-derived stem cells (USCs) can be obtained noninvasively and might be a new kind of seed cells used in bone tissue regeneration. Therefore, the first aim of the present study was to investigate the biological characteristics of USCs. The second aim of the present study was to study the osteogenic effect of surface mineralized biphasic calcium phosphate ceramics (BCPs) loaded with USCs in vitro and in vivo. Methods We isolated USCs from the urine of healthy adult donors and evaluated the biological characteristics of USCs in vitro. We mineralized the surface of BCPs by simulated body fluid (SBF). Cell adhesion and proliferation of USCs on the surface mineralized BCPs were evaluated. Osteogenic proteins and genes of USCs on the surface mineralized BCPs were texted by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR) assay. Critical-sized segmental bone defects model in New Zealand white rabbits were established and randomly divided into 4 groups (surface mineralized BCPs loaded with USCs, BCPs loaded with USCs, surface mineralized BCPs, and BCPs) based on the implant they received. The therapeutic efficacy of the scaffolds in a large bone defect at post-implantation was evaluated by imaging and histological examination. Results USCs isolated in our study expressed stem cell-specific phenotypes and had a stable proliferative capacity and multipotential differentiation capability. Surface mineralized BCPs promoted osteogenic proteins and genes expression of USCs without affecting the proliferation of USCs. After 10 weeks, the amount of new bone formation was the highest in the group of surface mineralized BCPs loaded with USCs. Conclusion USCs, from non-invasive sources, have good application prospects in the field of bone tissue engineering. Surface mineralized BCPs can significantly enhance osteogenic potential of USCs without changing biological characteristics of BCPs. Surface mineralized BCPs loaded with USCs are effective in repairing of critical-sized segmental bone defects in rabbits.


2020 ◽  
Vol 209 (2–3) ◽  
pp. 128-143
Author(s):  
Qing Yu ◽  
Robin DiFeo Jacquet ◽  
William J. Landis

Delayed-union or non-union between a host bone and a graft is problematic in clinical treatment of segmental bone defects in orthopedic cases. Based on a preliminary study of human periosteum allografts from this laboratory, the present work has extensively investigated the use of human cadaveric tissue-engineered periosteum-allograft constructs as an approach to healing such serious orthopedic surgical situations. In this current report, human cadaveric periosteum-wrapped bone allografts and counterpart controls without periosteum were implanted subcutaneously in athymic mice (<i>nu/nu</i>) for 10, 20, and, for the first time, 40 weeks. Specimens were then harvested and assessed by histological and gene expression analyses. Compared to controls, the presence of new bone formation and resorption in periosteum-allograft constructs was indicated in both histology and gene expression results over 40 weeks of implantation. Of several genes also examined for the first time, <i>RANKL</i> and <i>SOST</i> expression levels increased in a statistically significant manner, data suggesting that bone formation and the presence of increasing numbers of osteocytes in bone matrices had increased with time. The tissue-engineering strategy described in this study provides a possible means of improving delayed-union or non-union at the healing sites of segmental bone defects or bone fractures. The potential of periosteum and its resident cells could thereby be utilized effectively in tissue-engineering methods and tissue regenerative medicine.


2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Marcello Pilia ◽  
Teja Guda ◽  
Mark Appleford

The need for a suitable tissue-engineered scaffold that can be used to heal load-bearing segmental bone defects (SBDs) is both immediate and increasing. During the past 30 years, various ceramic and polymer scaffolds have been investigated for this application. More recently, while composite scaffolds built using a combination of ceramics and polymeric materials are being investigated in a greater number, very few products have progressed from laboratory benchtop studies to preclinical testing in animals. This review is based on an exhaustive literature search of various composite scaffolds designed to serve as bone regenerative therapies. We analyzed the benefits and drawbacks of different composite scaffold manufacturing techniques, the properties of commonly used ceramics and polymers, and the properties of currently investigated synthetic composite grafts. To follow, a comprehensive review ofin vivomodels used to test composite scaffolds in SBDs is detailed to serve as a guide to design appropriate translational studies and to identify the challenges that need to be overcome in scaffold design for successful translation. This includes selecting the animal type, determining the anatomical location within the animals, choosing the correct study duration, and finally, an overview of scaffold performance assessment.


2010 ◽  
Vol 16 (5) ◽  
pp. 1051-1058 ◽  
Author(s):  
Henriette C. Kroese-Deutman ◽  
Joop G.C. Wolke ◽  
Paul H.M. Spauwen ◽  
John A. Jansen

Sign in / Sign up

Export Citation Format

Share Document