Abstract
With the development of tissue engineering, bone defects, such as fractured long bones or cavitary lesions, may be efficiently repaired and reconstructed using bone substitutes. However, high rates of fusion failure remain unavoidable in spinal fusion surgery owing to the lack of appropriate materials for bone regeneration under such challenging conditions. Parathyroid hormone (PTH), a major regulator of bone remodeling, exerts both anabolic and catabolic effects. In this study, we modified PTH(1–34) and designed and synthesized a novel PTH-related peptide, namely PTHrP-1. Further, we fabricated a local PTHrP delivery device from mesoporous bioactive glass (MBG) to address the need for a suitable material in spinal fusion surgery. Using MBG scaffolds as a control, the biological properties of PTHrP-MBG scaffolds were evaluated in terms of attachment, proliferation, and alkaline phosphatase activity, as well as osteogenic gene and angiogenic gene expression in co-cultured rat bone marrow mesenchymal stem cells (rBMSCs) in vitro. Furthermore, PTHrP-1-MBG scaffolds were tested in a rat posterolateral spinal fusion model. Our data showed that PTHrP-1-MBG scaffolds possessed good ability to facilitate attachment and stimulation of rBMSC proliferation and differentiation. Importantly, the in vivo results revealed that the PTHrP-1-MBG scaffolds facilitated faster new bone formation and a higher rate and quality of spinal fusion. Therefore, the results suggest that devices consisting of the present novel PTHrP and MBG possess wider potential applications in bone regeneration and should serve as a promising bone substitute for spinal fusion.
Highlights
With an increasingly aging population, the prevalence of clinical conditions affecting the spinal column that require surgical treatment is rising
Many previous studies have demonstrated the osteoinductive nature of mesoporous bioactive glass (MBG) itself; our results showed that MBG alone failed to improve rat bone marrow mesenchymal stem cells (rBMSCs) osteo-differentiation.[40]
The results showed completed bridging in 0.1 mg PTHrP-1-MBG scaffolds and 0.5 mg PTHrP-1MBG scaffold groups, while defect bridging was observed in the MBG scaffold group a er 12 weeks of implantation (Fig. 6)
Summary
With an increasingly aging population, the prevalence of clinical conditions affecting the spinal column that require surgical treatment is rising. For the purpose of facilitating patient comfort and mobility, spinal fusion surgery has signi cantly increased over the last few decades.[1,2] To achieve and maintain fusion and intersegmental stability, bone gra s and bone substitutes are frequently adopted.[1] Autologous bone was recognized as the gold standard for obtaining satisfactory spinal fusion.[2] in addition to the limited supply of autologous bone gra , donor site morbidity, and poor bone quality in osteoporotic patients limit the effectiveness of this option.[3,4] allogra bone is widely available, the problems of resorption, exposure, and disease transmission have restricted its use.[5] In order to resolve this challenge, researchers in the orthopedic community have attempted to identify effective alternative methods. The elevated risk of wound-related complications and other complications, such as so tissue swellings, uncontrolled heterotopic ossi cation, and radiculitis, limit the wider therapeutic administration of these osteoinductive molecules.[6,7,8] Existing biomaterials fail to provide an efficacious and safe solution for bone regeneration without concomitant complications, and tissue engineering represents a novel therapy for reliable and efficient bone regeneration
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