First injectable nano-apatite scaffold shows promise for bone regeneration
A study to develop mouldable, mechanically strong and in situ hardening calcium phosphate cement (CPC) composite scaffolds for bone regeneration showed positive results with potential applications in various dental, craniofacial, and orthopaedic reconstructions. The CPC scaffolds were strong, tough, macroporous and osteoconductive and showed potential for injection in minimally invasive surgeries, and in delivering osteogenic cells and osteoinductive growth factors to promote bone regeneration. Professor Hockin Xu from the Department of Endodontics, Prosthodontics and Operative Dentistry, at the University of Maryland Dental School in Baltimore, explained why the study is significant.
Question: Briefly explain the choice of material for the injectable scaffolds in your study.
Hockin Xu: The foundation material for the scaffolds is a calcium phosphate cement (CPC) powder that is mixed with an aqueous liquid to form a paste that can be injected, or molded to the desired shape and contour, and set in situ to provide intimate adaption to complex bone cavity shapes. CPC powder was approved for clinical use by the Food and Drug Administration in 1996. We can add chitosan lactate (a biocompatible and biodegradable polymer) and a degradable fibers made from a poly(lactide-co-glycolide) copolymer to provide excellent reinforcement and strength at the early stages of implantation.
Cells can be introduced into the scaffold by first encapsulating them in a sodium alginate (a biocompatible biopolymer) to protect them from the initial cement setting reaction. Finally, diffusible growth factors can be homogenously mixed into the CPC paste and subsequently released over time to enhance bone healing and regeneration. By tailoring the microstructure of the CPC scaffold, we can alter the release profile of the growth factors that have been incorporated.
Question: What are the most significant outcomes of your study?
Hockin Xu: We have developed the first injectable, load-bearing and bone-mimicking nano-apatite scaffold. We were able to improve the load-bearing capability of the scaffold for bone repair, create macropores or channels for cell infiltration and tissue ingrowth, tailor the rates to match new bone formation rates, and quantify the relationships between matrix, fiber, porosity and composite properties. For minimally invasive surgeries, the injectability was substantially improved as were the mechanical properties.
These new composites were non-cytotoxic and supported the adhesion, spreading, proliferation and viability of osteoblast-like cells. Osteoblast cells were able to infiltrate into the macropores, establish cell–cell junctions, and anchor to the nano-apatite walls of the pores. Furthermore, cell–CPC–chitosan–mesh constructs were formulated for cell delivery to enhance bone healing. Protein release from CPC could be regulated to be application-specific by altering the powder to liquid ratio and chitosan content, thereby altering the scaffold porosity.
Question: Your conclusion states that this method has potential applications in dental, craniofacial and orthopaedic surgery. How do you see this being of particular benefit to the dental and craniofacial regions?
Hockin Xu: CPC –based scaffolds may be ideally suited for surgical procedures in the dental and craniofacial regions because of their ability to be molded to a desired shape and set to form a scaffold for bone ingrowth. Esthetics and shape are critically important for craniofacial repairs. Potential applications include major reconstructions of the maxilla or mandible after trauma or tumor resection, and support of metal dental implants or augmentation of deficient implant sites. Each of these applications could benefit from a moldable implant with improved fracture resistance and rapid osteoconduction. Other potential uses include minimally invasive surgeries, such as in situ fracture fixation, and percutaneous vertebroplasty to fill and strengthen osteoporotic bone lesions at risk for fracture.
Question: Based on the results, what is needed next to develop this concept further and see that it becomes a regularly used treatment?
Hockin Xu: While we have demonstrated the fundamental physicochemical and biological properties of these materials in a laboratory setting, the behaviour of these novel materials in an in vivo environment have yet to be explored. Therefore, the next step in the development of these materials is to perform animal studies in order to evaluate their properties over time as well as the host response to the implants. Furthermore, the flexibility offered in the fabrication of moldable/injectable macroporous scaffolds with reinforcement and the delivery of growth factors and cells may have wide applicability to other tissue engineering systems.
'Injectable and strong nano-apatite scaffolds for cell/growth factor delivery and bone regeneration’
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A study to develop mouldable, mechanically strong and in situ hardening calcium phosphate cement (CPC) composite scaffolds for bone regeneration showed positive results with potential applications in various dental, craniofacial, and orthopaedic reconstructions. The CPC scaffolds were strong, tough, macroporous and osteoconductive and showed potential for injection in minimally invasive surgeries, and in delivering osteogenic cells and osteoinductive growth factors to promote bone regeneration. Professor Hockin Xu from the Department of Endodontics, Prosthodontics and Operative Dentistry, at the University of Maryland Dental School in Baltimore, explained why the study is significant.
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