Axial Biologics Advanced Bone Grafts
Based on NanoCor Technology
Overview
Advanced bone graft products are specifically designed to take an active role in bone formation. Axial Biologics has
developed a portfolio of advanced synthetic bone graft products based on the company’s proprietary NanoCor technology. NanoCor is an innovative graft material that was engineered to improve the bone regeneration process by combining multiple advanced bone formation characteristics into a single material.
NanoCor utilizes four advanced material properties to achieve this: (1) a nanocrystalline surface, (2) a bone-like mineral composition, (3) a biomimetic porosity, and (4) an optimized dual-stage resorption profile to enhance the bone healing response. These characteristics are each based on well-established principles of improving bone formation through a material’s nanostructure, composition, pore architecture, and resorption.
Nanostructured Surface
Unlike standard calcium phosphate (CaP) bone graft products that have a relatively smooth surface, the surface of NanoCor-based bone graft products has a nanocrystalline structure. This surface difference is evident in the scanning electron microscope (SEM) images below, where the NanoCor surface is completely covered with a random assembly of nanoplates, while the competitive product has an aggregated surface consisting of smooth geometric crystals
(Figure 1).
Figure 1. Magnified SEM image of the NanoCor granule surface (left) and a competitive CaP product (right)
At the cellular level, nanostructured surfaces have been shown to improve cellular interactions during bone formation. When bone forming osteoblasts and stem cells come in contact with a nano-surface, the crystals put strain on the cell membrane causing the cell to sense it is under a mechanical load. This causes osteoblasts to increase cell function and causes stem cells to convert into osteoblasts (differentiation). These effects have been confirmed by several independent laboratory studies. In particular, Zhang et al. (2017) demonstrated that nanostructured surfaces caused an increase in osteoblast proliferation and function, and were also able to convert stem cells into osteoblasts [1]. Duan et al. (2018) conducted an in vivo bone defect study comparing a nanocrystalline calcium phosphate material against a smooth-surface calcium phosphate material [2]. In this study, implant sites were evaluated at 4, 12, and 26 weeks, and the amount of new bone was quantified. At 4 weeks, the data showed that the nanostructured surface resulted in a faster bone healing response with significantly more bone than the other groups. By 12 and 26 weeks, the nanostructured grafts resulted in more mature bone and bone marrow. These studies demonstrated that a nanostructured surface (regardless of the material composition) can promote cell growth and result in faster bone healing.
Unique Dual-Phase Composition – HCA and Optimal Resorption
In addition to the nanocrystalline structure, NanoCor has a distinctly unique dual-phase composition that imparts advantageous properties to the material. The base material used to create NanoCor technology is calcium carbonate that has a biomimetic porous structure that resemble human cancellous bone.
Using a proprietary manufacturing process, a thin outer region of the porous calcium carbonate structure is converted into nanocrystalline hydroxycarbanoapatite (HCA). HCA is a carbonated form of hydroxyapatite that closely resembles the mineral component of bone. It is also the same bioactive material that forms on the surface of Bioglass, giving it an advanced osteoconductive surface. NanoCor’s unique two- component composition is shown in the SEM image in Figure 2 . Due to this dual-region composition, NanoCor possess a combination of properties not found in other bone graft products.
Figure 2. SEM image of NanoCor’s distinct dual-region composition (1,000X)
Advantage of HCA
The main advantage of having the entire NanoCor surface covered with HCA is that it allows for faster bone formation. This is directly based on its similarity to bone mineral. Although other ceramic-based bone graft materials contain the core elements found in bone [calcium (Ca) and phosphorus (P)] and allow bone growth on their surface (osteoconduction), they do not contain carbonate. As a result, surface bone formation occurs in stages on CaP materials, with osteoclasts initially preparing the surface, followed by osteoblasts building the new bone. With HCA, the initial osteoclast process is significantly accelerated due to the presence of carbonate and the resulting similarity of HCA to natural bone mineral. Bone formation on HCA essentially “skips” the preparation phase seen with standard CaP ceramics. This results in faster activation of the osteoblasts [3], and a faster bone formation process [4]. In particular, an in vivo study conducted by Hayashi et al. evaluated the bone formation response of HCA and two common CaP materials (tricalcium phosphate – TCP and hydroxyapatite – HA). All materials were fabricated with the exact same bone graft scaffold structure and implanted into a long bone defect. The results showed that significantly more bone had formed faster in the HCA group compared to the TCP and HA groups at both the 4-week and 12-week time points. This was more pronounced at the earlier time-point (4-weeks) which showed that HCA resulted 4.3X more bone than TCP and 14.3X more than HA [4].
Optimal Dual-Stage Resorption
With standard ceramic bone graft materials, the resorption rate is dictated by the material. For example, HA is typically slowly resorbing (~1%/year), while TCP resorbs at faster rate with a broad range of 6-24 months. These resorption times are inherent to the materials and can only be partially changed by mixing HA and TCP together (called biphasic calcium phosphate – BCP). NanoCor is unique in that its dual-region composition (HCA-surface with calcium carbonate core) allows resorption to be directly controlled by the thickness of the HCA surface. This is due to the slower resorption of the HCA surface compared to the calcium carbonate core. Due to this property, the resorption profile for NanoCor was optimized to match the formation of new bone. This is important since all bone graft materials primarily function as a scaffold for new bone growth. If the scaffold resorbs too quickly before bone formation is complete, then a void can develop. If it resorbs too slowly, then the implant occupies space that should be filled in with new bone.
Figure 3. False colored histology image showing NanoCor resorption and new bone formation
With decades of experience, Axial Biologics scientists have fine-tuned the HCA layer thickness to create an advanced bone graft material with an optimal resorption profile. This was seen in an in vivo study evaluating the bone formation response and resorption of the NanoCor granules in the posterolateral spine [7]. After 3 months of implantation, partial resorption of the HCA layer allowed bone growing on the surface to penetrate into the calcium carbonate region ( Figure 3). As the calcium carbonate was resorbed, new bone formed directly in its place. This demonstrated an optimal resorption/bone formation response.
Biomimetic Pore Architecture
Bone graft porosity is one of the key material properties that can impact healing and graft function. While all osteoconductive materials allow for bone formation on the surface of the implant, the pore size and interconnectivity dictate how much bone will form within the graft. Additionally, the porosity affects the strength of the scaffold and determines whether it will resist crushing during intraoperative handling.
The NanoCor graft material has a unique biomimetic structure that provides an optimal scaffold for bone formation. With an average pore size of 500 microns (µm) and a 100% interconnected porosity, the NanoCor structure closely resembles the natural blueprint of cancellous bone (Figure 4).
Figure 4. SEM comparison of the pore architecture of NanoCor (left) and cancellous bone (right)
Figure 5. 100% interconnected porosity allows immediate bone growth into the center of a NanoCor implant.
The benefit of the NanoCor pore structure is that the 100% interconnected porosity provides a directly accessible pathway to the interior of the graft site. In combination with a uniform 500 µm pore size, bone is able to grow from the periphery of the graft through the entire NanoCor structure ( Figure 5). Additionally, the 500 µm average pore size falls within the optimal range (300-500 µm) for bone in-growth. This is based on studies showing that pores that are too small (typically <100 µm) can limit bone in-growth and pores that are too large can slow down the bone formation process [5,6].
In addition to functioning as a scaffold for new bone formation, NanoCor’s biomimetic structure also provides an optimal combination of strength and porosity. This is especially important for Axial Biologics’s Agilon® Moldable and Strip products and graft applications where the materials are compressed or impacted. The NanoCor structure is compression resistant which eliminates crushing during standard intraoperative handling and placement. This is an important feature since the main function of a bone graft is to serve as an osteoconductive scaffold. Porous products with weak structures can be easily crushed or pulverized which can significantly reduce their ability to support bone growth.
Conclusion
NanoCor represents an advanced synthetic bone graft material that was engineered with specific structural and compositional properties to enhance the bone healing process and provide a significant improvement over standard bone graft materials. The combination of a nanostructured surface, an HCA composition, a biomimetic pore architecture, and an optimized resorption profile results in a unique material that is actively involved in the healing process. Axial Biologics’s NanoCor-based advanced bone graft products provide surgeons with state-of-the-art grafting solutions that can improve clinical outcomes.
References:
- Zhang et al. J. of Tissue Eng. And Regen. Med. 11: pp 3273-3283 (2017)
- Duan et al. ACS Biomater. Sci. Eng. 4: pp 3347-3355 (2018)
- Spence et al. Key Eng. Materials Vols. 309-31: pp 207-210 (2006)
- Hayashi et al. Materials Today Bio. 4: pp. 1-11 (2019)
- Hulbert et al. Biomed. Mater. Res. Symp. 2-1: pp. 161-229 (1971)
- Kaplan et Biomaterials. 26: pp. 5474-5491 (2005)
- Data on file
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