Elsevier

Materials Letters

Volume 265, 15 April 2020, 127457
Materials Letters

Biomicroconcretes based on the hybrid HAp/CTS granules, α-TCP and pectins as a novel injectable bone substitutes

https://doi.org/10.1016/j.matlet.2020.127457Get rights and content

Highlights

  • Novel biomicroconcretes based on hybrid HAp/CTS granules, α-TCP and pectins were developed.

  • Biomicroconcretes possessed excellent injectability, high cohesion and washout resistance.

  • Developed materials can be considered as a dual-setting system.

  • Type of pectins significantly affect mechanical properties of final materials.

  • Obtained biomicroconcretes can be considered as novel injectable bone substitutes.

Abstract

In this work, novel bone substitutes in the form of biomicroconcretes with high surgical handiness and satisfactory mechanical properties were developed. Materials were composed of hybrid hydroxyapatite/chitosan (HAp/CTS) granules as aggregate, α-TCP as a setting phase, and pectin solutions as a liquid phase. Two types of low esterified amidated pectins from citrus peels (CP) and apple pomace (AP) and also two fractions of HAp/CTS granules of size between 300 and 400 µm and 400–600 µm were used. The presence of pectins significantly improved surgical handiness and allowed to obtain injectable biomicroconcretes. Synergistic effect of fast internal crosslinking of low esterified pectins, induced by Ca2+ released from α-TCP, together with setting reaction of highly reactive α-TCP (dual setting system) resulted in excellent cohesion of the final materials. By the use of different type of pectins (AP, CP) one can control mechanical properties of the materials. The results showed that pectins from citrus peels more effectively improved compressive strength. The biomicroconcretes obtained in this work showed great potential for the use as novel bone substitutes, however, they require further studies, especially biological evaluation.

Introduction

An increasing number of surgeries performed on young people, as well as an ageing society force scientists to develop new bone substitutes with superior properties, enhancing the bone healing process. Commonly used bone substitutes include self-setting calcium phosphate cements (CPCs), the main component of which is, for instance, α-tricalcium phosphate (α-TCP). The setting reaction of CPCs is based on the hydrolysis of α-TCP to CDHA in the presence of water or phosphate solutions, frequently used as a liquid phase in commercially used cements [1]. The main advantage is that CPCs can be used as injectable systems, which allow one to use them in minimally invasive procedures. However, currently available commercially used cements suffer from poor injectability with liquid demixing and insufficient washout resistance in contact with biological fluids or blood [2]. One of the strategies to overcome the aforementioned limitations is to use polymeric additives to CPCs, such as natural hydrogels based on collagen, gelatine, carboxymethylcellulose, hyaluronic acid or chitosan [3].

Calcium phosphate granules (CPGs) are another potential graft substitutes used for bone regeneration in orthopaedics and dentistry. Granule-shaped calcium phosphates allow for accurate filling of bone defect while mixing with patient’s blood improves their surgical handiness. CPGs porosity favours bone-forming cell colonization and allows for the incorporation of drugs or growth factors. However, in most cases implantation of granules requires traditional open surgery [4], [5].

In this work, the combination of above-mentioned bone substitutes to obtain a new type of materials – biomicroconcretes was proposed. Materials composed of hybrid hydroxyapatite/chitosan (HAp/CTS) granules as aggregate, α-TCP as a setting phase, and pectin solutions as a liquid phase, were developed. Hybrid granules combine advantages of hydroxyapatite (i.a. biocompatibility, bioactivity, osteogenic potential, and osteoconductivity) and CTS (i.a. rapid biodegradation, high biocompatibility, haemostatic and antibacterial properties). As it was shown in previous work [6], electrostatic complexes between positively charged, protonated amine groups of chitosan and the negative phosphate species were created, conforming hybrid character of the granules. HAp/CTS granules showed improved mechanical properties, therefore they can be considered as a reinforcing phase in biomicroconcretes. In turn, a highly reactive α-TCP phase provides in situ setting reactions in physiological conditions. Pectins represent a group of environmentally friendly, abundantly available, and therefore inexpensive raw materials. They are biocompatible, biodegradable and show crosslinking ability upon divalent ions, therefore pectins are expected to increase washout resistance [7]. Furthermore, thanks to water-binding capacity, they can improve the injectability of the materials.

The aim of this study was to develop new bone substitutes with high surgical handiness and satisfactory mechanical properties. Two types of low esterified amidated pectins from citrus peels and apple pomace and also two fractions of HAp/CTS granules were used. According to the literature review, these are the first studies on that type of bone graft substitutes in the form of biomicroconcretes.

Section snippets

Materials and methods

The hybrid hydroxyapatite-chitosan (HAp/CTS) granules and highly reactive α-tricalcium phosphate (α-TCP) powder were synthesized using wet chemical methods. The procedure of obtaining the HAp/CTS granules, containing 17 wt% of chitosan, was described by Zima [6]. Two fractions of granules of size between 300 and 400 µm and 400–600 µm were used. The α-TCP powder was synthesized according to the procedure described previously [8]. As a liquid phase, two types of low esterified amidated pectins

Results and discussion

The results showed that calcium phosphate-based biomicroconcretes, developed in this study, possessed excellent injectability, and no phase separation was observed during extrusion from the syringe. Furthermore, it can be seen that the biomicroconcretes held its initial shape after extrusion to SBF, even after 28-day incubation, indicating high cohesion and washout resistance (Fig. 1.). Three mechanisms underlying these phenomena, related to the presence of pectins, can be provided. The first

Conclusions

The presence of pectins significantly improved surgical handiness and allowed to obtain injectable biomicroconcretes. Synergistic effect of fast internal crosslinking of low esterified pectins, induced by Ca2+ released from α-TCP, together with setting reaction of highly reactive α-TCP (dual setting system) resulted in excellent cohesion of final materials. By the use of a different type of pectins (AP, CP) and various HAp/CTS granule sizes one can control mechanical properties of the

Authors contribution

M.D. and A.Z. conceived and planned the experiments. M.D., E.C. and J.C carried out the experiments. M.D and E.C. contributed to sample preparation. M.D., A.Z., E.C. J.C. and A.S. contributed to the interpretation of the results. M.D. took the lead in writing the manuscript with the consultation of the rest of the authors. All authors discussed the results and commented on the manuscript. A.S. supervised the project.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

This work was supported by the National Science Centre, Poland Grant No. 2017/27/B/ST8/01173. Authors thank Herbstreith & Fox Company for delivering pectins.

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