(741c) Evaluation of the Procedure to Obtain Chitosan Based Gels with Potential Use As Bone Adhesive on Clinical Settings

Comminuted fractures are defined as fractures in which an anatomical region is broken into multiple pieces. Medical treatments today have problems dealing with this kind of fractures because of the complications associated with these injuries. Among the techniques used nowadays to treat such wounds are the closed reduction, external fixation of pins, internal fixation with wires and internal reduction and fixation with the use of plates, screws, and wires[1]. Some of these treatments end up in a wrong fixation of fragments in the fracture [2]. Furthermore, in most cases, there are fragments so small that they cannot be fixated by any of the aforementioned techniques and are therefore discarded[3]. This only worsens the treatment, since the fact of having missing pieces may require a shortening in the bone to make an appropriate fixation with traditional methods and avoid an improper fixation[4].

Acknowledging this issue, the use of synthetic osseous adhesives can be considered as an alternative. Such adhesives usually present a great adhesion power, but they fail on being biocompatible [5–8]. Due to the lack of biodegradation and biocompatibility properties, the use of synthetic adhesives is restricted to big fragments of bone. On the other side, some biological based adhesives have been under research, but none of them have been able to reach the desired strength to hold through the stress a bone is constantly under [5, 9–11]. Therefore, this work proposes the use of chitosan as the main component for a bio adhesive that allows fixation of small bone fragments. Additionally, this adhesive is designed to allow cellular growth and biodegradation in the human body, which allows faster recovery without harming the patient.

Previous works have achieved to formulate this bio-adhesive, using three other components apart of chitosan. Two of the components are biocompatible agents that allow the adhesive to be more similar to the bone extracellular matrix, giving it a better chance of cellular growth and differentiation [12–14]. The third component is used as a cross linker to link the polymer chains and form a gel[15]. Due to the chemical interaction of the components with the polymer, the preparation method design is in stages. This allows the different components to interact with chitosan, and to restrict the crosslinking process giving properties to the hydrogels intended to work as bone adhesives (including wanted gelation time, malleability, wettability and mechanical strength.) [14, 15]. Accordingly, the method developed has two mixing stages. Each of these stages uses a different set of stirrers and impellers. The first stage is mixed with a DISPERMAT® LC30 and a Lightweight stainless steel dispersion impeller of 25mm. The second stage is done with a Mechanical stirrer EUROSTAR power control-visc 6000 (IKA) and a three-blade boat propeller of 35mm[14, 15].

While performing preclinical trials, we identified the need to modify the preparation process of the osseous bio adhesive. This was done since the equipment used to produce the gels on laboratory settings could not be sterilized and transported to a clinical setting. Therefore, in this study, a throughout evaluation of chemical and mechanical properties of adhesives prepared with different agitation methods is conducted. In it, different small and easy to sterilize home appliances’ motors with fixed velocities and impellers were tested. Additionally, the most viable motor was tested with the original impellers (dispersion and three blade boat) to analyze what the critical factors in the production process are. The analysis of these gels has demonstrated that rheological properties do not reflect the difference in mechanical strength as believed before this work. Nevertheless, the change of the equipment used during the preparation of the adhesive changed the mechanical properties of it, decreasing the adhesive strength up to 62%. Additionally, it has been proven that one of the agitation stages has a bigger impact on the adhesive properties of the product. The mixing velocity resulted to have a more significant impact on the properties of the bioadhesive compared to the impeller used. Based on the given results, we propose a novel mixing method to produce gels on clinical settings and decrease the difference in the mechanical properties comparing the adhesive prepared on clinical and laboratory settings.

The results of the chemical and mechanical tests on the gels produced using both the laboratory and the clinical set of equipment will be presented in detail. Furthermore, we present the novel formulation procedure for the osseous chitosan-based bio-adhesive.

References

1. Holz U (2015) The elements of fracture fixation. Indian J Orthop 49:682. doi: 10.4103/0019-5413.168763

2. Shah JP, Patel SG, Singh B, Shah JP (2012) Jatin Shah’s head and neck surgery and oncology. Elsevier/Mosby

3. Schatzker J, Tile M (1987) The rationale of operative fracture care. Springer-Verlag

4. Herscovici D, Scaduto JM (2014) Assessing Leg Length After Fixation of Comminuted Femur Fractures. Clin Orthop Relat Res 472:2745–2750. doi: 10.1007/s11999-013-3292-0

5. Porter JR, Ruckh TT, Popat KC (2009) Bone tissue engineering: A review in bone biomimetics and drug delivery strategies. Biotechnol Prog 25:NA-NA. doi: 10.1002/btpr.246

6. Arora M, Chan EK, Gupta S, Diwan AD (2013) Polymethylmethacrylate bone cements and additives: A review of the literature. World J Orthop 4:67–74. doi: 10.5312/wjo.v4.i2.67

7. Toriumi DM, Raslan WF, Friedman M, Tardy ME (1990) Histotoxicity of Cyanoacrylate Tissue Adhesives: A Comparative Study. Arch Otolaryngol - Head Neck Surg 116:546–550. doi: 10.1001/archotol.1990.01870050046004

8. Fedak PWM, Kolb E, Borsato G, Frohlich DEC, Kasatkin A, Narine K, Akkarapaka N, King KM (2010) Kryptonite Bone Cement Prevents Pathologic Sternal Displacement. Ann Thorac Surg 90:979–985. doi: 10.1016/j.athoracsur.2010.05.009

9. Farrar DF (2012) Bone adhesives for trauma surgery: A review of challenges and developments. Int J Adhes Adhes 33:89–97. doi: 10.1016/j.ijadhadh.2011.11.009

10. Donkerwolcke M, Burny F, Muster D (1998) Tissues and bone adhesives—historical aspects. Biomaterials 19:1461–1466. doi: 10.1016/S0142-9612(98)00059-3

11. Heiss C, Kraus R, Schluckebier D, Stiller A-C, Wenisch S, Schnettler R (2006) Bone Adhesives in Trauma and Orthopedic Surgery. Eur J Trauma 32:141–148. doi: 10.1007/s00068-006-6040-2

12. Swetha M, Sahithi K, Moorthi A, Srinivasan N, Ramasamy K, Selvamurugan N (2010) Biocomposites containing natural polymers and hydroxyapatite for bone tissue engineering. Int J Biol Macromol 47:1–4. doi: 10.1016/j.ijbiomac.2010.03.015

13. Fujihara K, Kotaki M, Ramakrishna S (2005) Guided bone regeneration membrane made of polycaprolactone/calcium carbonate composite nano-fibers. Biomaterials 26:4139–4147. doi: 10.1016/j.biomaterials.2004.09.014

14. Pinzon LM, Cedano FJ, Castro CI, Briceño JC, Casas JP, Tabima DM, Salcedo F (2017) Formulation and Characterization of Chitosan-Based Biocomposites with Potential Use for Bone Adhesion. Int J Polym Mater Polym Biomater 00914037.2016.1263948. doi: 10.1080/00914037.2016.1263948

15. Cedano Serrano FJ, Pinzón LM, Narváez DM, Castro Paéz CI, Moreno-Serrano CL, Tabima DM, Salcedo F, Briceno JC, Casas-Rodriguez JP (2017) Evaluation of a water-resistant and biocompatible adhesive with potential use in bone fractures. J Adhes Sci Technol 31:1480–1495. doi: 10.1080/01694243.2016.1263055