(17b) Evaluation of Catechol Use As a Crosslinker and to Functionalize Chitosan to Produce a Bone Adhesive with Aqueous Adhesion

Sarmiento, P. A., Universidad de los Andes
Vargas, J. G., Universidad de los Andes
Salcedo, F., Universidad de los Andes
A comminuted fracture is a fracture, in which a bone breaks in 3 or more pieces. These fractures represent a challenge for current medicine, since their treatment through conventional processes; as the use of plates, screws, and wires; requires complex surgery and in some cases the shortening of the bone[1–3]. Additionally, because of the difficulty in fixating some fragments, these practices often end up in a wrong fixation [4]. As a solution, the use of synthetic osseous cements has been encouraged as an alternative. Nevertheless, this adhesives that usually present a great adhesion power, often encounter toxicity problems [5, 6]. Therefore, biological-based adhesives have become a focus of research. Unfortunately, these are unsuccessful at reaching the strength needed in order to allow bone regeneration and proper fixation [5, 7].

Our previous works have shown that for comminuted fracture treatment, the use of a biocomposite based on chitosan, hydroxyapatite, and glutaraldehyde can be used as an adhesive holding a TBS of 0.2MPa[8]. Nevertheless, while testing this hydrogel under aqueous conditions it was evident that the adhesion property was lost. As a solution we propose the implementation of catechol in order to functionalize and crosslink the gels to allow different chemical interactions with the bone mineral and organic matter.

The adhesion mechanism proposed in previous studies depended heavily on the interaction of aldehydes present in the crosslinker to the amino groups on tissue[9]. Nevertheless, when in contact with water, aldehyde groups hydrolyze and as a result there is no interaction to (with) the tissue. Additionally, since glutaraldehyde forms immine links to chitosan, the crosslinking reaction can be reversed under aqueous conditions. Therefore cathecol was proposed as a solution. This structure is a benzenediol functional group and it is used on different applications since it is the responsible for the adhesion of mussels to organic and inorganic surfaces at sea on strong turbulence conditions[10, 11].

In this study, chitosan is functionalized with catechol for different reaction times of 15, 45, 90, 180 and 360 min. This functionalized compounds are characterized by themselves and used to form adhesives. It is determined that it is not possible to produced hydrogels with this polymer. As a result, mixtures between chitosan and catechol-chitosan were proposed as a solution. An analysis of rheological and adhesive properties is conducted in order to determine the combination with more promising results to the proposed application. A reaction time of 15 minutes and a catechol-chitosan proportion of 10% resulted in the most promising gels. This formulation showed adhesion when completely submerged and TBS values close to the obtained in the previous works.

Additionally, the use of polydopamine (a compound with a catechol group) as a crosslinker was evaluated for this formulation and the change in adhesion was analyzed. These adhesives did not show a significant difference in adhesion compared to the glutaraldehyde-crosslinked counterpart. Nevertheless, they were easier to apply when completely submerged given their higher density and lack the toxic disadvantage that glutaraldehyde entails.


  1. Holz U (2015) The elements of fracture fixation. Indian J Orthop 49:682 . doi: 10.4103/0019-5413.168763
  2. Schatzker J, Tile M (1987) The rationale of operative fracture care. Springer-Verlag
  3. 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
  4. Shah JP, Patel SG, Singh B, Shah JP (2012) Jatin Shah’s head and neck surgery and oncology. Elsevier/Mosby
  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. 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
  8. 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
  9. Nair LS (2016) Injectable Hydrogels for Regenerative Engineering. IMPERIAL COLLEGE PRESS
  10. Ryu JH, Hong S, Lee H (2015) Bio-inspired adhesive catechol-conjugated chitosan for biomedical applications: A mini review. Acta Biomater 27:101–115 . doi: 10.1016/j.actbio.2015.08.043
  11. Xu J, Soliman GM, Barralet J, Cerruti M (2012) Mollusk Glue Inspired Mucoadhesives for Biomedical Applications. Langmuir 28:14010–14017 . doi: 10.1021/la3025414