Preclinical evaluation of collagen type I scaffolds, including gelatin-collagen microparticles and loaded with a hydroglycolic Calendula officinalis extract in a lagomorph model of full-thickness skin wound


Previously, we have developed collagen type I scaffolds including microparticles of gelatin-collagen type I (SGC) that are able to control the release of a hydroglycolic extract of the Calendula officinalis flower. The main goal of the present work was to carry out the preclinical evaluation of SGC alone or loaded with the C. officinalis extract (SGC-E) in a lagomorph model of full-thickness skin wound. A total of 39 rabbits were distributed in three groups, of 13 animals each. The first group was used to compare wound healing by secondary intention (control) with wound healing observed when wounds were grafted with SGC alone. Comparison of control wounds with wounds grafted with SGC-E was performed in the second group, and comparison of wounds grafted with SGC with wounds grafted with SGC-E was performed in the third group. Clinical follow-ups were carried in all animals after surgery, and histological and histomorphometric analyses were performed on tissues taken from the healed area and healthy surrounding tissue. Histological and histomorphometric results indicate that grafting of SGC alone favors wound healing and brings a better clinical outcome than grafting SGC-E. In vitro collagenase digestion data suggested that the association of the C. officinalis extract to SGC increased the SGC-E cross-linking, making it difficult to degrade and affecting its biocompatibility.

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The Colombian Department of Science, Technology, and Innovation (COLCIENCIAS) (grant 1101-521-28661) and the Universidad Nacional de Colombia (MSc Program in Microbiology) supported this work. We would like to thank Dr. Luis Fernando Ospina, Oswaldo Escobar, and the members of the Tissue Engineering Group for helping us with the animal experiments; Dr. Lucía Botero for her histological advice; and PhD candidate Julia A. Morales for editing the manuscript. Diana Millán and Ronald A. Jiménez were supported by COLCIENCIAS (grant 1101-521-28661).

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Corresponding author

Correspondence to M. R. Fontanilla.

Ethics declarations

All institutional and national guidelines for the care and use of laboratory animal were followed.

Conflict of interest

Diana Millán, Ronald A. Jiménez, Luis E. Nieto, Itali Linero, Manuel Laverde, and Marta R. Fontanilla declare that they have no conflict of interest. The authors declare no competing financial interests.

Additional information

D. Millán and R. A. Jiménez contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supp. 1

Data sheet of Calendula officinalis flower extract. Full details on batch number, content, preparation method, and quality control of the hydroglycolic C. officinalis flower extract are presented.

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Millán, D., Jiménez, R.A., Nieto, L.E. et al. Preclinical evaluation of collagen type I scaffolds, including gelatin-collagen microparticles and loaded with a hydroglycolic Calendula officinalis extract in a lagomorph model of full-thickness skin wound. Drug Deliv. and Transl. Res. 6, 57–66 (2016).

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  • Collagen type I
  • Scaffolds
  • Gelatin-collagen microparticles
  • Calendula officinalis L. flowers extract
  • Full-thickness wounds