Abstract
Generation of biocompatible and biomimetic tissue-like biomaterials is crucial to ensure the success of engineered substitutes in tissue repair. Natural biomaterials able to mimic the structure and composition of native extracellular matrices typically show better results than synthetic biomaterials. The aim of this study was to perform an in vivo time-course biocompatibility analysis of fibrin-agarose tissue-like hydrogels at the histological, imagenological, hematological, and biochemical levels. Tissue-like hydrogels were produced by a controlled biofabrication process allowing the generation of biomechanically and structurally stable hydrogels. The hydrogels were implanted subcutaneously in 25 male Wistar rats and evaluated after 1, 5, 9, and 12 weeks of in vivo follow-up. At each period of time, animals were analyzed using magnetic resonance imaging (MRI), hematological analyses, and histology of the local area in which the biomaterials were implanted, along with major vital organs (liver, kidney, spleen, and regional lymph nodes). MRI results showed no local or distal alterations during the whole study period. Hematology and biochemistry showed some fluctuation in blood cells values and in some biochemical markers over the time. However, these parameters were progressively normalized in the framework of the homeostasis process. Histological, histochemical, and ultrastructural analyses showed that implantation of fibrin-agarose scaffolds was followed by a progressive process of cell invasion, synthesis of components of the extracellular matrix (mainly, collagen) and neovascularization. Implanted biomaterials were successfully biodegraded and biointegrated at 12 weeks without any associated histopathological alteration in the implanted zone or distal vital organs. In summary, our in vivo study suggests that fibrin-agarose tissue-like hydrogels could have potential clinical usefulness in engineering applications in terms of biosafety and biocompatibility.
Highlights
The main objective of tissue engineering (TE) is to generate artificial biological substitutes to repair damaged human tissues and organs
In order to improve the biomechanical properties of fibrin hydrogels for tissue engineering applications, researchers combined this biomaterial with polyurethane (Lee et al, 2005), polycaprolactone-based polyurethane (Eyrich et al, 2007b; Wittmann et al, 2016) and polycaprolactone (Van Lieshout et al, 2006), among other biomaterials, with variable results
To generate a Fibrin-agarose tissue-like hydrogels (FATLH) with a volume of 10 ml, 7.6 ml of human plasma obtained from healthy blood donors were mixed with 750 μl of Dulbecco’s modified Eagle’s medium (DMEM) and 150 μl of tranexamic acid used as anti-fibrinolytic agent (Amchafibrin, Fides-Ecofarma, Valencia, Spain)
Summary
The main objective of tissue engineering (TE) is to generate artificial biological substitutes to repair damaged human tissues and organs. Among the numerous scaffolds used in TE, hydrogels have great potential due to their excellent biocompatibility due to their high hydration rate, diffusive and exchange properties allowing cell functions and viability (Ahmed et al, 2008; Carriel et al, 2014; Scionti et al, 2014). In this regard, one of the most widely used hydrogels in TE is fibrin, which offers some relevant advantages: low price, good cellbiomaterial interactions, fibrillary, and porous pattern and easy handling (Rosso et al, 2005; Swartz et al, 2005). In order to improve the biomechanical properties of fibrin hydrogels for tissue engineering applications, researchers combined this biomaterial with polyurethane (Lee et al, 2005), polycaprolactone-based polyurethane (Eyrich et al, 2007b; Wittmann et al, 2016) and polycaprolactone (Van Lieshout et al, 2006), among other biomaterials, with variable results
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