Prosthetic materials are largely used in surgery and tissue engineering. However, many postoperative complications are due to poor integration of the materials, which delays the healing process. The objective of our study was to develop a synthetic scaffold that, according to histopathological and biomechanical criteria, would achieve both tolerance and efficiency. In this study, we evaluated the effect of intramuscular and subcutaneous implantation of a new hybrid mesh (HM) in rats. This HM was composed of clinical grade polypropylene mesh embedded in a polysaccharide hydrogel. Histological and biomechanical studies on the polysaccharide gel alone and on HM were performed 15 and 30 days after implantation, and then compared with two clinically used materials, porcine decellularized small intestinal submucosa and a polypropylene mesh. Results showed that the incorporation of a polypropylene mesh within the polysaccharide hydrogel led to the absence of adverse effects and better tissue organization. Thus, this new synthetic biocompatible HM with suitable properties for tissue repair appears to be a promising material for clinical applications.