**Stability Evaluation and Degradation Studies of DAC**® **Hyaluronic-Polylactide Based Hydrogel by DOSY NMR Spectroscopy**

**Tatiana Guzzo <sup>1</sup> , Fabio Barile <sup>1</sup> , Cecilia Marras <sup>1</sup> , Davide Bellini <sup>2</sup> , Walter Mandaliti <sup>3</sup> , Ridvan Nepravishta <sup>3</sup> , Maurizio Paci <sup>3</sup> and Alessandra Topai 1,\***


Received: 6 October 2020; Accepted: 21 October 2020; Published: 24 October 2020

**Abstract:** The stability and the degradation of polymers in physiological conditions are very important issues in biomedical applications. The copolymer of hyaluronic acid and poly-D,L-lactic acid (made available in a product called DAC®) produces a hydrogel which retains the hydrophobic character of the poly-D,L-lactide sidechains and the hydrophilic character of a hyaluronic acid backbone. This hydrogel is a suitable device for the coating of orthopedic implants with structured surfaces. In fact, this gel creates a temporary barrier to bacterial adhesion by inhibiting colonization, thus preventing the formation of the biofilm and the onset of an infection. Reabsorbed in about 72 h after the implant, this hydrogel does not hinder bone growth processes. In the need to assess stability and degradation of both the hyaluronan backbone and of the polylactic chains along time and temperature, we identified NMR spectroscopy as a privileged technique for the characterization of the released species, and we applied diffusion-ordered NMR spectroscopy (DOSY-NMR) for the investigation of molecular weight dispersion. Our diffusion studies of DAC® in physiological conditions provided a full understanding of the product degradation by overcoming the limitations observed in applying classical chromatography approaches by gel permeation UV.

**Keywords:** DAC® HA-PLA copolymers; biopolymer degradation; polymer stability; DOSY NMR
