Evaluation of surgical fixation methods for the implantation of melt electrowriting-reinforced hyaluronic acid hydrogel composites in porcine cartilage defects

Jonathan H Galarraga; Hannah M Zlotnick; Ryan C Locke; Sachin Gupta; Natalie L Fogarty; Kendall M Masada; Brendan D Stoeckl; Lorielle Laforest; Miguel Castilho; Jos Malda; Riccardo Levato; James L Carey; Robert L Mauck; Jason A Burdick

doi:10.18063/ijb.775

Evaluation of surgical fixation methods for the implantation of melt electrowriting-reinforced hyaluronic acid hydrogel composites in porcine cartilage defects

Int J Bioprint. 2023 Jun 14;9(5):775. doi: 10.18063/ijb.775. eCollection 2023.

Authors

Jonathan H Galarraga¹, Hannah M Zlotnick^{1

2

3}, Ryan C Locke^{2

3}, Sachin Gupta^{2

3}, Natalie L Fogarty³, Kendall M Masada³, Brendan D Stoeckl^{1

2

3}, Lorielle Laforest³, Miguel Castilho^{4

5}, Jos Malda^{4

6}, Riccardo Levato^{4

6}, James L Carey^{2

3}, Robert L Mauck^{1

2

3}, Jason A Burdick^{1

7}

Affiliations

¹ Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA.
² Translational Musculoskeletal Research Center, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
³ Department of Orthopaedic Surgery, McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, PA, USA.
⁴ Department of Orthopaedics, University Medical Center-Utrecht, Utrecht, The Netherlands.
⁵ Department of Biomedical Engineering, Technical University of Eindhoven, Eindhoven, The Netherlands.
⁶ Department of Clinical Sciences, Utrecht University, Utrecht, The Netherlands.
⁷ BioFrontiers Institute and Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO, USA.

Abstract

The surgical repair of articular cartilage remains an ongoing challenge in orthopedics. Tissue engineering is a promising approach to treat cartilage defects; however, scaffolds must (i) possess the requisite material properties to support neocartilage formation, (ii) exhibit sufficient mechanical integrity for handling during implantation, and (iii) be reliably fixed within cartilage defects during surgery. In this study, we demonstrate the reinforcement of soft norbornene-modified hyaluronic acid (NorHA) hydrogels via the melt electrowriting (MEW) of polycaprolactone to fabricate composite scaffolds that support encapsulated porcine mesenchymal stromal cell (pMSC, three donors) chondrogenesis and cartilage formation and exhibit mechanical properties suitable for handling during implantation. Thereafter, acellular MEW-NorHA composites or MEW-NorHA composites with encapsulated pMSCs and precultured for 28 days were implanted in full-thickness cartilage defects in porcine knees using either bioresorbable pins or fibrin glue to assess surgical fixation methods. Fixation of composites with either biodegradable pins or fibrin glue ensured implant retention in most cases (80%); however, defects treated with pinned composites exhibited more subchondral bone remodeling and inferior cartilage repair, as evidenced by micro-computed tomography (micro-CT) and safranin O/fast green staining, respectively, when compared to defects treated with glued composites. Interestingly, no differences in repair tissue were observed between acellular and cellularized implants. Additional work is required to assess the full potential of these scaffolds for cartilage repair. However, these results suggest that future approaches for cartilage repair with MEW-reinforced hydrogels should be carefully evaluated with regard to their fixation approach for construct retention and surrounding cartilage tissue damage.

Keywords: Cartilage Repair; Fibrin Glue; Hydrogel; Melt electrowriting; Mesenchymal Stromal Cells.

Abstract

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