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

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 (Corresponding author), Jason A. Burdick (Corresponding author)

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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.

Original language	English
Pages (from-to)	493-509
Number of pages	17
Journal	International Journal of Bioprinting
Volume	9
Issue number	5
DOIs	https://doi.org/10.18063/ijb.775
Publication status	Published - 2023

Funding

This work received financial support from the AO Foundation through the Osteochondral Defect Collaborative Research Program (AO-OCD Consortium TA1711481: Osteochondral Bone Repair with Innovative Tissue Engineering and 3D Bioactive Composite Scaffold), the National Science Foundation (graduate research fellowship to JHG), the National Institute of Health (R01 AR077362, F31 AR077395, P30 AR069619, T32 AR053461), and the US Department of Veterans’ Affairs (IK6 RX003416, IK1 RX003932). JM and RL acknowledge support from the Dutch Arthritis Society (LLP-12 and LLP-22) and the Gravitation Program “Materials Driven Regeneration” funded by the Netherlands Organization for Scientific Research (024.003.013).

Funders	Funder number
National Science Foundation
National Institutes of Health	P30 AR069619, R01 AR077362, F31 AR077395, T32 AR053461
Department of Veterans Affairs	IK1 RX003932, IK6 RX003416
Dutch Arthritis Society	LLP-22, LLP-12
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	024.003.013

Keywords

Cartilage Repair
Fibrin Glue
Hydrogel
Melt electrowriting
Mesenchymal Stromal Cells

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Galarraga, J. H., Zlotnick, H. M., Locke, R. C., Gupta, S., Fogarty, N. L., Masada, K. M., Stoeckl, B. D., Laforest, L., Castilho, M., Malda, J., Levato, R., Carey, J. L., Mauck, R. L., & Burdick, J. A. (2023). Evaluation of surgical fixation methods for the implantation of melt electrowriting-reinforced hyaluronic acid hydrogel composites in porcine cartilage defects. International Journal of Bioprinting, 9(5), 493-509. https://doi.org/10.18063/ijb.775

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

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",

author = "Galarraga, {Jonathan H.} and Zlotnick, {Hannah M.} and Locke, {Ryan C.} and Sachin Gupta and Fogarty, {Natalie L.} and Masada, {Kendall M.} and Stoeckl, {Brendan D.} and Lorielle Laforest and Miguel Castilho and Jos Malda and Riccardo Levato and Carey, {James L.} and Mauck, {Robert L.} and Burdick, {Jason A.}",

year = "2023",

doi = "10.18063/ijb.775",

language = "English",

volume = "9",

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Galarraga, JH, Zlotnick, HM, Locke, RC, Gupta, S, Fogarty, NL, Masada, KM, Stoeckl, BD, Laforest, L, Castilho, M, Malda, J, Levato, R, Carey, JL, Mauck, RL & Burdick, JA 2023, 'Evaluation of surgical fixation methods for the implantation of melt electrowriting-reinforced hyaluronic acid hydrogel composites in porcine cartilage defects', International Journal of Bioprinting, vol. 9, no. 5, pp. 493-509. https://doi.org/10.18063/ijb.775

Evaluation of surgical fixation methods for the implantation of melt electrowriting-reinforced hyaluronic acid hydrogel composites in porcine cartilage defects. / Galarraga, Jonathan H.; Zlotnick, Hannah M.; Locke, Ryan C. et al.
In: International Journal of Bioprinting, Vol. 9, No. 5, 2023, p. 493-509.

Research output: Contribution to journal › Article › Academic › peer-review

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T1 - Evaluation of surgical fixation methods for the implantation of melt electrowriting-reinforced hyaluronic acid hydrogel composites in porcine cartilage defects

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AU - Fogarty, Natalie L.

AU - Masada, Kendall M.

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AU - Laforest, Lorielle

AU - Castilho, Miguel

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AU - Levato, Riccardo

AU - Carey, James L.

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AU - Burdick, Jason A.

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

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