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^*, Jason A. Burdick^*

^*Corresponding author for this work

Regenerative Medicine and Stem Cells

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

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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
Article number	775
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

Keywords

Cartilage Repair
Fibrin Glue
Hydrogel
Melt electrowriting
Mesenchymal Stromal Cells

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775-2622-2-PBFinal published version, 4.05 MBLicence: CC BY

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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. Article 775. https://doi.org/10.18063/ijb.775

@article{6177d87badd84868a71dd815d717a884,

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.}",

note = "Funding Information: 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{\textquoteright} 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). Publisher Copyright: {\textcopyright} 2023 Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution License, permitting distribution, and reproduction in any medium, provided the original work is properly cited",

year = "2023",

doi = "10.18063/ijb.775",

language = "English",

volume = "9",

pages = "493--509",

number = "5",

}

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, 775, 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, 775, 2023, p. 493-509.

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

TY - JOUR

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

AU - Galarraga, Jonathan H.

AU - Zlotnick, Hannah M.

AU - Locke, Ryan C.

AU - Gupta, Sachin

AU - Fogarty, Natalie L.

AU - Masada, Kendall M.

AU - Stoeckl, Brendan D.

AU - Laforest, Lorielle

AU - Castilho, Miguel

AU - Malda, Jos

AU - Levato, Riccardo

AU - Carey, James L.

AU - Mauck, Robert L.

AU - Burdick, Jason A.

N1 - Funding Information: 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). Publisher Copyright: © 2023 Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution License, permitting distribution, and reproduction in any medium, provided the original work is properly cited

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - Cartilage Repair

KW - Fibrin Glue

KW - Hydrogel

KW - Melt electrowriting

KW - Mesenchymal Stromal Cells

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U2 - 10.18063/ijb.775

DO - 10.18063/ijb.775

M3 - Article

C2 - 37457945

AN - SCOPUS:85164082007

VL - 9

SP - 493

EP - 509

JO - International Journal of Bioprinting

JF - International Journal of Bioprinting

IS - 5

M1 - 775

ER -

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

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