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Toward a disruptive, minimally invasive small finger joint implant concept: cellular and molecular interactions with materials in vivo

Toward a disruptive, minimally invasive small finger joint implant concept: cellular and molecular interactions with materials in vivo
Toward a disruptive, minimally invasive small finger joint implant concept: cellular and molecular interactions with materials in vivo

Osteoarthritis (OA) poses significant therapeutic challenges, particularly OA that affects the hand. Currently available treatment strategies are often limited in terms of their efficacy in managing pain, regulating invasiveness, and restoring joint function. The APRICOT implant system developed by Aurora Medical Ltd (Chichester, UK) introduces a minimally invasive, bone-conserving approach for treating hand OA (https://apricot-project.eu/). By utilizing polycarbonate urethane (PCU), this implant incorporates a caterpillar track-inspired design to promote the restoration of natural movement to the joint. Surface modifications of PCU have been proposed for the biological fixation of the implant. This study investigated the biocompatibility of PCU alone or in combination with two surface modifications, namely dopamine-carboxymethylcellulose (dCMC) and calcium-phosphate (CaP) coatings. In a rat soft tissue model, native and CaP-coated PCU foils did not increase cellular migration or cytotoxicity at the implant–soft tissue interface after 3 d, showing gene expression of proinflammatory cytokines similar to that in non-implanted sham sites. However, dCMC induced an amplified initial inflammatory response that was characterized by increased chemotaxis and cytotoxicity, as well as pronounced gene activation of proinflammatory macrophages and neoangiogenesis. By 21 d, inflammation subsided in all the groups, allowing for implant encapsulation. In a rat bone model, 6 d and 28 d after release of the periosteum, all implant types were adapted to the bone surface with a surrounding fibrous capsule and no protracted inflammatory response was observed. These findings demonstrated the biocompatibility of native and CaP-coated PCU foils as components of APRICOT implants. Statement of significance: Hand osteoarthritis treatments require materials that minimize irritation of the delicate finger joints. Differing from existing treatments, the APRICOT implant leverages polycarbonate urethane (PCU) for minimally invasive joint replacement. This interdisciplinary, preclinical study investigated the biocompatibility of thin polycarbonate urethane (PCU) foils and their surface modifications with calcium-phosphate (CaP) or dopamine-carboxymethylcellulose (dCMC). Cellular and morphological analyses revealed that both native and Ca-P coated PCU elicit transient inflammation, similar to sham sites, and a thin fibrous encapsulation in soft tissues and on bone surfaces. However, dCMC surface modification amplified initial chemotaxis and cytotoxicity, with pronounced activation of proinflammatory and neoangiogenesis genes. Therefore, native and CaP-coated PCU possess sought-for biocompatible properties, crucial for patient safety and performance of APRICOT implant.

Animal models, Biocompatibility, Gene expression, Osteoarthritis, Polyurethanes
1742-7061
130-145
Ben-Amara, Heithem
436b2bfb-2867-45e7-ab66-3528470a408f
Farjam, Pardis
66fce58a-bbb7-483f-9689-0941dca57a74
Lutz, Theresa M.
323ce42a-34dd-4ba6-8885-5439a0de5961
Omar, Omar
287d44d6-d240-4de3-8e2f-a8adf770220c
Palmquist, Anders
d0176078-cfc0-4bd8-9213-127003a6ee52
Lieleg, Oliver
90cb3d33-1402-4475-af9f-86a05d095102
Browne, Martin
6578cc37-7bd6-43b9-ae5c-77ccb7726397
Taylor, Andrew
dd713dc1-7bd3-40a0-b645-83397c61dcf5
Verkerke, Gijsbertus J.
e35866f3-67df-4edc-bcdf-a2e47d8a0a45
Rouwkema, Jeroen
0a774b5b-dcad-4c77-a5be-f6388270b791
Thomsen, Peter
fc7084ed-7b98-4f90-82c2-3879b3e8788c
Ben-Amara, Heithem
436b2bfb-2867-45e7-ab66-3528470a408f
Farjam, Pardis
66fce58a-bbb7-483f-9689-0941dca57a74
Lutz, Theresa M.
323ce42a-34dd-4ba6-8885-5439a0de5961
Omar, Omar
287d44d6-d240-4de3-8e2f-a8adf770220c
Palmquist, Anders
d0176078-cfc0-4bd8-9213-127003a6ee52
Lieleg, Oliver
90cb3d33-1402-4475-af9f-86a05d095102
Browne, Martin
6578cc37-7bd6-43b9-ae5c-77ccb7726397
Taylor, Andrew
dd713dc1-7bd3-40a0-b645-83397c61dcf5
Verkerke, Gijsbertus J.
e35866f3-67df-4edc-bcdf-a2e47d8a0a45
Rouwkema, Jeroen
0a774b5b-dcad-4c77-a5be-f6388270b791
Thomsen, Peter
fc7084ed-7b98-4f90-82c2-3879b3e8788c

Ben-Amara, Heithem, Farjam, Pardis, Lutz, Theresa M., Omar, Omar, Palmquist, Anders, Lieleg, Oliver, Browne, Martin, Taylor, Andrew, Verkerke, Gijsbertus J., Rouwkema, Jeroen and Thomsen, Peter (2024) Toward a disruptive, minimally invasive small finger joint implant concept: cellular and molecular interactions with materials in vivo. Acta Biomaterialia, 183, 130-145. (doi:10.1016/j.actbio.2024.05.042).

Record type: Article

Abstract

Osteoarthritis (OA) poses significant therapeutic challenges, particularly OA that affects the hand. Currently available treatment strategies are often limited in terms of their efficacy in managing pain, regulating invasiveness, and restoring joint function. The APRICOT implant system developed by Aurora Medical Ltd (Chichester, UK) introduces a minimally invasive, bone-conserving approach for treating hand OA (https://apricot-project.eu/). By utilizing polycarbonate urethane (PCU), this implant incorporates a caterpillar track-inspired design to promote the restoration of natural movement to the joint. Surface modifications of PCU have been proposed for the biological fixation of the implant. This study investigated the biocompatibility of PCU alone or in combination with two surface modifications, namely dopamine-carboxymethylcellulose (dCMC) and calcium-phosphate (CaP) coatings. In a rat soft tissue model, native and CaP-coated PCU foils did not increase cellular migration or cytotoxicity at the implant–soft tissue interface after 3 d, showing gene expression of proinflammatory cytokines similar to that in non-implanted sham sites. However, dCMC induced an amplified initial inflammatory response that was characterized by increased chemotaxis and cytotoxicity, as well as pronounced gene activation of proinflammatory macrophages and neoangiogenesis. By 21 d, inflammation subsided in all the groups, allowing for implant encapsulation. In a rat bone model, 6 d and 28 d after release of the periosteum, all implant types were adapted to the bone surface with a surrounding fibrous capsule and no protracted inflammatory response was observed. These findings demonstrated the biocompatibility of native and CaP-coated PCU foils as components of APRICOT implants. Statement of significance: Hand osteoarthritis treatments require materials that minimize irritation of the delicate finger joints. Differing from existing treatments, the APRICOT implant leverages polycarbonate urethane (PCU) for minimally invasive joint replacement. This interdisciplinary, preclinical study investigated the biocompatibility of thin polycarbonate urethane (PCU) foils and their surface modifications with calcium-phosphate (CaP) or dopamine-carboxymethylcellulose (dCMC). Cellular and morphological analyses revealed that both native and Ca-P coated PCU elicit transient inflammation, similar to sham sites, and a thin fibrous encapsulation in soft tissues and on bone surfaces. However, dCMC surface modification amplified initial chemotaxis and cytotoxicity, with pronounced activation of proinflammatory and neoangiogenesis genes. Therefore, native and CaP-coated PCU possess sought-for biocompatible properties, crucial for patient safety and performance of APRICOT implant.

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Accepted/In Press date: 24 May 2024
e-pub ahead of print date: 28 May 2024
Published date: 15 July 2024
Additional Information: Publisher Copyright: © 2024 The Author(s)
Keywords: Animal models, Biocompatibility, Gene expression, Osteoarthritis, Polyurethanes

Identifiers

Local EPrints ID: 490768
URI: http://eprints.soton.ac.uk/id/eprint/490768
ISSN: 1742-7061
PURE UUID: 0d469884-40b3-4511-ba61-303d42a572fb
ORCID for Martin Browne: ORCID iD orcid.org/0000-0001-5184-050X

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Date deposited: 06 Jun 2024 16:39
Last modified: 20 Jul 2024 01:35

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Contributors

Author: Heithem Ben-Amara
Author: Pardis Farjam
Author: Theresa M. Lutz
Author: Omar Omar
Author: Anders Palmquist
Author: Oliver Lieleg
Author: Martin Browne ORCID iD
Author: Andrew Taylor
Author: Gijsbertus J. Verkerke
Author: Jeroen Rouwkema
Author: Peter Thomsen

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