Evaluating the Efficacy of a Thermoresponsive Hydrogel for Delivering Anti-Collagen Antibodies to Reduce Posttraumatic Scarring in Orthopedic Tissues

Excessive posttraumatic scarring in orthopedic tissues, such as joint capsules, ligaments, tendons, muscles, and peripheral nerves, presents a significant medical problem, resulting in pain, restricted joint mobility, and impaired musculoskeletal function. Current treatments for excessive scarring a...

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Main Authors: Andrzej Steplewski, Jolanta Fertala, Lan Cheng, Mark L. Wang, Michael Rivlin, Pedro Beredjiklian, Andrzej Fertala
Format: Article
Language:English
Published: MDPI AG 2023-12-01
Series:Gels
Subjects:
Online Access:https://www.mdpi.com/2310-2861/9/12/971
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author Andrzej Steplewski
Jolanta Fertala
Lan Cheng
Mark L. Wang
Michael Rivlin
Pedro Beredjiklian
Andrzej Fertala
author_facet Andrzej Steplewski
Jolanta Fertala
Lan Cheng
Mark L. Wang
Michael Rivlin
Pedro Beredjiklian
Andrzej Fertala
author_sort Andrzej Steplewski
collection DOAJ
description Excessive posttraumatic scarring in orthopedic tissues, such as joint capsules, ligaments, tendons, muscles, and peripheral nerves, presents a significant medical problem, resulting in pain, restricted joint mobility, and impaired musculoskeletal function. Current treatments for excessive scarring are often ineffective and require the surgical removal of fibrotic tissue, which can aggravate the problem. The primary component of orthopedic scars is collagen I-rich fibrils. Our research team has developed a monoclonal anti-collagen antibody (ACA) that alleviates posttraumatic scarring by inhibiting collagen fibril formation. We previously established the safety and efficacy of ACA in a rabbit-based arthrofibrosis model. In this study, we evaluate the utility of a well-characterized thermoresponsive hydrogel (THG) as a delivery vehicle for ACA to injury sites. Crucial components of the hydrogel included N-isopropylacrylamide, poly(ethylene glycol) diacrylate, and hyaluronic acid. Our investigation focused on in vitro ACA release kinetics, stability, and activity. Additionally, we examined the antigen-binding characteristics of ACA post-release from the THG in an in vivo context. Our preliminary findings suggest that the THG construct exhibits promise as a delivery platform for antibody-based therapeutics to reduce excessive scarring in orthopedic tissues.
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spelling doaj.art-8b50bcc5bc314e0d8792833d10520fee2023-12-22T14:10:47ZengMDPI AGGels2310-28612023-12-0191297110.3390/gels9120971Evaluating the Efficacy of a Thermoresponsive Hydrogel for Delivering Anti-Collagen Antibodies to Reduce Posttraumatic Scarring in Orthopedic TissuesAndrzej Steplewski0Jolanta Fertala1Lan Cheng2Mark L. Wang3Michael Rivlin4Pedro Beredjiklian5Andrzej Fertala6Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USADepartment of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USADepartment of Neurosciences, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USADepartment of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USADepartment of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USADepartment of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USADepartment of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USAExcessive posttraumatic scarring in orthopedic tissues, such as joint capsules, ligaments, tendons, muscles, and peripheral nerves, presents a significant medical problem, resulting in pain, restricted joint mobility, and impaired musculoskeletal function. Current treatments for excessive scarring are often ineffective and require the surgical removal of fibrotic tissue, which can aggravate the problem. The primary component of orthopedic scars is collagen I-rich fibrils. Our research team has developed a monoclonal anti-collagen antibody (ACA) that alleviates posttraumatic scarring by inhibiting collagen fibril formation. We previously established the safety and efficacy of ACA in a rabbit-based arthrofibrosis model. In this study, we evaluate the utility of a well-characterized thermoresponsive hydrogel (THG) as a delivery vehicle for ACA to injury sites. Crucial components of the hydrogel included N-isopropylacrylamide, poly(ethylene glycol) diacrylate, and hyaluronic acid. Our investigation focused on in vitro ACA release kinetics, stability, and activity. Additionally, we examined the antigen-binding characteristics of ACA post-release from the THG in an in vivo context. Our preliminary findings suggest that the THG construct exhibits promise as a delivery platform for antibody-based therapeutics to reduce excessive scarring in orthopedic tissues.https://www.mdpi.com/2310-2861/9/12/971therapeutic antibodyfibrotic scarorthopedic tissuesthermoresponsive hydrogelperipheral nervearthrofibrosis
spellingShingle Andrzej Steplewski
Jolanta Fertala
Lan Cheng
Mark L. Wang
Michael Rivlin
Pedro Beredjiklian
Andrzej Fertala
Evaluating the Efficacy of a Thermoresponsive Hydrogel for Delivering Anti-Collagen Antibodies to Reduce Posttraumatic Scarring in Orthopedic Tissues
Gels
therapeutic antibody
fibrotic scar
orthopedic tissues
thermoresponsive hydrogel
peripheral nerve
arthrofibrosis
title Evaluating the Efficacy of a Thermoresponsive Hydrogel for Delivering Anti-Collagen Antibodies to Reduce Posttraumatic Scarring in Orthopedic Tissues
title_full Evaluating the Efficacy of a Thermoresponsive Hydrogel for Delivering Anti-Collagen Antibodies to Reduce Posttraumatic Scarring in Orthopedic Tissues
title_fullStr Evaluating the Efficacy of a Thermoresponsive Hydrogel for Delivering Anti-Collagen Antibodies to Reduce Posttraumatic Scarring in Orthopedic Tissues
title_full_unstemmed Evaluating the Efficacy of a Thermoresponsive Hydrogel for Delivering Anti-Collagen Antibodies to Reduce Posttraumatic Scarring in Orthopedic Tissues
title_short Evaluating the Efficacy of a Thermoresponsive Hydrogel for Delivering Anti-Collagen Antibodies to Reduce Posttraumatic Scarring in Orthopedic Tissues
title_sort evaluating the efficacy of a thermoresponsive hydrogel for delivering anti collagen antibodies to reduce posttraumatic scarring in orthopedic tissues
topic therapeutic antibody
fibrotic scar
orthopedic tissues
thermoresponsive hydrogel
peripheral nerve
arthrofibrosis
url https://www.mdpi.com/2310-2861/9/12/971
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