A Cell-free Biodegradable Synthetic Artificial Ligament for the Reconstruction of Anterior Cruciate Ligament in a Rat Model

Kawakami, Yoshiyuki; Nonaka, Kazuhiro; Fukase, Naomasa; Amore, Antonio D’; Murata, Yozo; Quinn, Patrick M.; Luketich, Samuel K.; Takayama, Koji; Patel, Kunj; Matsumoto, Tomoyuki; Cummins, James; Kurosaka, Masahiro; Kuroda, Ryosuke; Wagner, William R.; Fu, Freddie H.; Huard, Johnny

doi:10.1016/j.actbio.2020.10.037

Cited by 16 publications

(14 citation statements)

References 62 publications

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“…recent publications in the literature describing a variety of approaches to PU-based tendon and ligament scaffolds for reinforcement and regenerative repair. These have ranged from modifying PU mechanical properties, 174 increasing bioactivity with additives, 175 and even creating a graded functional scaffold for better integration in both bone and tendon tissue. 176 In a proof-of-concept study, Evrova et al 175 Given the inability of clinical and published pre-clinical treatments of tendon and ligament reconstruction to produce optimal functional recovery, new approaches are needed.…”

Section: Tendon/ligamentmentioning

confidence: 99%

“…Aside from the aforementioned, clinically available Artelon® PU, there have been several recent publications in the literature describing a variety of approaches to PU‐based tendon and ligament scaffolds for reinforcement and regenerative repair. These have ranged from modifying PU mechanical properties, 174 increasing bioactivity with additives, 175 and even creating a graded functional scaffold for better integration in both bone and tendon tissue 176 …”

Section: Pre‐clinical Applications Of Biodegradable Pu Scaffoldsmentioning

confidence: 99%

“…After 3 weeks, the coaxial electrospun tubes with PDGF‐BB showed a trend towards improvement in mechanical recovery. Using an electrospinning technique to concurrently spray cell culture medium while spinning, Kawakami et al 174 implanted PEUU scaffolds in a model of rat ACL reconstruction. This PEUU scaffold possessed more void space than a PEUU scaffold without concurrent cell culture medium spraying, allowing greater cell infiltration.…”

Section: Pre‐clinical Applications Of Biodegradable Pu Scaffoldsmentioning

confidence: 99%

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Biodegradable polyurethane scaffolds in regenerative medicine: Clinical translation review

Pedersen

Kim

Wagner

2022

J Biomedical Materials Res

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Early explorations of tissue engineering and regenerative medicine concepts commonly utilized simple polyesters such as polyglycolide, polylactide, and their copolymers as scaffolds. These biomaterials were deemed clinically acceptable, readily accessible, and provided processability and a generally known biological response. With experience and refinement of approaches, greater control of material properties and integrated bioactivity has received emphasis and a broadened palette of synthetic biomaterials has been employed. Biodegradable polyurethanes (PUs) have emerged as an attractive option for synthetic scaffolds in a variety of tissue applications because of their flexibility in molecular design and ability to fulfill mechanical property objectives, particularly in soft tissue applications. Biodegradable PUs are highly customizable based on their composition and processability to impart tailored mechanical and degradation behavior. Additionally, bioactive agents can be readily incorporated into these scaffolds to drive a desired biological response. Enthusiasm for biodegradable PU scaffolds has soared in recent years, leading to rapid growth in the literature documenting novel PU chemistries, scaffold designs, mechanical properties, and aspects of biocompatibility. Despite the enthusiasm in the field, there are still few examples of biodegradable PU scaffolds that have achieved regulatory approval and routine clinical use. However, there is a growing literature where biodegradable PU scaffolds are being specifically developed for a wide range of pathologies and where relevant pre‐clinical models are being employed. The purpose of this review is first to highlight examples of clinically used biodegradable PU scaffolds, and then to summarize the growing body of reports on pre‐clinical applications of biodegradable PU scaffolds.

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Section: Tendon/ligamentmentioning

confidence: 99%

Section: Pre‐clinical Applications Of Biodegradable Pu Scaffoldsmentioning

confidence: 99%

Section: Pre‐clinical Applications Of Biodegradable Pu Scaffoldsmentioning

confidence: 99%

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Biodegradable polyurethane scaffolds in regenerative medicine: Clinical translation review

Pedersen

Kim

Wagner

2022

J Biomedical Materials Res

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“…[37,38] Microfiber wires can also be adopted for tendon and ligament replacement in orthopedic surgery, chordae tendineae replacement and repair in cardiac surgery, and as suture materials for soft tissue injuries. While pre-clinical models support the potential of microfiber-based planar scaffolds for tendon and ligament engineering, [39] limited attempts have been made in duplicating the architecture of these anatomical structures at both the macro-and microscales. [13,40] In addition to the suture material applications discussed in this study, recent efforts are focused on modeling [41] and characterizing [42] atrioventricular heart valve chordal apparatus as well as improving chordae repair procedures.…”

Section: Discussionmentioning

confidence: 99%

Continuous Microfiber Wire Mandrel‐Less Biofabrication for Soft Tissue Engineering Applications

Adamo

Bartolacci

Pedersen

et al. 2022

Adv Healthcare Materials

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Suture materials are the most common bioimplants in surgical and clinical practice, playing a crucial role in wound healing and tendon and ligament repair. Despite the assortment available on the market, sutures are still affected by significant disadvantages, including failure in mimicking the mechanical properties of the tissue, excessive fibrosis, and inflammation. This study introduces a mandrel-less electrodeposition apparatus to fabricate continuous microfiber wires of indefinite length. The mandrel-less biofabrication produces wires, potentially used as medical fibers, with different microfiber bundles, that imitate the hierarchical organization of native tissues, and tailored mechanical properties. Microfiber wire morphology and mechanical properties are characterized by scanning electron microscopy, digital image processing, and uniaxial tensile test. Wires are tested in vitro on monocyte/macrophage stimulation and in vivo on a rat surgical wound model. The wires produced by mandrel-less deposition show an increased M2 macrophage phenotype in vitro. The in vivo assessment demonstrates that microfiber wires, compared to the medical fibers currently used, reduce pro-inflammatory macrophage response and preserve their mechanical properties after 30 days of use. These results make this microfiber wire an ideal candidate as a suture material for soft tissue surgery, suggesting a crucial role of microarchitecture in more favorable host response.

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“…Moreover, the development of various fabrication technologies such as solid free-form fabrication, fused deposition modeling, electrospinning nanofibers, etc., [ 17 , 18 , 19 ] have allowed the use of PCL for producing 3D scaffolds of various shapes and with customized inner architecture suiting a specific anatomical site. PCL is now widely studied in the engineering of bone [ 20 ], cartilage [ 21 ], tendons and ligaments [ 22 ], heart valves [ 23 ], blood vessels [ 24 ], nerves [ 25 ], and other tissues.…”

Section: Introductionmentioning

confidence: 99%

Modified Histopathological Protocol for Poly-ɛ-Caprolactone Scaffolds Preserving Their Trabecular, Honeycomb-like Structure

et al. 2022

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Poly-ɛ-caprolactone (PCL) is now widely studied in relation to the engineering of bone, cartilage, tendons, and other tissues. Standard histological protocols can destroy the carefully created trabecular and honeycomb-like architecture of PCL scaffolds, and could lead to scaffold fibers swelling, resulting in the displacement or compression of tissues inside the scaffold. The aim of this study was to modify a standard histopathological protocol for PCL scaffold preparation and evaluate it on porous cylindrical PCL scaffolds in a rat model. In 16 inbred Wag rats, 2 PCL scaffolds were implanted subcutaneously to both inguinal areas. Two months after implantation, harvested scaffolds were first subjected to μCT imaging, and then to histopathological analysis with standard (left inguinal area) and modified histopathological protocols (right inguinal area). To standardize the results, soft tissue percentages (STPs) were calculated on scaffold cross-sections obtained from both histopathological protocols and compared with corresponding µCT cross-sections. The modified protocol enabled the assessment of almost 10× more soft tissues on the scaffold cross-section than the standard procedure. Moreover, STP was only 1.5% lower than in the corresponding µCT cross-sections assessed before the histopathological procedure. The presented modification of the histopathological protocol is cheap, reproducible, and allows for a comprehensive evaluation of PCL scaffolds while maintaining their trabecular, honeycomb-like structure on cross-sections.

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A Cell-free Biodegradable Synthetic Artificial Ligament for the Reconstruction of Anterior Cruciate Ligament in a Rat Model

Cited by 16 publications

References 62 publications

Biodegradable polyurethane scaffolds in regenerative medicine: Clinical translation review

Biodegradable polyurethane scaffolds in regenerative medicine: Clinical translation review

Continuous Microfiber Wire Mandrel‐Less Biofabrication for Soft Tissue Engineering Applications

Modified Histopathological Protocol for Poly-ɛ-Caprolactone Scaffolds Preserving Their Trabecular, Honeycomb-like Structure

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