Eur. Pol. J. 176, 111386 (2022)

Ayman El Jundi, Matthias Mayor, Enrique Folgado, Chaimaa Gomri, Belkacem Tarek Benkhaled, Arnaud Chaix, Pascal Verdie, Benjamin Nottelet, Mona Semsarilar

ABSTRACT

Biodegradable poly(ethylene glycol)-b-poly(ε-caprolactone-g-peptide) (PEG-b-PCL-g-peptide) copolymers were synthesized using a combination of ring opening  polymerization and thiol-yne photoaddition of peptides on the alkyne functional PCL block. The peptides Phe-Phe, Tyr-Tyr and Arg-Gly-Asp were selected based on the expected interactions (Pi-stacking, H-bonding, electrostatic). The self-assembly of these copolymers was studied via testing the effect of various parameters such as the nature of the solvent and non-solvant as well as their ratio,mixing method, temperature and concentration. Structures obtained by varying these parameters were characterised using transmission electron microscopy (TEM) and dynamic light scattering (DLS). Spherical and lamellar structures (oval leaf-shaped) of different sizes were identified as a function of the conditions. The role of the crystallisation and of the peptides was highlighted with more defined and stable structures obtained for Tyr-Tyr functional copolymers.

Chem. Eur. J. 10.1002/chem.202001571

Ahmad Mehdi, Martin Julie, Mohammad Wehbi, Cecile Echalier, Sylvie hunger, Audrey Bethry, Xavier garric, coline Pinese, jean Martinez, Lubomir vezenkov, and gilles subra

Eur. Polym. J. 2020, 135, 109886.

Said Jebors*, Coline Pinese*, Titouan Montheil*, Audrey Bethry, Simon Verquin, Louise Plais, Marie Moulin, Chloé Dupont, Xavier Garric, Ahmad Mehdi, Jean Martinez, Gilles Subra

Materials Today Chemistry 4, 73–83 (2017)

Pinese, C., Jebors, S., Stoebner, P. E., Humblot, V., Verdié, P., Causse, L., Garric, X., Taillades, H., Martinez, J., Mehdi, A. & Subra, G

Journal of Materials Science: Materials in Medicine (2016), 27(9), 1-10

Yala,S., Boustta,M; Gallet, O; Hindie, M; Carreiras, F; Benachour, H; Sidane, D; Khireddine, H.

Mat. Sci. Eng. C-Mater. Biol. Appl. 48, 457–468 (2015)

Basile, M. A., d’Ayala, G. G., Malinconico, M., Laurienzo, P., Coudane, J., Nottelet, B., Della Ragione, F. & Oliva, A.

Biomat. Sci. 9, 6203–6213 (2021)

 Awada H., Seene S., Laurencin D., Lemaire L., Franconi F., Bernex F., Bethry A., Garric X., Guari Y., Nottelet B.

ABSTRACT

There is a growing interest in magnetic nanocomposites in biomaterials science. In particular, nanocomposites that combine poly(lactide) (PLA) nanofibers and super paramagnetic iron oxide nanoparticles (SPIONs), which can be obtained by either electrospinning of a SPIONs suspension in PLA or by precipitating SPIONs at the surface of PLA, are well documented in the literature. However, these two classical processes yield nanocomposites with altered materials properties, and their long-term in vivo fate and performances have in most cases only been evaluated over short periods of time. Recently, we reported a new strategy to prepare well-defined PLA@SPIONs nanofibers with a quasi-monolayer of SPIONs anchored at the surface of PLA electrospun fibers. Herein, we report on a 6-month in vivo rat implantation study with the aim of evaluating the long-term magnetic resonance imaging (MRI) properties of this new class of magnetic nanocomposites, as well as their tissue integration and degradation. Using clinically relevant T2-weighted MRI conditions, we show that the PLA@SPIONs nanocomposites are clearly visible up to 6 months. We also evaluate here by histological analyses the slow degradation of the PLA@SPIONs, as well as their biocompatibility. Overall, these results make these nanocomposites attractive for the development of magnetic biomaterials for biomedical applications.

Acta Biomaterialia 131, 302–313 (2021)

Funnell J.L., Ziemba A.M., Nowak J.F., Awada H., Prokopiou N., Samuel J., Guari Y., Nottelet B., Gilbert R.J.

ABSTRACT

Magnetic fiber composites combining superparamagnetic iron oxide nanoparticles (SPIONs) and electrospun fibers have shown promise in tissue engineering fields. Controlled grafting of SPIONs to the fibers post-electrospinning generates biocompatible magnetic composites without altering desired fiber morphology. Here, for the first time, we assess the potential of SPION-grafted scaffolds combined with magnetic fields to promote neurite outgrowth by providing contact guidance from the aligned fibers and mechanical stimulation from the SPIONs in the magnetic field. Neurite outgrowth from primary rat dorsal root ganglia (DRG) was assessed from explants cultured on aligned control and SPION-grafted electrospun fibers as well as on non-grafted fibers with SPIONs dispersed in the culture media. To determine the optimal magnetic field stimulation to promote neurite outgrowth, we generated a static, alternating, and linearly moving magnet and simulated the magnetic flux density at different areas of the scaffold over time. The alternating magnetic field increased neurite length by 40% on control fibers compared to a static magnetic field. Additionally, stimulation with an alternating magnetic field resulted in a 30% increase in neurite length and 62% increase in neurite area on SPION-grafted fibers compared to DRG cultured on PLLA fibers with untethered SPIONs added to the culture media. These findings demonstrate that SPION-grafted fiber composites in combination with magnetic fields are more beneficial for stimulating neurite outgrowth on electrospun fibers than dispersed SPIONs.

ACS Appl. Mater. Interfaces 11, 9519–9529 (2019)

Awada H., Al Samad A., Laurencin D., Gilbert R., Dumail X., El Jundi A., Bethry A., Pomrenke R., Johnson C., Lemaire L., Franconi F., Félix G., Larionova J., Guari Y., Nottelet B.

ABSTRACT

Composites combining superparamagnetic iron oxide nanoparticles (SPIONs) and polymers are largely present in modern (bio)materials. However, while SPIONs embedded in polymer matrices are classically reported, the mechanical and degradation properties of the polymer scaffold are impacted by the SPIONs. Therefore, the controlled anchoring of SPIONs onto polymer surfaces is still a major challenge. Herein, we propose an efficient strategy for the direct and uniform anchoring of SPIONs on the surface of functionalized-polylactide (PLA) nanofibers via a simple free ligand exchange procedure to design PLA@SPIONs core@shell nanocomposites. The resulting PLA@SPIONs hybrid biomaterials are characterized by electron microscopy (SEM and TEM) and EDXS analysis, to probe the morphology and detect elements present at the organic/inorganic interface, respectively. A monolayer of SPIONs with a complete and homogeneous coverage is observed on the surface of PLA nanofibers. Magnetization experiments show that magnetic properties of the nanoparticles are well-preserved after their grafting on the PLA fibers and that the size of the nanoparticles does not change. The absence of cytotoxicity, combined with a high sensitivity of detection in MRI both in vitro and in vivo make these hybrid nanocomposites attractive for the development of magnetic biomaterials for biomedical applications.

Adv. Mater. Interf. 2300066 (2023)

Mathilde Grosjean, Lucien Guth, Stéphane Déjean, Cédric Paniagua, Benjamin Nottelet

ABSTRACT

Self-healable degradable networks encounter a growing popularity for biomedical applications due to their ability to recover their properties after damage. Self-healable hydrogels dominate with applications in tissue engineering and drug delivery. On the opposite and despite their potential for medical devices, self-healable elastomers remain scarce, especially if they must be compatible with fused deposition modeling (FDM) 3D-printing and self-heal at physiological temperature under hydrated state. These unmet challenges are addressed in this work with degradable elastomeric networks based on dynamic imine bonds prepared from multi(aldehyde) and multi(amine) hydrophobic PEG-PLA star-shaped copolymers. The star topology of these copolymers is the key feature of our strategy as it allows the design of multifunctional high molecular weights pre-polymers that ensure an efficient dynamic chemical crosslinking while guarantying access to the FDM process generally restricted to thermoplastics. The proposed elastomeric networks combine high self-healing efficiencies at 37°C (> 97 %) with mechanical properties compatible with soft tissues and a linear degradation profile. Their FDM processing to produce self-healable tubular devices is demonstrated. Finally, their cytocompatibility is assessed and confirm their potential as biodegradable elastomeric networks to be used for the design of self-healable 3D-printed devices for biomedical applications.

Biomacromolecules 24,3472–3483 (2023)

Mathilde Grosjean, Dimitri Berne, Sylvain Caillol, Vincent Ladmiral, Benjamin Nottelet

ABSTRACT

The development of dynamic covalent chemistry opens the way to the design of materials able to be reprocessed by an internal exchange reaction under thermal stimulus. Imine exchange differs from other exchange reactions by its relatively low temperature of activation. In this study, amine-functionalized star-shaped PEG–PLA and an aldehyde-functionalized hydroxyurethane modifier were combined to produce PEG–PLA/hydroxyurethane networks incorporating imine bonds. The thermal and mechanical properties of these new materials were evaluated as a function of the initial ratio of amine/aldehyde used during synthesis. Rheological analyses highlighted the dynamic behavior of these vitrimers at moderate temperature (60–85 °C) and provided the flow activation energies. Additionally, the reprocessability of these PEG–PLA/hydroxyurethane vitrimers was assessed by comparing the material properties before reshaping and after three reprocessing cycles (1 ton, 1 h, 70 °C). Hence, these materials can easily be designed to satisfy a specific medical application without properties loss. This work opens the way to the development of a new generation of dynamic materials combining degradable PEG–PLA copolymers and hydroxyurethane modifiers, which could find applications in the shape of medical devices on-demand under mild conditions.

Adv. Funct. Mater 2205315 (2023)

Mathilde Grosjean, Louis Gangolphe, Benjamin Nottelet

ABSTRACT

Among biomaterials, 3D networks with capacities to absorb and retain large quantities of water (hydrogels) or withstand significant deformation and stress while recovering their initial structures at rest (elastomers) are largely used in biomedical applications. However, when damaged, they cannot recover their initial structures and properties. To overcome this limitation and satisfy the requirements of the biomedical field, self-healable hydrogels and

elastomers designed using (bio)degradable or bioeliminable polymer chains have been developed and are becoming increasingly popular. This review presents the latest advances in the field of self-healing degradable/bioeliminable networks designed for use in health applications. The strategies used to develop such networks based on reversible covalent or physical cross-linking or their combination via dual/multi-cross-linking approaches are analyzed in detail. The key parameters of these hydrogels and elastomers, such as mechanical properties, repair and degradation times, and healing efficiencies, are critically considered in terms of their suitabilities in biomedical applications. Finally, their current and prospective uses as biomaterials in the fields of tissue engineering, drug/cell delivery, and medical devices are presented, followed by the remaining challenges faced to ensure the further success of degradable self-healable networks.

ACS Appl. Mater. Interfaces 15, 2077-2091 (2023)

Mathilde Grosjean, Louis Gangolphe, Stéphane Dejean, Sylvie Hunger, Audrey Bethry, Frédéric Bossard, Xavier Garric, Benjamin Nottelet

ABSTRACT

In the biomedical field, degradable chemically crosslinked elastomers are interesting materials for tissue engineering applications since they present rubber-like mechanical properties matching with those of soft tissues and are able to preserve their 3D structure over degradation. Their use in biomedical applications requires surgical handling and implantation that can be source of accidental damages responsible for loss of properties. Therefore, their inability to be healed after damage or breaking can be a major drawback. In this work, biodegradable dual-crosslinked networks that exhibit fast and efficient self-healing properties at 37 °C are designed. Self-healable dual-crosslinked (chemically and physically) elastomeric networks are prepared from two methods. The first approach is based on the mix of hydrophobic PEG-PLA star-shaped copolymers functionalized either with catechol or methacrylate moieties. In the second approach, hydrophobic bifunctional PEG-PLA star-shaped copolymers with both catechol and methacrylate on their structure are used. In the two systems the supramolecular network is responsible for the self-healing properties thanks to the dynamic dissociation/re-association of the numerous hydrogen bonds between the catechol groups, whereas the covalent network ensures mechanical properties similar to pure methacrylate networks. The self-healable materials display mechanical properties that are compatible with soft tissues and exhibit linear degradation because of the chemical crosslinks. The performances of networks from mix copolymers vs. bifunctional copolymers are compared and demonstrate the superiority of the later. The biocompatibility of the materials is also demonstrated and confirm the potential of these degradable self-healable elastomeric networks to be used for the design of temporary medical devices.

Adv. Mater. Interf. 2300066 (2023)

Mathilde Grosjean, Lucien Guth, Stéphane Déjean, Cédric Paniagua, Benjamin Nottelet

ABSTRACT

Self-healable degradable networks encounter a growing popularity for biomedical applications due to their ability to recover their properties after damage. Self-healable hydrogels dominate with applications in tissue engineering and drug delivery. On the opposite and despite their potential for medical devices, self-healable elastomers remain scarce, especially if they must be compatible with fused deposition modeling (FDM) 3D-printing and self-heal at physiological temperature under hydrated state. These unmet challenges are addressed in this work with degradable elastomeric networks based on dynamic imine bonds prepared from multi(aldehyde) and multi(amine) hydrophobic PEG-PLA star-shaped copolymers. The star topology of these copolymers is the key feature of our strategy as it allows the design of multifunctional high molecular weights pre-polymers that ensure an efficient dynamic chemical crosslinking while guarantying access to the FDM process generally restricted to thermoplastics. The proposed elastomeric networks combine high self-healing efficiencies at 37°C (> 97 %) with mechanical properties compatible with soft tissues and a linear degradation profile. Their FDM processing to produce self-healable tubular devices is demonstrated. Finally, their cytocompatibility is assessed and confirm their potential as biodegradable elastomeric networks to be used for the design of self-healable 3D-printed devices for biomedical applications.

Biomacromolecules 24,3472–3483 (2023)

Mathilde Grosjean, Dimitri Berne, Sylvain Caillol, Vincent Ladmiral, Benjamin Nottelet

ABSTRACT

The development of dynamic covalent chemistry opens the way to the design of materials able to be reprocessed by an internal exchange reaction under thermal stimulus. Imine exchange differs from other exchange reactions by its relatively low temperature of activation. In this study, amine-functionalized star-shaped PEG–PLA and an aldehyde-functionalized hydroxyurethane modifier were combined to produce PEG–PLA/hydroxyurethane networks incorporating imine bonds. The thermal and mechanical properties of these new materials were evaluated as a function of the initial ratio of amine/aldehyde used during synthesis. Rheological analyses highlighted the dynamic behavior of these vitrimers at moderate temperature (60–85 °C) and provided the flow activation energies. Additionally, the reprocessability of these PEG–PLA/hydroxyurethane vitrimers was assessed by comparing the material properties before reshaping and after three reprocessing cycles (1 ton, 1 h, 70 °C). Hence, these materials can easily be designed to satisfy a specific medical application without properties loss. This work opens the way to the development of a new generation of dynamic materials combining degradable PEG–PLA copolymers and hydroxyurethane modifiers, which could find applications in the shape of medical devices on-demand under mild conditions.

Adv. Funct. Mater 2205315 (2023)

Mathilde Grosjean, Louis Gangolphe, Benjamin Nottelet

ABSTRACT

Among biomaterials, 3D networks with capacities to absorb and retain large quantities of water (hydrogels) or withstand significant deformation and stress while recovering their initial structures at rest (elastomers) are largely used in biomedical applications. However, when damaged, they cannot recover their initial structures and properties. To overcome this limitation and satisfy the requirements of the biomedical field, self-healable hydrogels and

elastomers designed using (bio)degradable or bioeliminable polymer chains have been developed and are becoming increasingly popular. This review presents the latest advances in the field of self-healing degradable/bioeliminable networks designed for use in health applications. The strategies used to develop such networks based on reversible covalent or physical cross-linking or their combination via dual/multi-cross-linking approaches are analyzed in detail. The key parameters of these hydrogels and elastomers, such as mechanical properties, repair and degradation times, and healing efficiencies, are critically considered in terms of their suitabilities in biomedical applications. Finally, their current and prospective uses as biomaterials in the fields of tissue engineering, drug/cell delivery, and medical devices are presented, followed by the remaining challenges faced to ensure the further success of degradable self-healable networks.

ACS Appl. Mater. Interfaces 15, 2077-2091 (2023)

Mathilde Grosjean, Louis Gangolphe, Stéphane Dejean, Sylvie Hunger, Audrey Bethry, Frédéric Bossard, Xavier Garric, Benjamin Nottelet

ABSTRACT

In the biomedical field, degradable chemically crosslinked elastomers are interesting materials for tissue engineering applications since they present rubber-like mechanical properties matching with those of soft tissues and are able to preserve their 3D structure over degradation. Their use in biomedical applications requires surgical handling and implantation that can be source of accidental damages responsible for loss of properties. Therefore, their inability to be healed after damage or breaking can be a major drawback. In this work, biodegradable dual-crosslinked networks that exhibit fast and efficient self-healing properties at 37 °C are designed. Self-healable dual-crosslinked (chemically and physically) elastomeric networks are prepared from two methods. The first approach is based on the mix of hydrophobic PEG-PLA star-shaped copolymers functionalized either with catechol or methacrylate moieties. In the second approach, hydrophobic bifunctional PEG-PLA star-shaped copolymers with both catechol and methacrylate on their structure are used. In the two systems the supramolecular network is responsible for the self-healing properties thanks to the dynamic dissociation/re-association of the numerous hydrogen bonds between the catechol groups, whereas the covalent network ensures mechanical properties similar to pure methacrylate networks. The self-healable materials display mechanical properties that are compatible with soft tissues and exhibit linear degradation because of the chemical crosslinks. The performances of networks from mix copolymers vs. bifunctional copolymers are compared and demonstrate the superiority of the later. The biocompatibility of the materials is also demonstrated and confirm the potential of these degradable self-healable elastomeric networks to be used for the design of temporary medical devices.

Adv. Mater. Interf. 2300066 (2023)

Mathilde Grosjean, Lucien Guth, Stéphane Déjean, Cédric Paniagua, Benjamin Nottelet

ABSTRACT

Self-healable degradable networks encounter a growing popularity for biomedical applications due to their ability to recover their properties after damage. Self-healable hydrogels dominate with applications in tissue engineering and drug delivery. On the opposite and despite their potential for medical devices, self-healable elastomers remain scarce, especially if they must be compatible with fused deposition modeling (FDM) 3D-printing and self-heal at physiological temperature under hydrated state. These unmet challenges are addressed in this work with degradable elastomeric networks based on dynamic imine bonds prepared from multi(aldehyde) and multi(amine) hydrophobic PEG-PLA star-shaped copolymers. The star topology of these copolymers is the key feature of our strategy as it allows the design of multifunctional high molecular weights pre-polymers that ensure an efficient dynamic chemical crosslinking while guarantying access to the FDM process generally restricted to thermoplastics. The proposed elastomeric networks combine high self-healing efficiencies at 37°C (> 97 %) with mechanical properties compatible with soft tissues and a linear degradation profile. Their FDM processing to produce self-healable tubular devices is demonstrated. Finally, their cytocompatibility is assessed and confirm their potential as biodegradable elastomeric networks to be used for the design of self-healable 3D-printed devices for biomedical applications.

Biomacromolecules 24,3472–3483 (2023)

Mathilde Grosjean, Dimitri Berne, Sylvain Caillol, Vincent Ladmiral, Benjamin Nottelet

ABSTRACT

The development of dynamic covalent chemistry opens the way to the design of materials able to be reprocessed by an internal exchange reaction under thermal stimulus. Imine exchange differs from other exchange reactions by its relatively low temperature of activation. In this study, amine-functionalized star-shaped PEG–PLA and an aldehyde-functionalized hydroxyurethane modifier were combined to produce PEG–PLA/hydroxyurethane networks incorporating imine bonds. The thermal and mechanical properties of these new materials were evaluated as a function of the initial ratio of amine/aldehyde used during synthesis. Rheological analyses highlighted the dynamic behavior of these vitrimers at moderate temperature (60–85 °C) and provided the flow activation energies. Additionally, the reprocessability of these PEG–PLA/hydroxyurethane vitrimers was assessed by comparing the material properties before reshaping and after three reprocessing cycles (1 ton, 1 h, 70 °C). Hence, these materials can easily be designed to satisfy a specific medical application without properties loss. This work opens the way to the development of a new generation of dynamic materials combining degradable PEG–PLA copolymers and hydroxyurethane modifiers, which could find applications in the shape of medical devices on-demand under mild conditions.

Adv. Funct. Mater 2205315 (2023)

Mathilde Grosjean, Louis Gangolphe, Benjamin Nottelet

ABSTRACT

Among biomaterials, 3D networks with capacities to absorb and retain large quantities of water (hydrogels) or withstand significant deformation and stress while recovering their initial structures at rest (elastomers) are largely used in biomedical applications. However, when damaged, they cannot recover their initial structures and properties. To overcome this limitation and satisfy the requirements of the biomedical field, self-healable hydrogels and

elastomers designed using (bio)degradable or bioeliminable polymer chains have been developed and are becoming increasingly popular. This review presents the latest advances in the field of self-healing degradable/bioeliminable networks designed for use in health applications. The strategies used to develop such networks based on reversible covalent or physical cross-linking or their combination via dual/multi-cross-linking approaches are analyzed in detail. The key parameters of these hydrogels and elastomers, such as mechanical properties, repair and degradation times, and healing efficiencies, are critically considered in terms of their suitabilities in biomedical applications. Finally, their current and prospective uses as biomaterials in the fields of tissue engineering, drug/cell delivery, and medical devices are presented, followed by the remaining challenges faced to ensure the further success of degradable self-healable networks.

ACS Appl. Mater. Interfaces 15, 2077-2091 (2023)

Mathilde Grosjean, Louis Gangolphe, Stéphane Dejean, Sylvie Hunger, Audrey Bethry, Frédéric Bossard, Xavier Garric, Benjamin Nottelet

ABSTRACT

In the biomedical field, degradable chemically crosslinked elastomers are interesting materials for tissue engineering applications since they present rubber-like mechanical properties matching with those of soft tissues and are able to preserve their 3D structure over degradation. Their use in biomedical applications requires surgical handling and implantation that can be source of accidental damages responsible for loss of properties. Therefore, their inability to be healed after damage or breaking can be a major drawback. In this work, biodegradable dual-crosslinked networks that exhibit fast and efficient self-healing properties at 37 °C are designed. Self-healable dual-crosslinked (chemically and physically) elastomeric networks are prepared from two methods. The first approach is based on the mix of hydrophobic PEG-PLA star-shaped copolymers functionalized either with catechol or methacrylate moieties. In the second approach, hydrophobic bifunctional PEG-PLA star-shaped copolymers with both catechol and methacrylate on their structure are used. In the two systems the supramolecular network is responsible for the self-healing properties thanks to the dynamic dissociation/re-association of the numerous hydrogen bonds between the catechol groups, whereas the covalent network ensures mechanical properties similar to pure methacrylate networks. The self-healable materials display mechanical properties that are compatible with soft tissues and exhibit linear degradation because of the chemical crosslinks. The performances of networks from mix copolymers vs. bifunctional copolymers are compared and demonstrate the superiority of the later. The biocompatibility of the materials is also demonstrated and confirm the potential of these degradable self-healable elastomeric networks to be used for the design of temporary medical devices.

Adv. Mater. Interf. 2300066 (2023)

Mathilde Grosjean, Lucien Guth, Stéphane Déjean, Cédric Paniagua, Benjamin Nottelet

ABSTRACT

Self-healable degradable networks encounter a growing popularity for biomedical applications due to their ability to recover their properties after damage. Self-healable hydrogels dominate with applications in tissue engineering and drug delivery. On the opposite and despite their potential for medical devices, self-healable elastomers remain scarce, especially if they must be compatible with fused deposition modeling (FDM) 3D-printing and self-heal at physiological temperature under hydrated state. These unmet challenges are addressed in this work with degradable elastomeric networks based on dynamic imine bonds prepared from multi(aldehyde) and multi(amine) hydrophobic PEG-PLA star-shaped copolymers. The star topology of these copolymers is the key feature of our strategy as it allows the design of multifunctional high molecular weights pre-polymers that ensure an efficient dynamic chemical crosslinking while guarantying access to the FDM process generally restricted to thermoplastics. The proposed elastomeric networks combine high self-healing efficiencies at 37°C (> 97 %) with mechanical properties compatible with soft tissues and a linear degradation profile. Their FDM processing to produce self-healable tubular devices is demonstrated. Finally, their cytocompatibility is assessed and confirm their potential as biodegradable elastomeric networks to be used for the design of self-healable 3D-printed devices for biomedical applications.

Biomacromolecules 24,3472–3483 (2023)

Mathilde Grosjean, Dimitri Berne, Sylvain Caillol, Vincent Ladmiral, Benjamin Nottelet

ABSTRACT

The development of dynamic covalent chemistry opens the way to the design of materials able to be reprocessed by an internal exchange reaction under thermal stimulus. Imine exchange differs from other exchange reactions by its relatively low temperature of activation. In this study, amine-functionalized star-shaped PEG–PLA and an aldehyde-functionalized hydroxyurethane modifier were combined to produce PEG–PLA/hydroxyurethane networks incorporating imine bonds. The thermal and mechanical properties of these new materials were evaluated as a function of the initial ratio of amine/aldehyde used during synthesis. Rheological analyses highlighted the dynamic behavior of these vitrimers at moderate temperature (60–85 °C) and provided the flow activation energies. Additionally, the reprocessability of these PEG–PLA/hydroxyurethane vitrimers was assessed by comparing the material properties before reshaping and after three reprocessing cycles (1 ton, 1 h, 70 °C). Hence, these materials can easily be designed to satisfy a specific medical application without properties loss. This work opens the way to the development of a new generation of dynamic materials combining degradable PEG–PLA copolymers and hydroxyurethane modifiers, which could find applications in the shape of medical devices on-demand under mild conditions.

Adv. Funct. Mater 2205315 (2023)

Mathilde Grosjean, Louis Gangolphe, Benjamin Nottelet

ABSTRACT

Among biomaterials, 3D networks with capacities to absorb and retain large quantities of water (hydrogels) or withstand significant deformation and stress while recovering their initial structures at rest (elastomers) are largely used in biomedical applications. However, when damaged, they cannot recover their initial structures and properties. To overcome this limitation and satisfy the requirements of the biomedical field, self-healable hydrogels and

elastomers designed using (bio)degradable or bioeliminable polymer chains have been developed and are becoming increasingly popular. This review presents the latest advances in the field of self-healing degradable/bioeliminable networks designed for use in health applications. The strategies used to develop such networks based on reversible covalent or physical cross-linking or their combination via dual/multi-cross-linking approaches are analyzed in detail. The key parameters of these hydrogels and elastomers, such as mechanical properties, repair and degradation times, and healing efficiencies, are critically considered in terms of their suitabilities in biomedical applications. Finally, their current and prospective uses as biomaterials in the fields of tissue engineering, drug/cell delivery, and medical devices are presented, followed by the remaining challenges faced to ensure the further success of degradable self-healable networks.

ACS Appl. Mater. Interfaces 15, 2077-2091 (2023)

Mathilde Grosjean, Louis Gangolphe, Stéphane Dejean, Sylvie Hunger, Audrey Bethry, Frédéric Bossard, Xavier Garric, Benjamin Nottelet

ABSTRACT

In the biomedical field, degradable chemically crosslinked elastomers are interesting materials for tissue engineering applications since they present rubber-like mechanical properties matching with those of soft tissues and are able to preserve their 3D structure over degradation. Their use in biomedical applications requires surgical handling and implantation that can be source of accidental damages responsible for loss of properties. Therefore, their inability to be healed after damage or breaking can be a major drawback. In this work, biodegradable dual-crosslinked networks that exhibit fast and efficient self-healing properties at 37 °C are designed. Self-healable dual-crosslinked (chemically and physically) elastomeric networks are prepared from two methods. The first approach is based on the mix of hydrophobic PEG-PLA star-shaped copolymers functionalized either with catechol or methacrylate moieties. In the second approach, hydrophobic bifunctional PEG-PLA star-shaped copolymers with both catechol and methacrylate on their structure are used. In the two systems the supramolecular network is responsible for the self-healing properties thanks to the dynamic dissociation/re-association of the numerous hydrogen bonds between the catechol groups, whereas the covalent network ensures mechanical properties similar to pure methacrylate networks. The self-healable materials display mechanical properties that are compatible with soft tissues and exhibit linear degradation because of the chemical crosslinks. The performances of networks from mix copolymers vs. bifunctional copolymers are compared and demonstrate the superiority of the later. The biocompatibility of the materials is also demonstrated and confirm the potential of these degradable self-healable elastomeric networks to be used for the design of temporary medical devices.

Biomacromolecules 24,3472–3483 (2023)

Mathilde Grosjean, Dimitri Berne, Sylvain Caillol, Vincent Ladmiral, Benjamin Nottelet

ABSTRACT

The development of dynamic covalent chemistry opens the way to the design of materials able to be reprocessed by an internal exchange reaction under thermal stimulus. Imine exchange differs from other exchange reactions by its relatively low temperature of activation. In this study, amine-functionalized star-shaped PEG–PLA and an aldehyde-functionalized hydroxyurethane modifier were combined to produce PEG–PLA/hydroxyurethane networks incorporating imine bonds. The thermal and mechanical properties of these new materials were evaluated as a function of the initial ratio of amine/aldehyde used during synthesis. Rheological analyses highlighted the dynamic behavior of these vitrimers at moderate temperature (60–85 °C) and provided the flow activation energies. Additionally, the reprocessability of these PEG–PLA/hydroxyurethane vitrimers was assessed by comparing the material properties before reshaping and after three reprocessing cycles (1 ton, 1 h, 70 °C). Hence, these materials can easily be designed to satisfy a specific medical application without properties loss. This work opens the way to the development of a new generation of dynamic materials combining degradable PEG–PLA copolymers and hydroxyurethane modifiers, which could find applications in the shape of medical devices on-demand under mild conditions.

Adv. Funct. Mater 2205315 (2023)

Mathilde Grosjean, Louis Gangolphe, Benjamin Nottelet

ABSTRACT

Among biomaterials, 3D networks with capacities to absorb and retain large quantities of water (hydrogels) or withstand significant deformation and stress while recovering their initial structures at rest (elastomers) are largely used in biomedical applications. However, when damaged, they cannot recover their initial structures and properties. To overcome this limitation and satisfy the requirements of the biomedical field, self-healable hydrogels and

elastomers designed using (bio)degradable or bioeliminable polymer chains have been developed and are becoming increasingly popular. This review presents the latest advances in the field of self-healing degradable/bioeliminable networks designed for use in health applications. The strategies used to develop such networks based on reversible covalent or physical cross-linking or their combination via dual/multi-cross-linking approaches are analyzed in detail. The key parameters of these hydrogels and elastomers, such as mechanical properties, repair and degradation times, and healing efficiencies, are critically considered in terms of their suitabilities in biomedical applications. Finally, their current and prospective uses as biomaterials in the fields of tissue engineering, drug/cell delivery, and medical devices are presented, followed by the remaining challenges faced to ensure the further success of degradable self-healable networks.

Polymer Chemistry 11, 4438–4453 (2020)

Bláhová M., Randárová E., Konefał R., Nottelet B., Etrych T.

Biomacromolecules 19, 4003–4013 (2018)

Koziolova, E., Kostka, L., Kotrchova, L., Subr, V., Konefal, R., Nottelet, B. & Etrych, T.