Abstract:New
polymers are needed to address the shortcomings of commercially
available materials for soft tissue repair. Herein, we investigated
a series of l-valine-based poly(ester urea)s (PEUs) that
vary in monomer composition and the extent of branching as candidate
materials for soft tissue repair. The preimplantation Young’s
moduli (105 ± 30 to 269 ± 12 MPa) for all the PEUs are comparable
to those of polypropylene (165 ± 5 MPa) materials currently employed
in hernia-mesh repair. The 2% branched poly(1-VAL-8) … Show more
“…The granuloma was less than 200 μm thick for all samples, which has previously been reported as acceptable in terms of tissue compatibility for long-term implants 4 , 33 , 34 . This is indicative of the tunable degradation profiles from varied succinate content as increasing implant degradation rates correlates with greater cellular remodeling processes 34 . Fig.…”
Section: Introductionsupporting
confidence: 51%
“…This was noticeably greater than all other materials which elicited total scores ranging between 4.3 ± 1.2-4.9 ± 1.8, 3.8 ± 1.4 -4.7 ± 1.7, and 2.6 ± 1.3-4.0 ± 2.0 for 1, 2, and 4-months respectively. For reference, medical-grade polypropylene has scored around 7.5 in a similar recent study 34 . While used widely in the clinic, this value would be noted as a persistent low-level inflammatory response.…”
Complex biological tissues are highly viscoelastic and dynamic. Efforts to repair or replace cartilage, tendon, muscle, and vasculature using materials that facilitate repair and regeneration have been ongoing for decades. However, materials that possess the mechanical, chemical, and resorption characteristics necessary to recapitulate these tissues have been difficult to mimic using synthetic resorbable biomaterials. Herein, we report a series of resorbable elastomer-like materials that are compositionally identical and possess varying ratios of cis:trans double bonds in the backbone. These features afford concomitant control over the mechanical and surface eroding degradation properties of these materials. We show the materials can be functionalized post-polymerization with bioactive species and enhance cell adhesion. Furthermore, an in vivo rat model demonstrates that degradation and resorption are dependent on succinate stoichiometry in the elastomers and the results show limited inflammation highlighting their potential for use in soft tissue regeneration and drug delivery.
“…The granuloma was less than 200 μm thick for all samples, which has previously been reported as acceptable in terms of tissue compatibility for long-term implants 4 , 33 , 34 . This is indicative of the tunable degradation profiles from varied succinate content as increasing implant degradation rates correlates with greater cellular remodeling processes 34 . Fig.…”
Section: Introductionsupporting
confidence: 51%
“…This was noticeably greater than all other materials which elicited total scores ranging between 4.3 ± 1.2-4.9 ± 1.8, 3.8 ± 1.4 -4.7 ± 1.7, and 2.6 ± 1.3-4.0 ± 2.0 for 1, 2, and 4-months respectively. For reference, medical-grade polypropylene has scored around 7.5 in a similar recent study 34 . While used widely in the clinic, this value would be noted as a persistent low-level inflammatory response.…”
Complex biological tissues are highly viscoelastic and dynamic. Efforts to repair or replace cartilage, tendon, muscle, and vasculature using materials that facilitate repair and regeneration have been ongoing for decades. However, materials that possess the mechanical, chemical, and resorption characteristics necessary to recapitulate these tissues have been difficult to mimic using synthetic resorbable biomaterials. Herein, we report a series of resorbable elastomer-like materials that are compositionally identical and possess varying ratios of cis:trans double bonds in the backbone. These features afford concomitant control over the mechanical and surface eroding degradation properties of these materials. We show the materials can be functionalized post-polymerization with bioactive species and enhance cell adhesion. Furthermore, an in vivo rat model demonstrates that degradation and resorption are dependent on succinate stoichiometry in the elastomers and the results show limited inflammation highlighting their potential for use in soft tissue regeneration and drug delivery.
“…L-Valine-based poly(ester urea)s (PEUs) were synthesized using a two-step process, and the synthesis details were reported elsewhere. 59 In brief, an esterification was first performed between a L-valine and a diol (1,8-octanediol, 1,10-decanediol, and 1,12-dodecanediol) under acidic conditions (in the presence of p-toluenesulfonic acid (pTsOH) with toluene). Next, an interfacial polymerization of the respective monomers with triphosgene yielded the poly(ester urea) homopolymers (Scheme 1).…”
Section: ■ Experimental Sectionmentioning
confidence: 99%
“…The main body of the work presents a real-time mechano-optical study of a series of amorphous l -valine (VAL)-based PEUs to reveal the structural evolution during the uniaxial deformation. VAL-PEUs were chosen as they have demonstrated promising results as surgical meshes for soft tissue repairs, , where their shape memory properties will further provide the potential pathways for laparoscopic deployment and facilitate minimally invasive approaches for the implantation. In such applications, the ability for a device to precisely recover from the deformed state to the original shape is of vital importance .…”
The uniaxial mechano-optical behavior of a series of amorphous L-valine-based poly(ester urea) (VAL-PEU) with varying diol lengths was studied to elucidate the molecular mechanism associated with their thermal shape memory properties. A custom, real-time measurement system was used to capture the true stress, true strain, and birefringence during the temporary shape programming at stretching temperatures above the glass transition temperature (T g ). The mechanooptical response of VAL-PEUs exhibits an initial photoelastic behavior related to enhanced segmental correlation at low temperatures above the T g . A characteristic temperature, defined as the liquid−liquid (T ll ) transition (rubbery−viscous transition), was found at about 1.05 T g (K) (at T g + 15 °C) at strain rate of 0.017 s −1 , above which the segmental contacts largely "melt" and the initial slope of the stress-optical curves becomes temperature independent. This temperature corresponds to the temperature where mean relaxation time for the polymer is maximized. Real-time infrared spectroscopy (IR) and in situ wideangle X-ray scattering (WAXS) revealed a strain-induced intersegmental structural change during stretching. The intermolecular hydrogen bonding between the urea−urea and/or urea−carbonyl groups was found to adopt different bonding modes at the onset of strain hardening with a concurrent increased separation distance between adjacent segments. The hydrogen bonding strengthened supramolecular packing. The compromised shape recovery is a result of the disruption of the rigid segmental correlation, induced either by large extension at T < T ll or by progressive thermal effects at T > T ll , both of which may be minimized at T ll .
“…The polypeptides were explored for biomedical applications in drug and gene delivery, tissue engineering, reinforced nanocomposites in bone replacement, and so on. − In the last two decades, polycondensation approaches have been developed to construct nonpeptide polymer analogues from l -amino acid resources for biomedical application . Some of the most important nonpeptide polymers are poly(ester–amide)s, − polycarbonates, − poly(ester-urethane-urea), − poly(ester-urea), − poly(disulfide-urethane)s, − and poly(acetal-urethane), among others. We have reported a melt polycondensation route to make linear poly(ester-urethane)s − hyperbranched poly(ester-urethane)s, amine and disulfide-functionalized polyesters, , pH and enzyme-responsive aliphatic polyesters and thermoresponsive poly(ester-urethane)s and polyurethanes, and so on.…”
Hydroxyl-functionalized amphiphilic polyesters based on L-amino acid bioresources were designed and developed, and their nanoassemblies were explored as intracellular enzyme-biodegradable scaffolds for delivering anticancer drugs and fluorophores to cancer cells. To accomplish this task, acetal-masked multifunctional dicarboxylic ester monomer from L-aspartic acid was tailor-made, and it was subjected to solvent-free melt transesterification polycondensation with commercial diols to produce acetal-functionalized polyesters. Acidcatalyzed postpolymerization deprotection of these acetal-polyesters produced amphiphilic hydroxyl-functionalized polyesters. The amphiphilic polyesters were self-assembled in aqueous medium to produce nanoparticles of size <200 nm. Wide ranges of both water-soluble and water-insoluble anticancer drugs such as doxorubicin (DOX), camptothecin (CPT), and curcumin (CUR) and fluorophores such as Nile red (NR), Rose Bengal (RB), and Congo red (CR) were encapsulated in hydroxyl polyesters nanoparticles. In vitro drug release studies revealed that the aliphatic polyester backbone underwent lysosomal enzymatic-biodegradation to release the loaded cargoes at the intracellular compartments. Lysotracker-assisted live-cell confocal microscopy studies further confirmed the colocalization of the polymer nanoscaffolds in the lysosomes and supported their enzymatic-biodegradation for drug delivery. In vitro cytotoxicity studies showed that the nascent polymers were not toxic, whereas their anticancer drug-loaded nanoparticles exhibited excellent cell killing in cervical cancer (HeLa) cell lines. The drug-loaded (CPT, CUR, and DOX) and the fluorophore-loaded (NR, RB, and CR) polymer nanoparticles were highly luminescent; thus, the encapsulated polymer nanoparticles enabled the multiple color-tunable bioimaging in cancer cells in the entire visible region from blue to deep red. Time-dependent live-cell confocal microscopy studies established that the cellular uptake of drugs and fluorophores was 5 to 10-fold higher while they were delivered from the hydroxyl polyester platform. The hydroxyl polyester nanocarrier design strategy opens up new opportunities in drug delivery to cancer cells from a biodegradable polymer platform based on L-amino acids.
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