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Digital light processing (DLP) 3D printing has shown great advantages such as high resolution in the fabrication of 3D objects toward a range of applications. Despite the rapid development of photocurable materials for DLP printing, tailoring properties to meet the specific demands for various applications remains challenging. Herein, we introduce copolymers of caprolactone and allyl caprolactone offering built-in functionality for thiol-ene photochemistry, thereby omitting the need for postfunctionalization. A crystalline block copolymer and an amorphous statistical copolymer were synthesized with the same comonomer composition and molecular weight. Thio-ene photocuring with a tetrafunctional thiol cross-linker was studied at different thiol to double-bond ratios for the copolymers and their blends. All formulations undergo rapid photocuring within several seconds of irradiation with slightly higher gel fractions observed for the statistical copolymer over the block copolymer under the same conditions, suggesting a somewhat higher cross-link density. Thermal properties of the networks were dependent on the presence of the semicrystalline block copolymer, where higher melting enthalpies were reached at higher block copolymer content. Similarly, crystallinity was found to be the main contributor to the mechanical properties. For a comparable composition, the modulus of a block copolymer network was found to be 31 times higher than that of the statistical copolymer network (27.7 vs 0.89 MPa). Intermediate moduli could be obtained by blending the two copolymers. DLP-printed scaffolds from these copolymers retained their thermal properties, therefore offering an efficient approach to tailoring mechanical properties, through crystallinity. Moreover, the printed scaffold displayed shape memory properties as the first example of poly(carprolactone) (PCL) copolymers in DLP printing. These materials are readily synthesized, offer fast and high-resolution 3D printing, and are degradable and cell compatible. They offer a straightforward approach to tailoring properties of PCL-based biomaterials and devices., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Poly(proline) II helical motifs located at the protein-water interface stabilize the three-dimensional structures of natural proteins. Reported here is the first example of synthetic biomimetic poly(proline)-stabilized polypeptide nanostructures obtained by a straightforward ring-opening polymerization-induced self-assembly (ROPISA) process through consecutive N -carboxyanhydride (NCA) polymerization. It was found that the use of multifunctional 8-arm initiators is critical for the formation of nanoparticles. Worm-like micelles as well as spherical morphologies were obtained as confirmed by dynamic light scattering (DLS), transmission electron microscopy (TEM), and small angle X-ray scattering (SAXS). The loading of the nanostructures with dyes is demonstrated. This fast and open-vessel procedure gives access to amino acids-based nanomaterials with potential for applications in nanomedicine.

Homopolymerization of ortho-nitrobenzyl ( o NB)-protected l-cysteine and l-glutamic acid was systematically studied in different solvents and at different monomer to initiator ratios, revealing the best reaction control in dimethylformamide (DMF) across a range of degrees of polymerization. In the subsequent ultraviolet (UV)-cleavage studies, it was found that quantitative deprotection upon UV exposure at 365 nm was not achievable for either of the homopolypeptides as confirmed by 1 H NMR and UV/visible (UV/vis) analyses. While the poly( o NB-l-cysteine) deprotected more readily with no effect of the polypeptide molecular weight, lower molecular weight poly( o NB-l-glutamate) reached maximum deprotection faster than high molecular weight samples. This was further confirmed by the pH changes of the solution. When incorporated into the core of miniemulsion-derived nanoparticles, both o NB-protected copolypeptides were successfully deprotected as evident from a color change and a pH change in the case of poly( o NB-l-glutamate). However, the removal of the deprotection byproduct nitrosobenzaldehyde proved unsuccessful, which indicates a diffusion barrier caused by the nanoparticle's surfactant. The study provides insights and guidelines for the UV deprotection of polypeptides and demonstrates the ability to selectively UV-deprotect polypeptides in the confined space of a nanoparticle dispersion., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Ice-binding proteins (IBPs) from extremophile organisms can modulate ice formation and growth. There are many (bio)technological applications of IBPs, from cryopreservation to mitigating freeze-thaw damage in concrete to frozen food texture modifiers. Extraction or expression of IBPs can be challenging to scale up, and hence polymeric biomimetics have emerged. It is, however, desirable to use biosourced monomers and heteroatom-containing backbones in polymers for in vivo or environmental applications to allow degradation. Here we investigate high molecular weight polyproline as an ice recrystallization inhibitor (IRI). Low molecular weight polyproline is known to be a weak IRI. Its activity is hypothesized to be due to the unique PPI helix it adopts, but it has not been thoroughly investigated. Here an open-to-air aqueous N -carboxyanhydride polymerization is employed to obtain polyproline with molecular weights of up to 50000 g mol -1 . These polymers were found to have IRI activity down to 5 mg mL -1 , unlike a control peptide of polysarcosine, which did not inhibit all ice growth at up to 40 mg mL -1 . The polyprolines exhibited lower critical solution temperature behavior and assembly/aggregation observed at room temperature, which may contribute to its activity. Single ice crystal assays with polyproline led to faceting, consistent with specific ice-face binding. This work shows that non-vinyl-based polymers can be designed to inhibit ice recrystallization and may offer a more sustainable or environmentally acceptable, while synthetically scalable, route to large-scale applications.

Statistical copolypeptides comprising lysine and tyrosine with unprecedented ion-induced gelation behavior are reported. Copolypeptides are obtained by one-step N -carboxyanhydride (NCA) ring-opening polymerization. The gelation mechanism is studied by in situ SAXS analyses, in addition to optical spectroscopy and transmission electron microscopy (TEM). It is found that the gelation of these statistically polymerized polypeptides is due to the formation of stable intermolecular β-sheet secondary structures induced by the presence of salt ions as well as the aggregation of an α-helix between the copolypeptides. This behavior is unique to the statistical lysine/tyrosine copolypeptides and was not observed in any other amino acid combination or arrangement. Furthermore, the diffusion and mechanical properties of these hydrogels can be tuned through tailoring the polypeptide chain length and ion strength.

We report the synthesis and photophysical properties of a neutral BODIPY photosensitizing copolymer (poly-8-(4-hydroxymethylphenyl)-4,4-difluoro-2,6-diethynyl-4-bora-3a,4a-diaza- s -indacene) containing ethynylbenzene links between the BODIPY units. The copolymer absorbs further towards the red in the UV-vis spectrum compared to the BODIPY precursor. Photolysis of the polymer produces a singlet excited state which crosses to the triplet surface in less than 300 ps. This triplet state was used to form singlet oxygen with a quantum yield of 0.34. The steps leading to population of the triplet state were studied using time-resolved spectroscopic techniques spanning the pico- to nanosecond timescales. The ability of the BODIPY polymer to generate a biocidal species for bactericidal activity in both solution- and coating-based studies was assessed. When the BODIPY copolymer was dropcast onto a surface, 4 log and 6 log reductions in colony forming units/ml representative of Gram-positive and Gram-negative bacteria, respectively, under illumination at 525 nm were observed. The potent broad-spectrum antimicrobial activity of a neutral metal-free copolymer when exposed to visible light conditions may have potential clinical applications in infection management.

Mucosal delivery across the gastrointestinal (GI) tract, airways, and buccal epithelia is an attractive mode of therapeutic administration, but the challenge is to overcome the mucus and epithelial barriers. Here, we present degradable star polypept(o)ides capable of permeating both barriers as a promising biomaterial platform for mucosal delivery. Star polypept(o)ides were obtained by the initiation of benzyl-l-glutamate N -carboxyanhydride (NCA) from an 8-arm poly(propyleneimine) (PPI) dendrimer, with subsequent chain extension with sarcosine NCA. The hydrophobic poly(benzyl-l-glutamate) (PBLG) block length was maintained at 20 monomers, while the length of the hydrophilic poly(sarcosine) (PSar) block ranged from 20-640 monomers to produce star polypept(o)ides with increasing hydrophilic: hydrophobic ratios. Transmission electron microscopy (TEM) images revealed elongated particles of ∼120 nm length, while dynamic light scattering (DLS) provided evidence of a decrease in the size of polymer aggregates in water with increasing poly(sarcosine) block length, with the smallest size obtained for the star PBLG 20 - b -PSar 640 . Fluorescein isothiocyanate (FITC)-conjugated PBLG 20 - b -PSar 640 permeated artificial mucus and isolated rat mucus, as well as rat intestinal jejunal tissue mounted in Franz diffusion chambers. An apparent permeability coefficient ( P app ) of 15.4 ± 3.1 ×10 -6 cm/s for FITC-PBLG 20 - b -PSar 640 was calculated from the transepithelial flux obtained with the apical-side addition of 7.5 mg polypept(o)ide to jejunal tissue over 2 h. This P app could not be accounted for by flux of unconjugated FITC. Resistance to trypsin demonstrated the stability of FITC-labeled polypept(o)ide over 2 h, but enzymatic degradation at the mucus-epithelial interface or during flux could not be ruled out as contributing to the P app . The absence of any histological damage to the jejunal tissue during the 2 h exposure suggests that the flux was not associated with overt toxicity.

Disinfection/sterilization is an essential step during the manufacturing process of any implantable medical device. Cross-linking is also required for biopolymers to control resistance to degradation and enhance mechanical integrity. To date, there is still no single disinfection/sterilization treatment and cross-linking method that can be used universally for collagen-based devices. Herein, we assessed the influence of ethylene oxide, ethanol, gamma irradiation, and gas plasma disinfection/sterilization on the structural, biophysical, biochemical, and biological properties of self-assembled collagen films cross-linked with 4-arms polyethylene glycol succinimidyl glutarate and genipin. Microscopy analysis revealed that gas plasma treatment induced the most profound differences in the non-cross-linked and 4-arms polyethylene glycol succinimidyl glutarate cross-linked collagen films. Gas plasma also significantly increased the swelling ratio of the non-cross-linked and the 4-arms polyethylene glycol succinimidyl glutarate cross-linked films. Non-cross-linked and gas plasma treated 4-arms polyethylene glycol succinimidyl glutarate collagen films exhibited the lowest resistance to collagenase degradation and denaturation temperature. Between the non-cross-linked groups, the gas plasma treatment resulted in the collagen films with the lowest stress at break, strain at break, force at break, and Young's modulus values. Within the 4-arms polyethylene glycol succinimidyl glutarate groups, the ethylene oxide treatment resulted in collagen films with the lowest stress at break, strain at break, force at break, and Young's modulus values. Within the genipin groups, the gas plasma treatment resulted in collagen films with the lowest stress at break, strain at break, force at break, and Young's modulus values. Proliferation, metabolic activity, and viability of human skin fibroblasts were not affected as a function of cross-linking method and disinfection/sterilization treatment. However, proliferation, metabolic activity, and viability of THP1 cells were significantly reduced as a function of the cross-linking method, but they were not affected as a function of the disinfection/sterilization treatment. Overall, our data illustrate that the cross-linking method and the disinfection/sterilization treatment differentially affect the structural, biophysical, biochemical, and biological properties of collagen-based devices, and thus, they should be optimized according to the clinical indication.

Biomimetic tissue engineering aspires to develop bioinspired implantable devices that would positively interact with the host. Given that glycosaminoglycans are involved in many physiological processes, whereas their deprivation is associated with pathophysiologies, functionalization of implantable devices with natural and/or synthetic carbohydrate moieties is at the forefront of scientific research and industrial innovation. Herein, we venture to assess the influence of various concentrations (0.01%, 0.1%, 1%) of hyaluronic acid and Ficoll on the structural, thermal, biomechanical and biological (human osteoblasts) properties of electrospun poly(lactic- co -glycolic acid) fibers. The addition of hyaluronic acid and Ficoll reduced the fiber diameter, with the 1% hyaluronic acid exhibiting the smallest fibers diameter ( p < 0.001). Neither the addition of hyaluronic acid nor the addition Ficoll significantly affected the onset and peak temperatures ( p > 0.05). All hyaluronic acid and Ficoll treatments significantly reduced stress at break, strain at break and elastic modulus values ( p < 0.001). Hyaluronic acid and Ficoll did not affect osteoblast viability and metabolic activity temperatures ( p > 0.05); the 1% hyaluronic acid and Ficoll significantly increased ( p < 0.001) osteoblast proliferation at day 21. By day 21, the 1% hyaluronic acid and 1% Ficoll fibers showed the highest alkaline phosphatase activity and calcium deposition. At day 21, osteocalcin was not detected, whereas osteopontin was detected on all samples. Collectively, our data clearly illustrate the biological benefit of nonsulfated polysaccharides as functionalization molecules.