Unique Biodegradation Research Articles

Biodegradation of various edible oils and fat by Staphylococcus petrasii sub sp. jettensis VSJK R1 for application in bioremediation of lipid rich restaurant wastewater.

The disposal of fat, oil, and grease (FOG) pollutants from various sources, including restaurants, food processing facilities, and domestic kitchens, poses significant challenges to wastewater treatment systems. In this study, we isolated and characterized a novel bacterial strain. The result of 16S rRNA gene and phylogenetic analysis showed that the isolate was Staphylococcus petrasii sub sp. jettensis and named as VSJK R1 (Fig. S1). It was tested for its biodegradation potential of FOG contaminants. Our investigation revealed that Staphylococcus petrasii sub sp. jettensis VSJK R1 effectively degraded a variety of edible oils, including soybean, sunflower, cottonseed, palm, groundnut, and butter, with notable efficiency. Optimization studies were conducted to determine the optimal conditions for biodegradation, including the effects of nitrogen, carbon, phosphorus, pH, temperature, and salt concentration. Results indicated that organic nitrogen sources and glucose as carbon source significantly enhanced biodegradation rates, while the addition of phosphorus further improved degradation efficiency within specific concentration ranges. Moreover, the optimal pH for biodegradation was found to be neutral, with temperature ranging between 22°C and 45°C favoring microbial activity. Remarkably, Staphylococcus petrasii sub sp. jettensis VSJK R1 exhibited resilience to high salt concentrations, making it suitable for treatment of wastewater with elevated salt content. Additionally, comparative studies with other microbial strains underscored the unique biodegradation capabilities of Staphylococcus petrasii sub sp. jettensis VSJK R1, particularly in degrading various edible oils. The results suggest promising applications of this novel isolate in bioremediation efforts targeting FOG pollutants in wastewater treatment plants and grease traps. Future research may focus on scaling up the bioremediation process and field testing the efficacy of Staphylococcus petrasii sub sp. jettensis VSJK R1 in real-world wastewater treatment scenarios.

Exploratory Investigation of Zinc-Modified Borosilicate Bioactive Glass: A New Methodology for Its Biocompatibility, Immunoregulation, and Pro-Angiogenic Property Evaluation.

The assessment of biodegradable materials, such as bioactive glass, under the existing ISO 10993 standard test methods poses a significant challenge due to potential cell viability impairment caused by the accumulation of degraded products in a static environment. Therefore, innovative methodologies are urgently needed to tailor the unique biodegradation characteristics of these materials, providing more precise and scientific insights into biosafety and efficacy verification. Motivation by its bidirectional regulation of angiogenesis and immunity, zinc (Zn) was incorporated into sol-gel-derived borosilicate bioactive glasses (SBSGs) to fabricate Zn-incorporated borosilicate bioactive glasses (SBSG-Zn) to complement the tissue repair capabilities of bioactive glasses. Both SBSG and SBSG-Zn glasses consist of nanosized particles, slit mesoporous pores, high specific surface areas, and bioreactivity. In vitro comparative analysis, conducted according to ISO 10993 standards, demonstrates that only at suitable dilution rates─such as the 8-fold dilution employed in this study─do extracts of SBSG and SBSG-Zn glasses exhibit low cytotoxicity when cultured with human umbilical vein endothelial cells (HUVECs). Notably, SBSG-Zn glasses show optimal promotion of angiogenic gene expression in HUVECs. Furthermore, within an appropriate concentration range of released ions, SBSG-Zn glass extracts not only promote cell survival but also modulate the expression of anti-inflammatory genes while simultaneously inhibiting pro-inflammatory genes concurrently. After being implanted in rat subcutaneous defect models, both SBSG and SBSG-Zn glasses demonstrated the local immunoregulation and angiogenic effects. SBSG-Zn stands out by demonstrating superior modulation of M1/M2 polarization in macrophages as validated by altered secretion of key factors in macrophages and expression of relevant growth factors in HUVECs. These findings underscore the potential for convenient manipulation of localized angiogenic and immunoregulation through the incorporation of zinc into bioactive glass, emphasizing the importance of ensuring the appropriate ion doses are applied for achieving optimal therapeutic efficiency.

The unique biodegradation pathway of benzo[a]pyrene in moderately halophilic Pontibacillus chungwhensis HN14

Benzo[a]pyrene (BaP), as the typical representative of polycyclic aromatic hydrocarbons (PAHs), is a serious hazard to human health and natural environments. Though the study of microbial degradation of PAHs has persisted for decades, the degradation pathway of BaP is still unclear. Previously, Pontibacillus chungwhensis HN14 was isolated from high salinity environment exhibiting a high BaP degradation ability. Here, based on the intermediates identified, BaP was found to be transformed to 4,5-epoxide-BaP, BaP-trans-4,5-dihydrodiol, 1,2-dihydroxy-phenanthrene, 2-carboxy-1-naphthol, and 4,5-dimethoxybenzo[a]pyrene by the strain HN14. Furthermore, functional genes involved in degradation of BaP were identified using genome and transcriptome data. Heterogeneous co-expression of monooxygenase CYP102(HN14) and epoxide hydrolase EH(HN14) suggested that CYP102(HN14) could transform BaP to 4,5-epoxide-BaP, which was further transformed to BaP-trans-4,5-dihydrodiol by EH(HN14). Moreover, gene cyp102(HN14) knockout was performed using CRISPR/Cas9 gene-editing system which confirmed that CYP102(HN14) play a key role in the initial conversion of BaP. Finally, a novel BaP degradation pathway was constructed in bacteria, which showed BaP could be converted into chrysene, phenanthrene, naphthalene pathways for the first time. These findings enhanced our understanding of microbial degradation process for BaP and suggested the potential of using P. chungwhensis HN14 for bioremediation in PAH-contaminated environments.

Photopolymerization Inks for 3D Printing of Elastic, Strong, and Biodegradable Oral Delivery Devices

AbstractThree‐dimensional (3D) printing via vat photopolymerization is transforming the manufacturing paradigms of biomedical devices, offering tremendous advantages for the production of customized advanced drug delivery systems. However, the existing commercial inks often lack the ability to simultaneously provide elasticity, strength, and biodegradability. Herein, photopolymerizable inks based on poly(β‐aminoester) diacrylates and N‐vinyl pyrrolidone are used to address these limitations. These biodegradable polymers enable the digital light processing 3D printing of elastomers with adjustable elongation at break (103–762%), stress at failure (0.2–8.3 MPa), and hydrolysis rates ranging from 25 min to 80 days. The authors are able to synthesize a soft polymer that possess properties akin to natural latex, which can enhance its elastic modulus when subjected to high strains. It can withstand 762% stretch with a maximum strength of 8.3 MPa. In addition, this polymer demonstrates cytocompatibility and unique biodegradation properties under simulated gastrointestinal conditions (within hours at pH 6.8). By utilizing this elastomer, a prototype of an expandable oral drug delivery device that has the ability to degrade within the average transit time in the jejunum is manufactured. This study paves the way to leverage vat photopolymerization 3D printing in the creation of complex prototypes of biomedical devices where strength, elasticity and biodegradability are essential.

Electrospun methacrylated natural/synthetic composite membranes for gingival tissue engineering

New functional materials for engineering gingival tissue are still in the early stages of development. Materials for such applications must maintain volume and have advantageous mechanical and biological characteristics for tissue regeneration, to be an alternative to autografts, which are the current benchmark of care. In this work, methacrylated gelatin (GelMa) was photocrosslinked with synthetic immunomodulatory methacrylated divinyl urethanes and defined monomers to generate composite scaffolds. Using a factorial design, with the synthetic monomers of a degradable polar/hydrophobic/ionic polyurethane (D-PHI) and GelMa, composite materials were electrospun with polycarbonate urethane (PCNU) and light-cured in-flight. The materials had significantly different relative hydrophilicities, with unique biodegradation profiles associated with specific formulations, thereby providing good guidance to achieving desired mechanical characteristics and scaffold resorption for gingival tissue regeneration. In accelerated esterase/collagenase degradation models, the new materials exhibited an initial rapid weight loss followed by a more gradual rate of degradation. The degradation profile allowed for the early infiltration of human adipose-derived stromal/stem cells, while still enabling the graft's structural integrity to be maintained. In conclusion, the materials provide a promising candidate platform for the regeneration of oral soft tissues, addressing the requirement of viable tissue infiltration while maintaining volume and mechanical integrity. Statement of significanceThere is a need for the development of more functional and efficacious materials for the treatment of gingival recession. To address significant limitations in current material formulations, we sought to investigate the development of methacrylated gelatin (GelMa) and oligo-urethane/methacrylate monomer composite materials. A factorial design was used to electrospin four new formulations containing four to five monomers. Synthetic immunomodulatory monomers were crosslinked with GelMa and electrospun with a polycarbonate urethane resulting in unique mechanical properties, and resorption rates which align with the original design criteria for gingival tissue engineering. The materials may have applications in tissue engineering and can be readily manufactured. The findings of this work may help better direct the efforts of tissue engineering and material manufacturing.

From nanoscale to microscale hierarchical multifunctional nano borate bioactive glass for efficient wound healing

The unique biodegradation and mineralization properties of nanosized CO32−- containing hydroxyapatite (HCA)-coated BBG (nano-HCA@BG) make it a promising material for soft tissue repair. However, its single-function solid powder form makes it difficult to control drug release rates, limiting its potential in vivo application. To address this challenge, we designed a hierarchical multifunctional composite by incorporating gelatin with nano-HCA@BG loaded with AgNPs. The hierarchical composite achieved a high degree of structural fit from nanometer to micrometer scale, as demonstrated by structural characterization results. The composite showed improved encapsulation of nanodrug and controlled degradation, as confirmed by degradation and antimicrobial property results. Wound healing experiments in vivo revealed efficient encapsulation of nano-HCA@BG through specific combination of gelatin and nano-HCA@BG, leading to improved controlled degradation and biological activity of the glass. The study also developed a dynamic flowing drug loading method that integrated material preparation and drug loading, thus improving the efficiency of drug loading of the nano-HCA@BG. Overall, our study demonstrates a new method for the preparation of hierarchical functional biomaterials of bioglass, laying the foundation for nano-HCA@BG to play an important role in tissue repair. Moreover, our findings suggest that better understanding of the structure and biological properties of nano-HCA@BG could expand its application in other biomedical fields such as drug delivery.

Fabrication of magnesium oxide nanoparticles using Eucalyptus tereticornis seed extract and their characterisation

Abstract The green approach is a simple and efficient method for generating metal oxide nanoparticles. Magnesium oxide nanoparticles gained prominence due to their unique biodegradation, microbe growth inhibition, and non-toxicity properties. The seed extract of Eucalyptus tereticornis was used to make magnesium oxide nanoparticles in this research. Using X-ray diffraction data, the average crystallite size of nanoparticles is estimated to be about 10 nm. Face-centered cubic structured magnesium oxide nanoparticles have a spherical surface morphology, as seen in transmission electron microscopy and scanning electron microscopy images. Fourier transform infra-red spectra are used to identify functional groups involved in the stabilization and reduction of precursor salt. Magnesium oxide nanoparticles are employed for a variety of applications including temperature dehydrating agents, high-grade ceramic materials, optoelectronic fields, and bio-medical studies such as antibacterial and antimicrobial.

The influence of yttrium and manganese additions on the degradation and biocompatibility of magnesium-zinc-based alloys: In vitro and in vivo studies

The repair and regeneration of bone defects are highly challenging orthopedic problems. Recently, Mg-based implants have gained popularity due to their unique biodegradation and elastic modulus similar to that of human bone. The aim of our study is to develop a magnesium alloy with a controllable degradation that can closely match bone tissue to help injuries heal in vivo and avoid cytotoxicity caused by a sudden increase in ion concentration. In this study, we prepared and modified Mg-3 Zn, Mg-3Zn-1Y, and Mg-2Zn-1Mn by hot extrusion, and used Mg-2.5Y-2.5Nd was as a control. We then investigated the effect of additions of Y and Mn on alloys’ properties. Our results show that Mn and Y can improve not only compression strength but also corrosion resistance. The alloy Mg-2Zn-1Mn demonstrated good cytocompatibility in vitro, and for this reason we selected it for implantation in vivo. The degraded Mg-2Zn-1Mn implanted a bone defect area did not cause obvious rejection and inflammatory reaction, and the degradation products left no signs of damage to the heart, liver, kidney, or brain. Furthermore, we find that Mg-2Zn-1Mn can promote an osteoinductive response in vivo and the formation of bone regeneration.

Tumor-Selective Biodegradation-Regulated Photothermal H2 S Donor for Redox Dyshomeostasis- and Glycolysis Disorder-Enhanced Theranostics.

H2 S-mediated tumor therapy has received great attention due to its unique physiological activity and synergistical enhancement, but suffers from limited H2 S donors with promised biosafety to regulate the H2 S delivery and subsequently the elusive pathway to augment the combined therapy. Herein, a PEGylated porous molybdenum disulfide nanoflower (MSP) with abundant defects is facilely synthesized for tumor-targeted theranostics. MSP possesses good water-dispersity and high photothermal ability, which is used for photoacoustic imaging and photothermal therapy. Interestingly, MSP is selectively degraded upon exposure to superfluous glutathione (GSH) within tumor cells, the mechanism of which is investigated, as a reduction-coordination reaction. This special degradation induces redox dyshomeostasis via GSH depletion for reactive oxygen species-accumulated chemodynamic therapy. Meanwhile, the selective biodegradation of MSP regulates a sustained H2 S release within tumor and achieves a targeted H2 S gas therapy via enhancing the glycolysis to acidify the tumor cells (glycolysis disorder). Synergistically, these performances are further enhanced via near-infrared photothermal heating, where excellent therapeutic outcomes with good biosafety are accomplished in vitro and in vivo. These characteristics, together with the unique biodegradation and no obvious side-effects of the nanoparticles, suggest a potential therapeutic strategy for precise tumor treatments.

Bacterial inactivation characteristics of magnesium–calcium–zinc alloys for bone implants

The understanding of adhesion and survival behavior of bacterial pathogens on implant surfaces are critical to control and reduce implant-associated infections. Herein, the authors investigate the interactions of Staphylococcus aureus, one of the most prevalent causes of implant infections, with Mg–4Zn–0.5Ca implants. It was found that within 60 min of exposure, 99.1% of adherent bacteria were inactivated. The combination of unique mechanical properties, biodegradation kinetics, and antimicrobial characteristics of Mg–4Zn–0.5Ca alloy makes it a promising candidate for future implant applications.

Actinomycetes Rhodococcus ruber CGMCC 17550 degrades neonicotinoid insecticide nitenpyram via a novel hydroxylation pathway and remediates nitenpyram in surface water

Neonicotinoid insecticides are neurotoxicants that cause serious environmental pollution and ecosystem risks. In the present study, a nitenpyram-degrading bacterium, Rhodococcus ruber CGMCC 17550, was isolated from a nitenpyram production sewage treatment tank. Liquid chromatography-mass spectrometry analysis revealed R. ruber degraded nitenpyram via a novel hydroxylation pathway to form three different metabolites, one of which was confirmed to hydroxylate nitenpyram at the C3 site of the 6-chlorpyridine cycle by nuclear magnetic resonance analysis. The nitenpyram degradation rate increased as the biomass of resting R. ruber CGMCC 17550 cells increased, reaching 98.37% at an OD600 of 9 in transformation broth containing 100 mg L−1 nitenpyram after 72 h of incubation. Nitenpyram degradation by R. ruber CGMCC 17550 was insensitive to dissolved oxygen levels. Use of glucose, fructose and pyruvate as co-substrates slightly increased nitenpyram degradation. The cytochrome P450 inhibitor 1-aminobenzotriazole strongly inhibited nitenpyram degradation, indicating that P450 enzymes may mediate nitenpyram hydroxylation. Inoculation of R. ruber CGMCC 17550 enhanced nitenpyram degradation in surface water. Additionally, R. ruber cells immobilized by calcium-alginate remediated 87.11% of 100 mg L−1 NIT in 8 d. Genome sequencing analysis confirmed that R. ruber CGMCC 17550 has metabolic diversity and abundant KEGG genes involved in xenobiotics biodegradation and metabolism. These findings demonstrate that R. ruber CGMCC 17550 is capable of unique biodegradation of nitenpyram via the hydroxylation pathway and is a promising bacterium for bioremediation of contaminants.

Draft genome of Meyerozyma guilliermondii strain vka1: a yeast strain with composting potential

BackgroundMeyerozyma guilliermondii is a yeast which could be isolated from a variety of environments. The vka1 strain isolated and purified from the organic compost was found to have composting potential. To better understand the genes assisting the composting potential in this yeast, whole genome sequencing and sequence annotation were performed. ResultsThe genome of M. guilliermondii vka1 strain was sequenced using a hybrid approach, on Illumina Hiseq-2500 platform at 100× coverage followed by Nanopore platform at 20× coverage. The de novo assembly using dual-fold approach had given draft genome of 10.8 Mb size. The genome was found to contain 5385 genes. The annotation of the genes was performed, and the enzymes identified to have roles in the degradation of macromolecules are discussed in relation to its composting potential. Annotation of the genome assembly of the related strains had revealed the unique biodegradation related genes in this strain. Phylogenetic analysis using the rDNA region has confirmed the position of this strain in the Ascomycota family. Raw reads are made public, and the genome wide proteome profile is presented to facilitate further studies on this organism. ConclusionsMeyerozyma guilliermondii vka1 strain was sequenced through hybrid approach and the reads were de novo assembled. Draft genome size and the number of genes in the strain were assessed and discussed in relation to the related strains. Scientific insights into the composting potential of this strain are also presented in relation to the unique genes identified in this strain.

Fibrin – a promising material for vascular tissue engineering

This review looks at the use of fibrin in vascular tissue engineering (VTE). Autologous fibrin is one of the most affordable biopolymers because it can be obtained from peripheral blood by simple techniques. A description and comparative analysis of the methods and approaches for producing fibrin gel is provided. The ability of fibrin to promote cell attachment and migration, survival and angiogenesis, to accumulate growth factors and release them in a controlled manner, are unique and extremely useful in VTE. Fibrin gels can serve as a three-dimensional matrix molded in different sizes and shapes to be applied in a variety of ways, including as a scaffold, coating, or impregnation material. Fibrin’s high porosity and biodegradability allows controllable release of growth factors, yet fibrinolysis must be tightly regulated to avoid side effects. We discuss the main methods of regulating the rate of fibrinolysis, as well as possible side effects of such exposure. Low mechanical strength is the main limitation in using fibrin as a scaffold for vascular tissue engineering. Possible options for increasing the strength properties of fibrin matrix and evaluating their effectiveness are presented. We propose that unique biocompatibility and ideal biodegradation profile of fibrin justify its use as a scaffold material for developing an ideal fully autologous small-diameter tissue-engineered vascular graft.

Biodegradable and photostable Nb2C MXene quantum dots as promising nanofluorophores for metal ions sensing and fluorescence imaging

Conventional fluorescent probes are either easily photobleached or non-biodegradable, which often leads to the unstable fluorescence signal output and long-term biological toxicity. Therefore, the development of novel fluorescent materials with both excellent photostability and biodegradability is of great significance for further broadening their application in numerous research fields. In this work, Nb2C quantum dots (Nb2C QDs) with pristine crystallographic structures of Nb2C MXene phases and surface oxygen-containing species are synthesized by an ultrasound assisted physicochemical exfoliation in tetrapropylammonium hydroxide. Detailed analyses indicate that the Nb2C QDs not only possess excellent chemical- and photo-stable fluorescence emission but also achieve successful application in fluorescence sensing of heavy metal ions and fluorescence imaging. More importantly, it is confirmed that the Nb2C QDs present high biocompatibility and unique biodegradation property responsive to human myeloperoxidase, implying the application safety of Nb2C QDs in vivo. Under the background of ever-growing and stringent requirements for biosafety and technical stability, the chemical- and photo-stability, biocompatibility, biodegradability, and most importantly the promising fluorescence sensing/imaging characteristic of the obtained Nb2C QDs may argue well for their future applications in environmental monitoring, biomedical diagnosis, visual display, and anti-counterfeiting.

Preparation and applications of peptide-based injectable hydrogels.

In situ injectable hydrogels have shown tremendous potential application in the biomedical field due to their significant drug accumulation at lesion sites, sustained release and markedly reduced systemic side effects. Specifically, peptide-based hydrogels, with unique biodegradation, biocompatibility, and bioactivity, are attractive molecular skeletons. In addition, peptides play a prominent role in normal metabolism, mimicking the natural tissue microenvironment and responding to stimuli in the lesion environment. Their advantages endow peptide-based hydrogels with great potential for application as biomedical materials. In this review, the fabrication and production of peptide-based hydrogels are presented. Several promising candidates, which are smart and environment-sensitive, are briefly reviewed. Then, the recent developments of these hydrogels for biomedical applications in tissue engineering, as drug/gene vehicles, and anti-bacterial agents are discussed. Finally, the development of peptide-based injectable hydrogels for biomedical applications in the future is surveyed.

Additively manufactured biodegradable porous magnesium.

The ideal biomaterials for bone tissue regeneration should be bone-mimicking in terms of mechanical properties, present a fully interconnected porous structure, and exhibit a specific biodegradation behavior to enable full regeneration of bony defects. Recent advances in additive manufacturing have resulted in biomaterials that satisfy the first two requirements but simultaneously satisfying the third requirement has proven challenging so far. Here we present additively manufactured porous magnesium structures that have the potential to satisfy all above-mentioned requirements. Even after 4 weeks of biodegradation, the mechanical properties of the porous structures were found to be within those reported for native bone. Moreover, our comprehensive electrochemical, mechanical, topological, and biological study revealed a unique biodegradation behavior and the limited cytotoxicity of the developed biomaterials.

The Role of Magnesium Ion Substituted Biphasic Calcium Phosphate Spherical Micro-Scaffolds in Osteogenic Differentiation of Human Adipose Tissue-Derived Mesenchymal Stem Cells.

This study was investigated the role of magnesium (Mg2+) ion substituted biphasic calcium phosphate (Mg-BCP) spherical micro-scaffolds in osteogenic differentiation of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs). Mg-BCP micro-scaffolds with spherical morphology were successfully prepared using in situ co-precipitation and spray drying atomization process. The in vitro cell proliferation and differentiation of hAT-MSCs were determined up to day 14. After in vitro biological tests, Mg-BCP micro-scaffolds with hAT-MSCs showed more enhanced osteogenicity than pure hAT-MSCs as control group by unique biodegradation of TCP phase and influence of substituted Mg2+ ion in biphasic nanostructure. Therefore, these results suggest that Mg-BCP micro-scaffolds promote osteogenic differentiation of hAT-MSCs.

The progress of biodegradable biliary stents

Biodegradable stents have achieved encouraging outcomes in the treatment of benign bile duct stenosis with good biocompatibility,unique biodegradation,and adept physical and mechanical performance.They have a higher biocompatibility than plastic and metal stents and do not require a second surgery for removal.This prevents adverse reactions like restenosis and the tendency to punch and bleed.These biodegradable stents provide a new method of treatment for biliary tract disease,and this review will focus on the animal experiments,clinical application,and future prospects of these stents. Key words: Bile duct diseases; Stents; Biocompatible materials

The effects of surface and biomolecules on magnesium degradation and mesenchymal stem cell adhesion

A novel class of biodegradable metals, magnesium (Mg) and Mg-based alloys, has recently attracted much attention because of unique biodegradation and mechanical properties for medical applications. Ideally, Mg-based devices should degrade no faster than the degradation products can be eliminated efficiently from the body. Additionally, for orthopedic and maxillofacial applications, the implant integration with the surrounding bone is critical for its clinical success. Therefore, it is necessary to thoroughly characterize Mg surface and degradation and investigate how these characteristics influence its interactions with essential cells, for example, bone marrow derived mesenchymal stem cells. The objectives of this study were to investigate (1) the effects of two surface conditions (the presence vs. absence of surface oxides) on Mg degradation and mesenchymal stem cell adhesion, and (2) the effects of two essential aqueous environments (the presence vs. absence of physiological ions and proteins) on Mg degradation. In an effort towards standardizing testing methods for Mg alloys, consistent and well-controlled experimental methods were designed to characterize the surface and degradation of Mg and its interactions with cells. The results demonstrated that original surface (oxidized vs. polished) conditions had a less pronounced effect on regulating initial cell adhesion, but did affect surface morphology and composition of the Mg samples after 24 h of cell culture. The presence versus absence of biological ions and proteins had a significant effect on Mg degradation mode and rate. In conclusion, the material surface and anatomical sites of implantation dependent on the intended applications must be carefully considered while assessing Mg alloys in vitro or in vivo for medical applications. Standardized testing procedures and methods are critically needed for developing more effective medical-grade Mg alloys.

A Cascade Biodegradable Polymer Based on Alternating Cyclization and Elimination Reactions

Polymers that depolymerize by a cascade of intramolecular reactions in response to the removal of a stabilizing end-cap can allow for an unprecedented degree of control over the polymer degradation process. Described here is the development of polymers comprising N,N'-dimethylethylenediamine and 4-hydroxybenzyl alcohol linked by carbamate linkages. The polycarbamate backbone is stable in aqueous solution, but removal of a protective end-cap from the amine terminus allows the diamine to cyclize, forming N,N'-dimethylimidazolidinone and releasing the phenol, which undergoes a 1,6-elimination followed by the release of CO(2) to reveal the next amine to continue the cascade. These polymers therefore degrade by alternating cyclization and elimination reactions. First, a tert-butylcarbamate (Boc) group was introduced as a cleavable end-cap, and the degradation kinetics and mechanism were studied by (1)H nuclear magnetic resonance (NMR) spectroscopy and size exclusion chromatography. Next, to demonstrate the degradability of these polymers under biologically relevant conditions, poly(ethylene oxide) was introduced as an end-cap via an ester linkage, to provide an amphiphilic block copolymer. This copolymer was found to assemble into cascade degradable nanoparticles that were capable of encapsulating and subsequently releasing a fluorescent dye in aqueous solution. This new class of polymers therefore provides highly promising materials that can be used for the development of medical devices, drug delivery vehicles, and tissue engineering scaffolds with unique biodegradation properties.