[Show abstract][Hide abstract] ABSTRACT: Citrate-based polymers possess unique advantages for various biomedical applications since citric acid is a natural metabolism product, which is biocompatible and antimicrobial. In polymer synthesis, citric acid also provides multiple functional groups to control the crosslinking of polymers and active binding sites for further conjugation of biomolecules. Our group recently developed a number of citrate-based polymers for various biomedical applications by taking advantage of their controllable chemical, mechanical, and biological characteristics. In this study, various citric acid derived biodegradable polymers were synthesized and investigated for their physicochemical and antimicrobial properties. Results indicate that citric acid derived polymers reduced bacterial proliferation to different degrees based on their chemical composition. Among the studied polymers, poly(octamethylene citrate) showed ~70-80% suppression to microbe proliferation, owing to its relatively higher ratio of citric acid contents. Crosslinked urethane-doped polyester elastomers and biodegradable photoluminescent polymers also exhibited significant bacteria reduction of ~20 and ~50% for Staphylococcus aureus and Escherichia coli, respectively. Thus, the intrinsic antibacterial properties in citrate-based polymers enable them to inhibit bacteria growth without incorporation of antibiotics, silver nanoparticles, and other traditional bacteria-killing agents suggesting that the citrate-based polymers are unique beneficial materials for wound dressing, tissue engineering, and other potential medical applications where antimicrobial property is desired.
Full-text · Article · Jul 2014 · Frontiers in Bioengineering and Biotechnology
[Show abstract][Hide abstract] ABSTRACT: A method of introducing intrinsically photoluminescent properties to biodegradable polymer is introduced, exemplified by the synthesis of intrinsically photoluminescent polylactones that enable non-invasively monitoring and tracking material degradation in vivo in real-time and the formation of theranostic nanoparticles for cancer imaging and drug delivery.
[Show abstract][Hide abstract] ABSTRACT: Amphiphilic biodegradable photoluminescent polymers (ABPLPs) composed of a biodegradable fluorescent polymer and methoxy poly (ethyleneglycol) demonstrate intrinsic bright, tunable, and stable fluorescence emission. ABPLP micelles elicit minor cellular toxicity and can be used for cell and tissue imaging both in vitro and in vivo.
[Show abstract][Hide abstract] ABSTRACT: The field of tissue engineering and drug delivery calls for new measurement tools, non-invasive real-time assays, and design methods for the next wave of innovations. Based on our recent progress in developing intrinsically biodegradable photoluminescent polymers (BPLPs) without conjugating organic dyes or quantum dots, in this paper, we developed a new type urethane-doped biodegradable photoluminescent polymers (UBPLPs) that could potentially serve as a new tool to respond the above call for innovations. Inherited from BPLPs, UBPLPs demonstrated strong inherent photoluminescence and excellent cytocompatibility in vitro. Crosslinked UBPLPs (CUBPLPs) showed soft, elastic, but strong mechanical properties with a tensile strength as high as 49.41 ± 6.17 MPa and a corresponding elongation at break of 334.87 ± 26.31%. Porous triphasic CUBPLP vascular scaffolds showed a burst pressure of 769.33 ± 70.88 mmHg and a suture retention strength of 1.79 ± 0.11 N. Stable but photoluminescent nanoparticles with average size of 103 nm were also obtained by nanoprecipitation. High loading efficiency (91.84%) and sustained release of 5-fluorouracil (up to 120 h) were achieved from UBPLP nanoparticles. With a quantum yield as high as 38.65%, both triphasic scaffold and nanoparticle solutions could be non-invasively detected in vivo. UBPLPs represent an innovation in fluorescent biomaterial design and may offer great potential in advancing the field of tissue engineering and drug delivery where bioimaging has gained increasing interest.
[Show abstract][Hide abstract] ABSTRACT: The marriage of biodegradable polymer and fluorescent imaging has resulted in an important area of polymeric biomaterials: biodegradable fluorescent polymers. Researchers have put significant efforts on developing versatile fluorescent biomaterials due to their promising in biological/biomedical labeling, tracking, monitoring, imaging, and diagnostic applications, especially in drug delivery, tissue engineering, and cancer imaging applications. Biodegradable fluorescent polymers can function not only as implant biomaterials but also as imaging probes. Currently, there are two major classes of biodegradable polymers used as fluorescent materials. The first class is the combination of non-fluorescent biodegradable polymers and fluorescent agents such as organic dyes and quantum dots. Another class of polymers shows intrinsic photoluminescence as polymers by themselves carrying integral fluorescent chemical structures in or pendent to their polymer backbone, such as Green Fluorescent protein (GFP), and the recently developed biodegradable photoluminescent polymer (BPLP). Thus there is no need to conjugate or encapsulate additional fluorescent materials for the latter. In the present review, we will review the fluorescent biodegradable polymers with emphases on material fluorescence mechanism, design criteria for fluorescence, and their cutting-edge applications in biomedical engineering. We expect that this review will provide insightful discussion on the fluorescent biomaterial design and lead to innovations for the development of the next generation of fluorescent biomaterials and fluorescence-based biomedical technology.
Preview · Article · Jan 2013 · Journal of Materials Chemistry B
[Show abstract][Hide abstract] ABSTRACT: The development of dual-imaging enabled cancer-targeting nanoparticles (DICT-NPs) is reported based on newly developed biodegradable photoluminescent polymers and superparamagnetic iron oxide nanoparticles. DICT-NPs possess capabilities of dual-imaging (magnetic resonance imaging and optical imaging), magnetic targeting, and potentially selective targeting for cancer cells. The development of DICT-NPs address the concerns in dual-imaging nanoparticles where photobleaching organic dyes and cytotoxic quantum dots are usually adopted.
[Show abstract][Hide abstract] ABSTRACT: In this study, two novel ionic liquid matrices (ILMs), N,N-diisopropylethylammonium 3-oxocoumarate and N,N-diisopropylethylammonium dihydroxymonooxoacetophenoate, were tested for the structural elucidation of recently developed aliphatic biodegradable polymers by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). The polymers, formed by a condensation reaction of three components, citric acid, octane diol, and an amino acid, are fluorescent, but the exact mechanism behind their luminescent properties has not been fully elucidated. In the original studies, which introduced the polymer class (J. Yang et al., Proc. Natl. Acad. Sci. USA 2009, 106, 10086-10091), a hyper-conjugated cyclic structure was proposed as the source for the photoluminescent behavior. With the use of the two new ILMs, we present evidence that supports the presence of the proposed cyclization product. In addition, the new ILMs, when compared with a previously established ILM, N,N-diisopropylethylammonium α-cyano-3-hydroxycinnimate, provided similar signal intensities and maintained similar spectral profiles. This research also established that the new ILMs provided good spot-to-spot reproducibility and high ionization efficiency compared with corresponding crystalline matrix preparations. Many polymer features revealed through the use of the ILMs could not be observed with crystalline matrices. Ultimately, the new ILMs highlighted the composition of the synthetic polymers, as well as the loss of water that was expected for the formation of the proposed cyclic structure on the polymer backbone.
Preview · Article · May 2011 · Rapid Communications in Mass Spectrometry
[Show abstract][Hide abstract] ABSTRACT: Finding an ideal biomaterial with the proper mechanical properties and biocompatibility has been of intense
focusin the field ofsoft tissue engineering. This paperreports on the synthesis and characterization of a novel
crosslinked urethane-doped polyester elastomer(CUPOMC), which wassynthesized by reacting a previously
developed photocrosslinkable poly (octamethylene maleate citrate) (POMC) prepolymers (pre-POMC) with
1,6-hexamethylene diisocyanate (HDI) followed by thermo- or photo-crosslinking polymerization. The mechanical properties of the CUPOMCs can be tuned by controlling the molar ratios of pre-POMC monomers,
and the ratio between the prepolymer and HDI. CUPOMCs can be crosslinked into a 3D network through
polycondensation or free radical polymerization reactions. The tensile strength and elongation at break of
CUPOMC synthesized under the known conditions range from 0.73±0.12MPa to 10.91±0.64MPa and from
support cell adhesion and proliferation. Unlike the pre-polymers of other crosslinked elastomers, CUPOMC
pre-polymers possess great processability demonstrated by scaffold fabrication via a thermally induced phase
separation method. The dual crosslinking methods for CUPOMC pre-polymers should enhance the versatile
of available biodegradable elastomers for various biomedical applications such as soft tissue engineering
[Show abstract][Hide abstract] ABSTRACT: Finding an ideal biomaterial with the proper mechanical properties and biocompatibility has been of intense focus in the field of soft tissue engineering. This paper reports on the synthesis and characterization of a novel crosslinked urethane-doped polyester elastomer (CUPOMC), which was synthesized by reacting a previously developed photocrosslinkable poly (octamethylene maleate citrate) (POMC) prepolymers (pre-POMC) with 1,6-hexamethylene diisocyanate (HDI) followed by thermo- or photo-crosslinking polymerization. The mechanical properties of the CUPOMCs can be tuned by controlling the molar ratios of pre-POMC monomers, and the ratio between the prepolymer and HDI. CUPOMCs can be crosslinked into a 3D network through polycondensation or free radical polymerization reactions. The tensile strength and elongation at break of CUPOMC synthesized under the known conditions range from 0.73±0.12MPa to 10.91±0.64MPa and from 72.91±9.09% to 300.41±21.99% respectively. Preliminary biocompatibility tests demonstrated that CUPOMCs support cell adhesion and proliferation. Unlike the pre-polymers of other crosslinked elastomers, CUPOMC pre-polymers possess great processability demonstrated by scaffold fabrication via a thermally induced phase separation method. The dual crosslinking methods for CUPOMC pre-polymers should enhance the versatile processability of the CUPOMC used in various conditions. Development of CUPOMC should expand the choices of available biodegradable elastomers for various biomedical applications such as soft tissue engineering.
[Show abstract][Hide abstract] ABSTRACT: Herein, we report a first citric acid (CA)-derived in situ crosslinkable biodegradable polymer, poly(ethylene glycol) maleate citrate (PEGMC). The synthesis of PEGMC could be carried out via a one-pot polycondensation reaction without using organic solvents or catalysts. PEGMC could be in situ crosslinked into elastomeric PPEGMC hydrogels. The performance of hydrogels in terms of swelling, degradation, and mechanical properties were highly dependent on the molar ratio of monomers, crosslinker concentration, and crosslinking mechanism used in the synthesis process. Cyclic conditioning tests showed that PPEGMC hydrogels could be compressed up to 75% strain without permanent deformation and with negligible hysteresis. Water-soluble PEGMC demonstrated excellent cytocompatibilty in vitro. The degradation products of PPEGMC also showed minimal cytotoxicity in vitro. Animal studies in rats clearly demonstrated the excellent injectability of PEGMC and degradability of the in situ-formed PPEGMC. PPEGMC elicited minimal inflammation in the early stages post-injection and was completely degraded within 30 days in rats. In conclusion, the development of CA-derived injectable biodegradable PEGMC presents numerous opportunities for material innovation and offers excellent candidate materials for in situ tissue engineering and drug delivery applications.
[Show abstract][Hide abstract] ABSTRACT: Creating heterogeneous tissue constructs with an even cell distribution and robust mechanical strength remain important challenges to the success of in vivo tissue engineering. To address these issues, we are developing a scaffold sheet tissue engineering strategy consisting of thin (∼200 μm), strong, elastic, and porous crosslinked urethane-doped polyester (CUPE) scaffold sheets that are bonded together chemically or through cell culture. Suture retention of the tissue constructs (four sheets) fabricated by the scaffold sheet tissue engineering strategy is close to the surgical requirement (1.8 N) rendering their potential for immediate implantation without a need for long cell culture times. Cell culture results using 3T3 fibroblasts show that the scaffold sheets are bonded into a tissue construct via the extracellular matrix produced by the cells after 2 weeks of in vitro cell culture.
[Show abstract][Hide abstract] ABSTRACT: None of the current biodegradable polymers can function as both implant materials and fluorescent imaging probes. The objective of this study was to develop aliphatic biodegradable photoluminescent polymers (BPLPs) and their associated cross-linked variants (CBPLPs) for biomedical applications. BPLPs are degradable oligomers synthesized from biocompatible monomers including citric acid, aliphatic diols, and various amino acids via a convenient and cost-effective polycondensation reaction. BPLPs can be further cross-linked into elastomeric cross-linked polymers, CBPLPs. We have shown representatively that BPLP-cysteine (BPLP-Cys) and BPLP-serine (BPLP-Ser) offer advantages over the traditional fluorescent organic dyes and quantum dots because of their preliminarily demonstrated cytocompatibility in vitro, minimal chronic inflammatory responses in vivo, controlled degradability and high quantum yields (up to 62.33%), tunable fluorescence emission (up to 725 nm), and photostability. The tensile strength of CBPLP-Cys film ranged from 3.25 +/- 0.13 MPa to 6.5 +/- 0.8 MPa and the initial Modulus was in a range of 3.34 +/- 0.15 MPa to 7.02 +/- 1.40 MPa. Elastic CBPLP-Cys could be elongated up to 240 +/- 36%. The compressive modulus of BPLP-Cys (0.6) (1:1:0.6 OD:CA:Cys) porous scaffold was 39.60 +/- 5.90 KPa confirming the soft nature of the scaffolds. BPLPs also possess great processability for micro/nano-fabrication. We demonstrate the feasibility of using BPLP-Ser nanoparticles ("biodegradable quantum dots") for in vitro cellular labeling and noninvasive in vivo imaging of tissue engineering scaffolds. The development of BPLPs and CBPLPs represents a new direction in developing fluorescent biomaterials and could impact tissue engineering, drug delivery, bioimaging.
Full-text · Article · Jul 2009 · Proceedings of the National Academy of Sciences
[Show abstract][Hide abstract] ABSTRACT: Biodegradable elastomers have recently found widespread application in many areas of biomedical engineering
such as tissue engineering, drug delivery, and bioimaging. In particular, the recent developments in research have led to
the creation of citric acid based polymers with enhanced mechanical properties, novel design strategies for crosslinking,
nanoporous features, and unique photoluminescent capabilities. The present review will cover the recent patents involving
citric acid derived biodegradable biomaterials within the field of biomedical engineering including poly (diol citrates) and
their composites, crosslinked urethane-doped polyesters (CUPEs), poly (alkylene maleate citrates) (PAMCs), poly
(xylitol-co-citrates) (PXC), and aliphatic biodegradable photoluminescent polymers (BPLPs). The synthesis,
development, and applications of these novel polymers will be discussed along with the current trends and future developments in the biomaterials field.
Full-text · Article · Feb 2009 · Recent Patents on Biomedical Engineering