Aaron D. Puckett

Methacrylate-endcapped poly(d,l-lactide-co-trimethylene carbonate) oligomers. Network formation by thermal free-radical curing

Abstract A series of 3-arm, methacrylate-endcapped poly( d,l -lactide-co-trimethylene carbonate) prepolymers was synthesized using d,l -lactide:trimethylene carbonate (DLL:TMC) molar feed ratios of 100:0, 80:20, 60:40, 40:60, 20:80, and 0:100. Number average molecular weights were in the range (2.3–2.6) × 103 g mol−1. The prepolymers were free-radically crosslinked in the absence of reactive diluents to give amorphous, bioabsorbable networks with a broad range of thermal, mechanical, and degradative properties. Extraction studies indicated that sol-contents ranged from 2.89%–6.17%. Tensile modulus, ultimate strength, and Tg increased with increasing d,l -lactide content. Networks containing higher contents of d,l -lactide, 100:0, 80:20, and 60:40 (DLL:TMC), were strong and fairly rigid, but failed catastrophically at the yield point; networks containing lower contents of d,l -lactide, 20:80 and 0:100, showed a higher elongation to break, failing catastrophically at the yield point. A 40:60 DLL:TMC network fit perfectly within the series of compositions with regard to modulus and tensile strengh; however, it showed a yield point, followed by a regime of plastic flow prior to break. Hydrolytic degradation experiments revealed that the network based on poly( d,l -lactide) homopolymer degraded fastest owing to its hydrophilicity. Hydrolytic degradation in the copolymer networks was controlled by two opposing effects which occurred as the trimethylene carbonate was increased: Tg depression, which increased water uptake, and increased hydrophobicity, which decreased water uptake. Increasing trimethylene carbonate in the 80:20 and 60:40 DLL:TMC copolymer networks caused a decrease in the water uptake and the degradation rate since these network are both glassy at the degradation temperature of 37°C. The observed increase in degradation rate in the 40:60 copolymer network was due to increased water uptake caused by depression of the Tg to a value below the test temperature of 37°C. The 20:80 and 0:100 DLL:TMC networks were the slowest to degrade owing to their hydrophobicity.

Synthesis of Bioabsorbable Networks From Methacrylate-Endcapped Polyesters

A low-molecular-weight poly(e-caprolactone) triol (Mn = 540) was reacted with an excess of methacryloyl chloride to give a 3-arm methacrylate-endcapped polyester. The loss of the hydroxyl endgroups, which are capable of hydrogen bonding, lowered the viscosity of the polymer, thus enabling the formation of networks without solvent processing. The prepolymer was free radically homopolymerized, and copolymerized with methyl methacrylate, styrene, and 2-methylene-1,3-dioxepane to give a series of twelve biodegradable networks. Extraction studies indicated substantial network formation for all of the networks except those in which 2-methylene-1,3-dioxepane was used as the reactive diluent. A series of three low-molecular-weight poly(d,l-lactide) triols (Mn < 10 000) was synthesized by the trimethylolpropane-initiated ring-opening polymerization of d,l-lactide. Number-average molecular weights of the triols were estimated to be 2300, 5100, and 8700, by using gel permeation chromatography (g.p.c.), calibrated with polystyrene standards. The triols were reacted with excess methacryloyl chloride to produce a series of low-molecular-weight 3-arm methacrylate-endcapped polyesters. These prepolymers were free radically homopolymerized, and copolymerized with methyl methacrylate and styrene to give a series of twenty-seven biodegradable networks. Extraction studies indicated substantial network formation for all of these systems. The Tg values of each of the three homopolymer networks were higher than the corresponding Tg values of either of their respective copolymer networks, thus illustrating substantial network formation in the absence of reactive diluents. The ultimate strengths and tensile modulii of the homopolymer networks synthesized from the higher-molecular-weight prepolymers (Mn = 5100 and 8700) were higher than those measured for corresponding copolymer networks.

Synthesis of amino acid-containing polyacids and their application in self-cured glass-ionomer cement

Abstract Six methacrylate or acrylate derivatives of natural amino acids were synthesized and characterized. Based upon these monomers, six terpolymers [poly(acrylic) acid-co-itaconic acid-co-amino acid] were prepared and characterized. The synthesized polymers were used to formulate glass-ionomer cements (GICs) using Fuji II glass filler. The effects of the molecular weight (MW) and powder/liquid (P/L) ratio were evaluated. Scanning electron microscopy (SEM) was used to examine the fracture surfaces of the selected cement specimens. Results show that all the amino acid modified GICs exhibited higher compressive strengths (CS, 193–236 MPa) and much higher flexural strengths (FS, 55–71 MPa) as compared to commercial Fuji II GIC (191 in CS and 16 in FS). Both MW and P/L ratio affected the strength of the formed cement. It was important to find the optimal MW and P/L ratio to obtain the highest FS. In this study, optimized MW (number average) of the polyacids and P/L ratio were around 50,000 and 2.7/1, respectively. The microstructures of the fracture surfaces helped to explain the strength differences among the materials tested in the study. SEM analysis suggests that more integrated microstructures and fewer defects can lead to higher FS.

Preparation and characterization of novel elastin‐like polypeptide‐collagen composites

Collagen-based biomaterials suffer from poor mechanical properties and rapid degradation. Elastin-like polypeptides (ELPs) possess good biocompatibility and have unique solution properties that allow them to coacervate above a critical temperature. The objective of this research was to prepare a series of freeze dried ELP-collagen composite scaffolds as a proof of concept. Combination of ELP and collagen has the potential to produce composite structures with varying strengths. Four different composite structures were prepared by varying the ratio of ELP to collagen. Increased ELP content in the scaffolds appears to have reduced the residual water content based on Fourier transformed infrared spectroscopy and differential scanning calorimetry. Scanning electron microscopy images of ELP-collagen composites showed a three-dimensional, open porous structure with the formation of characteristic aggregates of ELP. The mechanical testing experiments showed that the elastic modulus, tensile strength, and toughness of ELP-collagen scaffolds were significantly greater than neat collagen scaffolds. The improved mechanical properties were attributed to a homogeneous network structure with additional reinforcement coming from the ELP aggregates. Our study confirms that ELP-collagen composites with superior physical and mechanical properties compared to collagen scaffolds can be produced. Further optimization of design parameters will allow producing ELP-collagen composites for specific biomedical applications.

Synthesis and formulation of vinyl-containing polyacids for improved light-cured glass-ionomer cements

Vinyl-containing poly(acrylic acid-co-itaconic acid) copolymers were synthesized and used to formulate light-curable cements containing reactive glass fillers (Fuji II LC). The conditions for light curing were studied and optimized. Effects of molecular weight (MW), grafting ratio, comonomer, liquid composition, powder/liquid (P/L) ratio, glass powder and aging were evaluated. The results show that the vinyl-containing glass-ionomer cements (GICs) prepared in this study exhibit higher compressive strength (CS, 225.6 MPa), diametral tensile strength (DTS, 28.4 MPa) and much higher flexural strength (FS, 116.4 MPa), as compared to commercial Fuji II LC GIC (186.6 in CS, 19.1 in DTS and 57.1 in FS). The optimal light-exposure time was found to be around 10 min, and concentrations of CQ and DC were 0.5% (by weight) and 1.0%, respectively. Effects of MW, grafting ratio, P/L ratio and content of polymer in the liquid formulation were significant. The highest strengths were found for the optimal formulations where the MW was 15,000 (weight average), grafting ratio 25 mol%, P/L ratio 2.7 and liquid composition 50:20:30. During aging, the cement showed an increase of strength over the first week and then no change for a month. SEM analysis suggests that more integrated microstructures and smaller glass particles can lead to higher FS and higher polymer content in GICs leads to tough fracture surface and plastic deformation.

Morphometric Evaluation of Tissue-Implant Reaction Associated With ALCAP and TCP Bioceramics In Vivo

The purpose of this investigation was to correlate the thickness of the fibrous capsule and the various histological components surrounding aluminum-calcium phosphate (ALCAP) and tricalcium phosphate (TCP) bioceramics at the subcutaneous (sc) and intraperitoneal (ip) implantation sites. The rational of conducting this investigation is to further elucidate the mechanisms of tissue-implant interaction. Thirteen Sprague-Dawley adult male albino rats were randomly divided into three groups. Animals in groups I and II (n = 5/group) were implanted at both ip and sc implantation sites with either ALCAP or TCP ceramics, respectively. Animals in group III (n

Syntheses and evaluation of biodegradable multifunctional polymer networks

Abstract The biodegradable, injectable and in situ crosslinkable polymer networks based upon di(propylene fumarate)–dimethacrylate (DPFDMA) and polycaprolactone trimethacrylate (PCLTMA), were prepared and characterized. The polymer networks were initiated by photopolymerization. The initial compressive (CS) and diametral tensile strengths (DTS) of the networks materials were determined and used to evaluate the effects of PCLTMA/DPFDMA ratios on the degradation behavior. The networks exhibited initial DTS values ranging from 2.5 to 9.3 MPa and CS values ranging from 1.8 to 146.0 MPa. The increase of PCLTMA in the formulation led to an increase in viscosity and DTS. The degree of conversions and polymerization shrinkage of the resins ranged from 60% to 72% and 5.1% to 6.4%, respectively. After 6 month, PCL300TMA/DPFDMA resins at a ratio of 100/0, 75/25 and 25/75 lost 70%, 87% and 46% of their initial CS, respectively, while PCL900TMA/DPFDMA and PCL300TMA/PCL900TMA resins at 75/25 lost 100% and 83% of their initial CS, respectively.

Cytological evaluation of the tissue-implant reaction associated with S/C and I/P implantation of ALCAP and HA bioceramics in vivo.

It is well documented that several ceramic materials are highly compatible and non-immunogenic with host tissues. Recent studies have demonstrated the need for further investigation of these devices in vivo to further elucidate the possible mechanisms involved in biocompatibility. The purpose of this investigation was to study the morphological characteristics of the fibrous tissue capsule resulting from the implantation of aluminum calcium phosphate (ALCAP) and hydroxyapetite (HA) bioceramics. Implants of ALCAP and HA were implanted into 10 adult male rats subcutaneously (S/C) and intraperitoneally (I/P). At 90 days post-implantation, the animals were euthanized, and the ceramic devices, the fibrous tissue, and vital organs were harvested. Evaluation of routine stained sections (5 microm, hematoxylin & eosin) of the fibrous tissue capsule surrounding the HA and ALCAP ceramics revealed the following: 1) all the ceramic devices had fibrous connective tissue capsules of slightly varying degrees of thickness at the time of sacrifice, depending on the site of implantation and type of material, and 2) there were statistically significant differences (p < 0.05) in the numbers and types of cellular components with respect to implantation site. The number of macrophages, neutrophils, fibroblasts, degree of vascularity, and thickness of the fibrous tissue matrix was found to be statistically different between the S/C implanted ceramic groups. The number of macrophages, neutrophils, fibroblasts, and collagen content comparing the fibrous tissue surrounding the ALCAP and HA ceramics (I/P), was found to be statisically different.

Syntheses and evaluation of novel biodegradable amino acid based anhydride polymer resins and composites

Abstract A novel synthetic biodegradable oligomer based upon methacrylated aminocaproyl maleamic acid (MACMA), was synthesized and characterized. Injectable and in situ crosslinkable polymer networks were formulated by copolymerization of MACMA with triethyleneglycol dimethacrylate (TEGDMA). In addition, composites composed of MACMA, TEGDMA and beta-tricalcium phosphate ( β -TCP) were prepared. The networks and composites were initiated by photo- and redox-polymerization, respectively. The initial compressive (CS) and diametral tensile strengths (DTS) of these materials were determined and used to evaluate the effects of MACMA/TEGDMA ratios on the degradation behavior of the materials. The neat resin networks exhibited initial CS values ranging from 6.7 to 284.2 MPa and the composites demonstrated initial DTS values ranging from 2.8 to 20.8 MPa and CS values ranging from 19.1 to 119.5 MPa. During the course of degradation the polymer neat resins lost 51%, 69% and 61% of their initial CS after 3 weeks for the MACMA/TEGDMA ratios at 25/75, 50/50 and 75/25, respectively. The resin with the MACMA/TEGDMA ratio of 75/25 completely degraded after 6 months. The composite with the MACMA/TEGDMA ratio of 25/75 exhibited a significant increase in CS after an initial decrease for 7 days and then lost 57% of its initial CS after 3 months. The composite composed of poly(MACMA) homopolymer showed a complete degradation after 21 days.

NANO AND MICRO-STRUCTURES OF ELASTIN-LIKE POLYPEPTIDE-BASED MATERIALS AND THEIR APPLICATIONS: RECENT DEVELOPMENTS

Elastin-like polypeptide (ELP) containing materials have spurred significant research interest for biomedical applications exploiting their biocompatible, biodegradable and nonimmunogenic nature while maintaining precise control over their chemical structure and functionality through genetic engineering. Physical, mechanical and biological properties of ELPs could be further manipulated using genetic engineering or through conjugation with a variety of chemical moieties. These chemical and physical modifications also achieve interesting micro- and nanostructured ELP-based materials. Here, we review the recent developments during the past decade in the methods to engineer elastin-like materials, available genetic and chemical modification methods and applications of ELP micro and nanostructures in tissue engineering and drug delivery.