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Resorbable materials of poly(L-lactide). VII. In vivo and in vitro degradation
Abstract
In vivo and in vitro degradation of high molecular weight poly(L-lactide) used for internal bone fixation has been investigated. Within 3 months as-polymerized, microporous PLLA (Mv = 6.8-9.5 X 10(5] exhibited a massive strength-loss (sigma b = 68-75 MPa to sigma b = 4 MPa) and decrease of Mv (90-95%). At week 39, the first signs of resorption were evident (mass-loss 5 wt%). Except for dynamically loaded bone plates no differences between in vivo and in vitro degradation of PLLA were observed. The increase of crystallinity of PLLA upon degradation (up to 83%) is likely to be attributed to recrystallization of tie-chain segments. A more ductile PLLA exhibiting a lower rate of degradation was prepared by extraction of low molecular weight compounds with ethyl acetate.
... The mechanical properties of PLA deteriorate by hydrolysis in moisture and enzymatic action, and ultimately the material degrades into carbon dioxide and water [9,10]. These characteristics have been used to advantage in eco-friendly green plastics and medical tools such as bone setter bolts and pins [12,[15][16][17][18][19][20][21]. ...
... The deterioration of the mechanical properties of PLA has been evaluated both in vivo [11,12,[17][18][19][20][21]26] and in vitro [11,17,19,26] in research on bone setting bolts or pins. The strengths of fabricated PLA structures have been evaluated by tensile tests [14,17,19,27], flexural tests [17,28], and shear tests [17] after heat degradation at 37 • C [17,19,26,28,29]. ...
... The deterioration of the mechanical properties of PLA has been evaluated both in vivo [11,12,[17][18][19][20][21]26] and in vitro [11,17,19,26] in research on bone setting bolts or pins. The strengths of fabricated PLA structures have been evaluated by tensile tests [14,17,19,27], flexural tests [17,28], and shear tests [17] after heat degradation at 37 • C [17,19,26,28,29]. ...
A fused filament fabrication (FFF) 3D printer is a simple device capable of manufacturing three-dimensional structures in a series of easy steps. Commercial-level FFF 3D printers have spread rapidly in many fields in recent years. Poly(lactic acid) (PLA) is a biodegradable thermoplastic polymer used as a typical printing medium for FFF 3D printers. The FFF printer constructs an object with melted polymer extruded from a tiny scanning nozzle. The mechanical properties of FFF 3D structures printed with different scan patterns can therefore vary in accordance with the directions from which forces act upon them. The nozzle scan pattern also influences the deterioration of the mechanical properties of the structures in accordance with the degradation caused by the hydrolysis of PLA. In this study we conducted tensile tests to evaluate the strength characteristics of 3D printed test pieces formed from PLA using four different scan patterns: parallel, vertical, parallel-and-vertical, and cross-hatched at opposing diagonal angles to the tensile direction. We also formed test pieces by an injection molding method using the same material, for further comparison. We evaluated the deterioration of the test pieces after immersing them in saline for certain periods. After the test pieces formed by different nozzle scan patterns were immersed, they exhibited differences in the rates by which their maximum tensile stresses deteriorated and their masses increased through water uptake. The influences of the scan patterns could be classified into two types: the unidirectional scan pattern influence and bidirectional scan pattern influence. The data obtained in this research will be applied to structural design when the FFF 3D printer is employed for the fabrication of structures with PLA filament.
... PEG precursors were functionalized with methacrylic acid groups as well as hydrophobic PLA-units (PEG-PLLA-DMA) to enable a faster degradation by hydrolysis of ester-bonds in vivo [227]. As references, only slightly degradable PEG-DMAs with either low (PEG-DMAlmw) or high (PEG-DMAhmw) molecular weight were used and added in different mass percentages (10-50 wt%) to the cement liquid. ...
... Slightly degradable PEG-DMA with either low (PEG-DMAlmw) or high (PEG-DMAhmw) molecular weight were used as hydrogel precursors in comparison to a degradable gelation system obtained by incorporation of hydrophobic PLA-units with several ester functions (PEG-PLLA-DMA). The latter is known to show a faster degradation by hydrolysis of the ester-bonds in vivo[227]. The amount of hydrogel was varied in the range of 10 to 50 wt% referred to the used cement liquid. ...
Synthetic bone replacement materials have their application in non-load bearing defects with the function of (re-)construction or substitution of bone. This tissue itself represents a biological composite material based on mineralized collagen fibrils and combines the mechanical strength of the mineral with the ductility of the organic matrix. By mimicking these outstanding properties with polymer-cement-composites, an imitation of bone is feasible. A promising approach for such replacement materials are dual setting systems, which are generated by dissolution-precipitation reaction with cement setting in parallel to polymerization and gelation of the organic phase forming a coherent hydrogel network. Hereby, the high brittleness of the pure inorganic network was shifted to a more ductile and elastic behavior. The aim of this thesis was focused on the development of different dual setting systems to modify pure calcium phosphate cements’ (CPCs’) mechanical performance by incorporation of a hydrogel matrix. A dual setting system based on hydroxyapatite (HA) and cross-linked 2-hydroxyethyl methacrylate (HEMA) via radical polymerization was advanced by homogenous incorporation of a degradable cross-linker composed of poly(ethylene glycol) (PEG) as well as poly(lactic acid) (PLA) with reactive terminal methacrylate functionalities (PEG-PLLA-DMA). By integration of this high molecular weight structure in the HEMA-hydrogel network, a significant increase in energy absorption (toughness) under 4-point bending testing was observed. An addition of only 10 wt% hydrogel precursor (referred to the liquid phase) resulted in a duplication of stress over a period of 8 days. Additionally, the calculated elasticity was positively affected and up to six times higher compared to pure HA. With a constantly applied force during compressive strength testing, a deformation and thus strain levels of about 10 % were reached immediately after preparation. For higher degradability, the system was modified in a second approach regarding organic as well as inorganic phase. The latter component was changed by brushite forming cement that is resorbable in vivo due to solubility processes. This CPC was combined with a hydrogel based on PEG-PLLA-DMA and other dimethacrylated PEGs with different molecular weights and concentrations. Hereby, new reaction conditions were created including a shift to acidic conditions. On this ground, the challenge was to find a new radical initiator system. Suitable candidates were ascorbic acid and hydrogen peroxide. that started the polymerization and successful gelation in this environment. These highly flexible dual set composites showed a very high ductility with an overall low strength compared to HA-based models. After removal of the applied force during compressive strength testing, a complete shape recovery was observed for the samples containing the highest polymeric amount (50 wt%) of PEG-PLLA-DMA. Regarding phase distribution in the constructs, a homogenously incorporated hydrogel network was demonstrated in a decalcifying study with ethylenediaminetetraacetic acid. Intact, coherent hydrogels remained after dissolution of the inorganic phase via calcium ion complexation. In a third approach, the synthetic hydrogel matrix of the previously described system was replaced by the natural biopolymer gelatin. Simultaneously to brushite formation, physical as well as chemical cross-linking by the compound genipin was performed in the dual setting materials. Thanks to the incorporation of gelatin, elasticity increased significantly, in which concentrations up to 10.0 w/v% resulted in a certain cohesion of samples after compressive strength testing. They did not dissociate in little pieces but remained intact cuboid specimens though having cracks or fissures. Furthermore, the drug release of two active pharmaceutical ingredients (vancomycin and rifampicin) was investigated over a time frame of 5 weeks. The release exponent was determined according to Korsmeyer-Peppas with n = 0.5 which corresponds to the drug liberation model of Higuchi. A sustained release was observed for the antibiotic vancomycin encapsulated in composites with a gelatin concentration of 10.0 w/v% and a powder-to-liquid ratio of 2.5 g/mL. With respect to these developments of different dual setting systems, three novel approaches were successfully established by polymerization of monomers and cross-linking of precursors forming an incorporated, homogenous hydrogel matrix in a calcium phosphate network. All studies showed an essential transfer of mechanical performance in direction of flexibility and bendability.
... In vivo, the Lactic acid that is released by PLLA degradation is converted into glycogen in the liver or incorporated into the tricarboxylic acid cycle and excreted from the lungs as water and carbon dioxide [9]. Scaffolds fabricated for bone tissue engineering applications require specific material properties (porous architecture, adequate porosity levels and mechanical strength) and therefore L-PLA in preferred in the orthopedic applications because it satisfies most of these requirements [74,77,86,87]. Poly (L-lactic acid) (PLLA) has been investigated as a biomaterial and fabricated into scaffolds [88,249,250] by utilizing salt leaching [251], phase separation [252,253], and gas-induced foaming [77,254] methods. ...
... D,L-PLA owing to its fast degradation rate is strategically placed on the outside to promote biodegradation and replacement with new bone tissue. The PLLA degrades slowly Scaffolds fabricated for bone tissue engineering applications require specific material properties (porous architecture, adequate porosity levels and mechanical strength) and therefore L-PLA in preferred in the orthopedic applications because it satisfies most of these requirements [74,77,86,87]. Poly (L-lactic acid) (PLLA) has been investigated as a biomaterial and fabricated into scaffolds [88,249,250] by utilizing salt leaching [251], phase separation [252,253], and gas-induced foaming [77,254] methods. ...
This review discusses and summarizes the recent developments and advances in the use of biodegradable materials for bone repair purposes. The choice between using degradable and non-degradable devices for orthopedic and maxillofacial applications must be carefully weighed. Traditional biodegradable devices for osteosynthesis have been successful in low or mild load bearing applications. However, continuing research and recent developments in the field of material science has resulted in development of biomaterials with improved strength and mechanical properties. For this purpose, biodegradable materials, including polymers, ceramics and magnesium alloys have attracted Materials 2015, 8 5745 much attention for osteologic repair and applications. The next generation of biodegradable materials would benefit from recent knowledge gained regarding cell material interactions, with better control of interfacing between the material and the surrounding bone tissue. The next generations of biodegradable materials for bone repair and regeneration applications require better control of interfacing between the material and the surrounding bone tissue. Also, the mechanical properties and degradation/resorption profiles of these materials require further improvement to broaden their use and achieve better clinical results.
... The media chosen to perform the degradation studies was PBS. Although this solution does not replicate body fluid (the absence of enzymes that would be present in the host), studies in the past comparing the degradation profiles of polymers in PBS and in vivo found a close match [34][35][36]. ...
The creation of scaffolds for cartilage tissue engineering has faced significant challenges in developing constructs that can provide sufficient biomechanical support and offer suitable degradation characteristics. Ideally, such tissue-engineering techniques necessitate the fabrication of scaffolds that mirror the mechanical characteristics of the articular cartilage while degrading safely without damaging the regenerating tissues. The aim of this study was to create porous, biomechanically comparable 3D-printed scaffolds made from Poly(L-lactide-co-glycolide) 85:15 and to assess their degradation at physiological conditions 37 °C in pH 7.4 phosphate-buffered saline (PBS) for up to 56 days. Furthermore, the effect of scaffold degradation on the cell viability and proliferation of human bone marrow mesenchymal stem cells (HBMSC) was evaluated in vitro. To assess the long-term degradation of the scaffolds, accelerated degradation tests were performed at an elevated temperature of 47 °C for 28 days. The results show that the fabricated scaffolds were porous with an interconnected architecture and had comparable biomechanical properties to native cartilage. The degradative changes indicated stable degradation at physiological conditions with no significant effect on the properties of the scaffold and biocompatibility of the scaffold to HBMSC. Furthermore, the accelerated degradation tests showed consistent degradation of the scaffolds even in the long term without the notable release of acidic byproducts. It is hoped that the fabrication and degradation characteristics of this scaffold will, in the future, translate into a potential medical device for cartilage tissue regeneration.
... Characteristic attributes of bioceramics used in biomedical applications [6,7,[11][12][13][14][15][16][17][18][19][20][21][22]. Types Whereas, bioceramics are reported to form interfacial bonding with human bones and stimulate the composition of bones. ...
Bioceramics have been widely utilized for orthopaedic applications in which the biocompatibility and mechanical properties of the materials are vital characteristics to be considered for their clinical use. Till date, extensive studies have been devoted to developing a range of scientific ways for tailoring the microstructure of bioceramics in order to attain the trade-off of mechanical properties and biocompatibility of the final product. Owing to low reactivity, earlier stabilization and longer functional life of bioceramic, the developed implants are capable of replicating the mechanical behaviour of original bone. As the safety of the patient and its ultimate functionality are the ultimate goal of the selected implant material hence, the present literature survey investigates and brings forth the important aspects associated to the mechanical, biological and microstructural characteristics of bioceramics employed in orthopaedic applications. The review paper majorly focuses on effective utilization of various materials as an additive in bioceramics and processing techniques used for enhancement of properties, enabling the use of material in orthopaedic applications. The influence of various additives on the microstructure, mechanical properties and biological performance of developed bioceramics orthopaedic implants has been elaborately discussed. Furthermore, future prospects are proposed to promote further innovations in bioceramics research.
... PLA is recyclable, incinerable, and compostable. It also possesses bioabsorbablity, renewability, thermoplastic behavior (good shaping and molding capability), easy processability, low energy consumption, and low carbon emissions during its production [5][6][7]. PLA exhibits comparable mechanical and thermal performance as its petroleum-based polyester counterparts, and is even better than other biodegradable aliphatic polyesters [5,8]. ...
... They are seen replacing commodity packaging materials [15]. PLA can be hydrolysed to form non-toxic, harmless substances, such as CO 2 , water, methane, biomass humic matter and other natural substances [16][17][18][19]. The degradation of PLA and its composites occur in stages; the dispersion of water into the material, then hydrolysis of ester bonds and therefore dropping in the molecular weight. ...
The use of biodegradable polymers and their composites have wide
applications and high demands because they can be ideal alternatives to non-biodegradable polymers due to the growing global environmental concerns. The biodegradation of PLA and starch-based plastic composites by the use of enzymes was studied in commercial compost and soil.The composites were prepared from two biopolymers, i.e. polylactic acid (PLA) and starch, using Brabender 30 EHT mixer at the composition of 10:90, 25:75, 50:50, 75:25 and 90:10 (weight ratio) respectively, and then their degradability was investigated under controlled compost and soil burial laboratory conditions for 14 and 28 days. The degradation was measured throughout the period of the experiment by visual inspection,
gel permeation chromatography (GPC), thermal gravimetric analysis
(TGA), scanning electron microscopy (SEM), Fourier transform infrared
(FTIR), titration and gas chromatography (GC). GPC analysis confirmed that the molecular weight of PLA decreased due to degradation, while TGA analysis showed a lower thermal stability for the composites containing more starch. The visual inspection and SEM analysis revealed that the size of polymer composites reduced while the shape became less regular owing to the biodegradation. FTIR spectra of polymer composites showed strong carbonyl bands between 1750.9 cm-1-1760.2 cm-1 that became broader with a slight shift to higher wave number to 1756.1 cm-1-1763.7 cm-1 after degradation. Moreover, the addition of lipase into the compost and soil promoted the degradation rate of polymer composites, leading to the generation of more CO2 gas and more weight loss, compared to the experimental results obtained without the use of lipase. To conclude, the degradation rate of PLA/starch composites can be tailored by changing the composition and environmental conditions (such as temperature and the addition of enzymes).
... ∆H c , ∆H m , and Xc% decreased with degradation time, although some samples (10 wt % FeHA and 30 wt % FeHA) slightly increased crystallinity around the 12th week of degradation. This increase, discussed in the literature [15,[23][24][25][26][27], is attributed to the splitting of the chains, which as they shorten, reorder more easily and form crystals. Table 2. Parameters obtained by thermal analysis on the PLLA-FeHA system: dt (weeks) = degradation time in weeks, Tm = melting point ( • C), ∆Hm = melting enthalpy (kJ/kg), Tg = glass transition temperature ( • C), Tc = crystallization temperature ( • C), ∆Hc = crystallization enthalpy (kJ/kg), Xc = crystalline fraction (%), calculated as Xc% = 100 [(∆Hm1 − ∆Hcc)/∆Hm 0 ] with ∆Hm 0 = 93 J/g [16], CC = crystallization capacity (%), calculated as: CF % = 100(∆Hc/∆Hm1). ...
This work reports on the synthesis, with the thermally induced phase separation (TIPS) technique, of poly (l-lactide) (PLLA) scaffolds containing Fe-doped hydroxyapatite (FeHA) particles for bone regeneration. Magnetization curves and X-ray diffraction indicate two magnetic particle phases: FeHA and magnetite Fe3O4. Magnetic nanoparticles (MNPs) are approximately 30 ± 5 nm in width and 125 ± 25 nm in length, and show typical ferromagnetic properties, including coercivity and rapid saturation magnetization. Scanning electron microscopy (SEM) images of the magnetic scaffolds reveal their complex morphology changes with MNP concentration. Similarly, at compositions of approximately 20% MNPs, the phase separation changes, passing from solid–liquid to liquid–liquid as revealed by the hill-like structures, with low peaks that give the walls in the SEM images a surface pattern of micro-ruggedness typical of nucleation mechanisms and growth. In vitro degradation experiments, carried out for more than 28 weeks, demonstrated that the MNPs delay the scaffold degradation process. Cytotoxicity is appreciated for FeHA content above 20%.
... Dans le cas de la PCL, il y a formation de l'acide 6-hydroxyhexanoique, l'acide lactique est le résultat de dégradation de PLA et l'acide glycolique est obtenu par dégradation de PGA. Les étapes clés de la dégradation sont i) la dégradation de la partie amorphe qui tend à augmenter la cristallinité, sans entraîner de perte de masse en raison de l'absence de diffusion des chaînes rompues au sein de la matrice polymère 92 ; ii) la diminution importante de la masse de polymère par formation d'oligomères pouvant diffuser hors de la matrice polymère[106][107] . La dégradation hydrolytique des polyesters (PLA et PGA) est autocatalysée par les groupes carboxyles formés durant ce processus 108 .La PCL se dégrade sur des durées allant de quelques mois à quelques années en fonction de la masse molaire, des conditions de dégradation, ainsi que du degré de cristallinité91- 104 . ...
Depuis plusieurs décennies, les polyesters aliphatiques (polycaprolactone (PCL), polylactide (PLA), polyglycolide (PGA)) et leurs copolymères ont été retenus pour des applications médicales grâce à leur biodégradabilité et leur biocompatibilité. Parmi leurs applications médicales, on s’intéresse ici à la délivrance des médicaments par des copolymères amphiphiles et à l’ingénierie tissulaire. Les polyesters aliphatiques souffrent cependant d’une hydrophobie importante et de l’absence de groupes fonctionnels. Pour pallier ces problèmes, plusieurs stratégies demodifications chimiques ont été proposées dans la littérature parmi lesquelles on cite : l’hydrolyse, la modification par plasma, la post-polymérisation alcyne azoture et la modification photochimique thiol-yne. Ces modifications servent à introduire des polymères hydrophiles (ex. le polyéthylène glycol) ou des groupes fonctionnels qui peuvent améliorer la biocompatibilité de polyesters. Dans ce manuscrit, on s’intéresse à la modification de la PCL et du PLA par voie photochimique thiol-yne qui présente l’avantage d’être rapide, versatile, applicable en solution comme en surface et de ne pas nécessiter l’utilisation d’un catalyseur métallique qui peut être nocif pour les applications médicales. Dans une première partie, la modification de la PCL a été faite en solution et des copolymères amphiphiles PCL-g-PEG ont été synthétisés. La stratégie de greffage « grafting to » en deux étapes a été choisie en partant de polymères commerciaux. Une optimisation des conditions de modification par voie anionique de PCL, suivi d’une photoaddition thiol-yne, nous a permis d’obtenir des copolymères avec des balances hydrophiles/hydrophobes contrôlées. L’impact de l’hydrophilie des copolymères sur la formation de nanoobjets, leurs concentrations d’aggrégation critique et leurs tailles a été étudié. L’encapsulation de curcumine comme agent anticancéreux et la cytotoxicité des nanovecteurs envers des cellules cancéreuses ont été vérifiées. Dans un second temps, ces copolymères ont été décorés par un peptide de ciblage et un peptide clivable enzymatiquement en vue de leur utilisation dans des traitements anticancéreux. L’effet biologique de ces copolymères encapsulant des principes actifs est vérifié in vitro sur des cellules cibles exprimant plus ou moins d’intégrines ou de métalloprotéases. Dans une seconde partie, des fibres PLA ont été modifiées en surface par des nanoparticules inorganiques afin de générer des hybrides covalents d’intérêts pour des applications en ingénierie tissulaire. De manière analogue aux modifications en solution, ces hybrides ont été obtenus en deux étapes par modification par voie anionique de nanofibres de PLA, suivi par un greffage covalent de nanoparticules d’oxyde de fer en suivant une stratégie photochimique thiol-yne.
... [20][21][22] The material has many outstanding properties, such as biodegradability, biocompatibility, bioabsorbablity, thermoplastic behaviors, and ease of processability. [23][24][25][26] Therefore, PLA attracts considerable attention as a sustainable alternative to traditional non-degradable petrochemical-derived polymers. Its applications are broad from environmental, packaging, cosmetics, to biomedical fields. ...
Standard techniques for quantitative measurement of polyacrylamide (PAm) contents grafted on polylactide (PLA) film substrates, P(LA-g-Am-co-MBAm), which are commonly used as cell culture substrates or scaffolds, and pH-sensitive absorbents have been developed with X-ray photoelectron (XPS), proton-nuclear magnetic resonance (¹H-NMR), and Fourier transform infrared (FT-IR) spectroscopy. The techniques are then applied to examine P(LA-g-Am-co-MBAm) samples prepared from two separate photo-initiator/co-initiator systems. Efficiency and accuracy of the techniques are compared. The results from all techniques are in good agreement, indicating high analysis precisions, although FT-IR technique provides additional advantages, in terms of short analysis time, ease of sample preparation, and accessibility of a machine. The results indicate that the riboflavin (RF) initiator system has higher grafting efficiency than its camphorquinone (CQ) counterpart. These standard techniques can be applied in the analysis of these materials and further modified for quantitative analysis of other grafting systems.
... The degradation type of POC and PLLA are both hydrolytic degradation [2,28]. The hydrolytic degradation was highly dependent on the hydrophilicity and permeability. ...
Poly(1,8-octanediol citrate) (POC) is a recently developed biodegradable crosslinked elastomer that possesses good cytocompatibility and matchable mechanical properties to soft tissues. However, the thermosetting characteristic reveals a big challenge to manufacture its porous scaffold. Herein, POC elastomer was electrospun into fiber mat using poly(L-lactic acid) (PLLA) as a spinnable carrier. The obtained POC/PLLA fiber mats were characterized by scanning electron microscopy (SEM), dynamic mechanical analysis (DMA), uniaxial tensile test, static-water-contact-angle, thermal analysis, in vitro degradation and biocompatibility test. It was found that the fibrous structure could be formed so long as the POC pre-polymer’s content was no more than 50 wt%. The presence of elastic POC component not only strengthened the fiber mats but also toughened the fiber mats. The hydrophilicity of 50/50 fiber mat significantly improved. In vitro degradation rate of POC based fiber mats was much faster than that of pure PLLA. Cyto- and histo-compatibility tests confirmed that the POC/PLLA fiber mats had good biocompatibility for potential applications in soft tissue engineering.
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... Besides, other environment factors including the addition of drug [140][141][142][143], sterilization [144][145][146][147] and enzymes [148][149][150][151][152][153][154][155][156][157] and so on are reviewed by Alexis [121] and a lot of these facts presented controversial results in so far. ...
Aliphatic biodegradable polyesters have been the most widely used synthetic polymers for developing biodegradable devices as alternatives for the currently used permanent medical devices. The performances during biodegradation process play crucial roles for final realization of their functions. Because physiological and biochemical environment in vivo significantly affects biodegradation process, large numbers of studies on effects of mechanical loads on the degradation of aliphatic biodegradable polyesters have been launched during last decades. In this review article, we discussed the mechanism of biodegradation and several different mechanical loads that have been reported to affect the biodegradation process. Other physiological and biochemical factors related to mechanical loads were also discussed. The mechanical load could change the conformational strain energy and morphology to weaken the stability of the polymer. Besides, the load and pattern could accelerate the loss of intrinsic mechanical properties of polymers. This indicated that investigations into effects of mechanical loads on the degradation should be indispensable. More combination condition of mechanical loads and multiple factors should be considered in order to keep the degradation rate controllable and evaluate the degradation process in vivo accurately. Only then can the degradable devise achieve the desired effects and further expand the special applications of aliphatic biodegradable polyesters.
... Whereas the degradation time of (D, L)PLA is less than PLLA. The degradation rate of PLA also varies with varying pH value [61]. PLA is copolymerized with other polymers to get the better mechanical and physical properties than homopolymer. ...
A stent is a medical device designed to serve as a temporary or permanent internal scaffold to maintain or increase the lumen of a body conduit. The researchers and engineers diverted to investigate biodegradable materials due to the limitation of metallic materials in stent application such as stent restenosis which requires prolonged anti platelet therapy, often result in smaller lumen after implantation and obstruct re-stenting treatments. Biomedical implants with temporary function for the vascular intervention are extensively studied in recent years. The rationale for biodegradable stent is to provide the support for the vessel in predicted period of time and then degrading into biocompatible constituent. The degradation of stent makes the re-stenting possible after several months and also ameliorates the vessel wall quality. The present article focuses on the biodegradable materials for the cardiovascular stent. The objective of this review is to describe the possible biodegradable materials for stent and their properties such as design criteria, degradation behavior, drawbacks and advantages with their recent clinical and preclinical trials.
... PLGA is promoted to improve bone remodeling through absorption and degradation, however, results have shown incomplete remodeling and that the resorption is not osteoinductive. (40,41). Park et al studied the effectiveness of resorbable fixation device in the treatment of zygomaticomaxillary fractures and found complication rates of 7% with resorbable skeletal fixation systems and 4% with metal plate-and-screw systems. ...
Background:
Resorbable osteosynthesis systems are used to treat craniofacial fractures. However, conventional synthetic polyester materials are potentially associated with inflammatory reaction and negative host response and may result in incomplete bone remodeling. The authors have developed a resorbable silk fibroin-based osteosynthesis system and propose that silk screws loaded with bone morphogenetic protein-2 (BMP-2) may exhibit biocompatibility and promote bone remodeling.
Methods:
Resorbable silk screws were prepared and loaded with BMP-2. The BMP-2-loaded and nonloaded silk screws were inserted into the distal femora in 15 Sprague-Dawley rats by self-tapping, similar to conventional metal systems. Animals were euthanized after 1, 3, and 6 months. The femora were explanted at the designated time points, dissected for histologic evaluation, and compared regarding osteoid formation and inflammatory response.
Results:
Increasing organization of newly formed bone tissue was observed over time in both groups. No appreciable difference in inflammation was noted between the BMP-2-loaded and nonloaded silk screws. Notably, mineralized collagen around the periphery of the screw appears to be greatest and more organized in the BMP-2-loaded samples. There was greater recruitment of osteoclasts and osteoblasts around the perimeter of the BMP-2-loaded screws at 3 and 6 months.
Conclusions:
The BMP-2-loaded silk-based fixation device in this study exhibited characteristics comparable to the current nonloaded silk screws with regard to integration and biocompatibility. However, functionalization of silk screws with BMP-2 appeared to allow for more organized collagen and osteoid deposition after 3 and 6 months and may increase the potential of successful remodeling.
... This increase during degradation has been frequently discussed in the literature [13], with most authors suggesting that it results from a rearrangement of the shorter chains generated by the degradation process itself, along with the consequent formation of new crystals. Li et al. [14] and Leenslangl et al. [15] explained this process by the hydrolysis of ester bonds occurring in the amorphous region of the aliphatic polymer, which would explain the observed increase in crystallinity. They posited that degradation proceeds in two main stages. ...
Magnetic composite scaffolds of polycaprolactone/Fe doped nanohydroxyapatite (PCL/nFeHA) with different composition ratios have been fabricated lyophilization for the purpose of bone-tissue engineering. Magnetic measurements reveal some interaction between the Fe particles that decreases steadily as the nFeHA is diluted in the polymer. All the scaffolds were characterized before and after in vitro degradation for over 28 weeks. The nFeHA nanoparticles decreased the initiation rate of hydrolytic degradation. After 16 weeks degradation, thermograms of the first heating revealed two melting peaks, which could be attributed to the presence of crystals of two different sizes. GPC results indicated that Mw and Mn were unaffected by the degradation with no cleavage of the macromolecular chains.
... However, the idea of incorporating small amounts of short degradable units into the PU backbone [51] was the stimulus and motivation for the present study. As the lactide-based derivatives are efficient degradable materials [39,51,52,53], we prepared an oligomeric D,L-lactide-based diol (DLL) containing, on average, two lactide units in the chain [45]. The conditions of the preparation and multi-scale characterization of the four-component PU films (containing, in addition to macrodiol, diisocyanate, chain extender and oligomeric DLL diol in the PU backbone) have been recently published [45,46]. ...
... However, the idea of incorporating small amounts of short degradable units into the PU backbone [51] was the stimulus and motivation for the present study. As the lactide-based derivatives are efficient degradable materials [39,51,52,53], we prepared an oligomeric D,L-lactide-based diol (DLL) containing, on average, two lactide units in the chain [45]. The conditions of the preparation and multi-scale characterization of the fourcomponent PU films (containing, in addition to macrodiol, diisocyanate, chain extender and oligomeric DLL diol in the PU backbone) have been recently published [45,46]. ...
... However, the idea of incorporating small amounts of short degradable units into the PU backbone [51] was the stimulus and motivation for the present study. As the lactide-based derivatives are efficient degradable materials [39,51,52,53], we prepared an oligomeric D,L-lactide-based diol (DLL) containing, on average, two lactide units in the chain [45]. The conditions of the preparation and multi-scale characterization of the fourcomponent PU films (containing, in addition to macrodiol, diisocyanate, chain extender and oligomeric DLL diol in the PU backbone) have been recently published [45,46]. ...
The extent of the hydrolytic degradation of aliphatic polyurethane (PU) films made from polycarbonate-based aliphatic macrodiol (MD), diisocyanate-1,6-hexane, butane-1,4-diol (BD) and D,L-lactide-based oligomeric diol (DLL) was tested in phosphate-buffered saline (PBS) for a period of up to 12 months. Two macrodiols of equal molecular weight (∼2000 Da), differing in chain composition and regularity, and equal MD-to-BD-to-DLL molar ratios were chosen for the PU synthesis. The isocyanate-to-total hydroxyl group ratio was kept constant at 1.05. The functional properties of raw four-component polyurethane films and samples immersed for 1, 3, 6, 9 and 12 months in a model physiological environment (37 °C, pH = 7.4) were studied from the segmental up to the macroscopic level. Tensile testing and water uptake experiments, as well as DSC, SEM, AFM, FTIR and WAXD analyses, were used for the comprehensive characterization of the raw and PBS-treated films. The study shows that the untreated four-component PU films are highly elastomeric materials with very high tensile strength and suitable thermal properties for potential medical coating/film applications. The DLL oligomeric diol turned out to be a very efficiently degradable unit, leading to substantial mechanical property deterioration. The products of more regular macrodiol have higher tendency to the degradation process; 89 % or 94 % of the original toughness value is lost in just 12 months of immersion. The studied type of PU can be practically used either as fairly stable high-performance elastomers for short-term applications (up to 3 months) or as degradable materials, when the time of exposure to the physiology-mimicking conditions is sufficient.
... The block copolymers have the capability of self assembly into intermittent geometry with long-range order and contain at least two distinct polymer chains, covalently bound at one point. The copolymers have the ability to control their amphiphilic behavior, mechanical and physical properties by adjusting the ratio of the constituting blocks or adding new blocks of desired properties (Leenslag et al. 1987). The brisk development of block copolymers towards the drug delivery formulations is due to the versatile and flexible structural design. ...
The amphiphilic block copolymers are composed of various combinations of hydrophilic and hydrophobic block unimers. The variation in unimer ratio alters the surface as well as micelle-forming properties of the block copolymers. These nanoscopic micelles have the ability to encapsulate hydrophobic compounds and act as potential drug carrier. MePEG-PCL copolymers with various block lengths were synthesized by ring-opening polymerization and characterized by (1)HNMR, GPC, WXRD and DSC. The number average molecular weight of the block copolymer was found to vary from 7511 to 21,270 as determined by GPC and (1)HNMR studies. The surface topology of the polymer films was determined by AFM analysis, which shows a smoother surface with increased MePEG contents in the block copolymers. The protein-binding assay indicates a better biocompatibility of the block copolymers in comparison to MePEG or PCL alone. The CMC of the block copolymer provides the information about micelle formations for encapsulation of hydrophobic materials and affects the in vitro release.
... AD in the time of Galen, who treated wounded gladiators. The idea of using polyglycolic acid suture material for fracture fi xation plates and screws was patented in 1973. [1] The interest in the use of bioresorbable materials for internal fi xation of fractured bones instead of traditionally applied metallic devices has been increasing since 1965. [2] The use of polylactic acids (PLA) for the development of surgical implants started in 1966. [3] In 1966, it was reasoned that polylactic acid would be useful for degradable surgical implants. [1] The stabilization of mandibular fractures in dogs with PLA osteosynthesis plates and screws was reported for the fi rst time in 1972. Since 19 ...
The influence of mild CO2 treatment on thermal properties of poly (l-lactic) acid (PLLA) is discussed in this article. A slowly crystallizing PLLA with 4% d-isomer was treated with CO2 at room temperature and moderate pressures (up to 6.0 MPa) for short times, not longer than 20 minutes. These mild treatments are sufficient to develop ε-form (PLLA/CO2 complex), which evolves to α"-mesophase after desorption of CO2. The amount of mesophase depends on the pressure of CO2 and the sorption times, and significantly affects the thermal properties of PLLA. Although the mesophase melts immediately above the glass transition, it affects subsequent cold crystallization. The influence of CO2 sorption time and pressure on the cold crystallization kinetics of PLLA is quantified here, and it is found that only a few minutes of treatment with low-pressure CO2 is sufficient to enhance the crystallization rate. After longer exposure to CO2, α-crystals also develop, especially under high CO2 pressure, hence proper adjustment of these parameters can allow tuning the structure and thermal properties of PLLA. The results demonstrate the possibility of producing CO2-induced mesophase at room temperature using very short sorption times, thus introducing a fast, green and cost-effective way to tailor the crystallization kinetics of PLLA.
Poly(lactic acid) (PLA), one of the aliphatic polyesters, is susceptible to hydrolytic degradation, in contrast to aromatic polyesters such as poly(ethylene terephthalate). The hydrolytic degradation rate of PLA should be manipulated when PLA‐based materials are used for biomedical, pharmaceutical, and environmental applications. During the course of hydrolytic degradation, low‐molecular‐weight water‐soluble oligomers and monomers are formed by the cleavage of chains and are released from the mother materials, resulting in weight loss. The chains in the crystalline regions are more hydrolysis resistant compared with those in the amorphous regions because the access of water molecules to the chains inside the rigid crystalline regions is prohibited. The material parameters include molecular and highly ordered structures, additives including other polymers and fibers, and the material morphology. Hydrolytic degradation causes the cleavage of ester groups, resulting in an increased number of hydrophilic terminal groups.
The exceptional properties of mesoporous silica nanoparticles (MSNs) promote facile functionalization for improved drug delivery in nanotechnology. Recent advancements in this field have experienced the potential applications of MSNs and porous silicon (PSi). Tunable pore size, large surface area, and better surface properties make the materials possible to hold large amounts of payloads and prevent premature degradation. In this chapter, we will focus on and discuss the main route of preparation and applications of MSNs and silica nanomaterials.
The chapter is based on the insights related to the scale-up, preclinical and clinical status of Poly (Lactide-Co-Glycolide), and its copolymers-based drug delivery systems.
Study Design
Pediatric mandible fractures mandate special consideration because of unerupted teeth, mixed dentition, facial growth and the inability to tolerate maxillomandibular fixation. No consensus exists as to whether resorbable or titanium plating systems are superior with regards to clinical outcomes.
Objective
This study aims to systematically review and compare the outcomes of both material types in the treatment of pediatric mandible fractures.
Methods
After PROSPERO registration, studies from 1990-2020 publishing on outcomes of ORIF of pediatric mandible fractures were systematically reviewed according to PRISMA guidelines. An additional retrospective review was conducted at a pediatric level 1 trauma center.
Results
1,144 patients met inclusion criteria (30.5% resorbable vs. 69.5% titanium). Total complication rate was 13%, and 10% required a second, unplanned operation. Complication rates in the titanium and resorbable groups were not significantly different (14% vs. 10%; P = 0.07), and titanium hardware was more frequently removed on an elective basis (P < 0.001). Condylar/sub-condylar fractures were more often treated with resorbable hardware (P = 0.01); whereas angle fractures were more often treated with titanium hardware (P < 0.001). Within both cohorts, fracture type did not increase the risk of complications, and comparison between groups by anatomic level did not demonstrate any significant difference in complications.
Conclusions
Pediatric mandible fractures requiring ORIF are rare, and hardware-specific outcomes data is scarce. This study suggests that titanium and resorbable plating systems are equally safe, but titanium hardware often requires surgical removal. Surgical approach should be tailored by fracture anatomy, age-related concerns and surgeon preference.
Poly(lactic acid) (PLA) is a biodegradable polymer material used for the fabrication of objects by fused filament fabrication (FFF) 3D printing. FFF 3D printing technology has been quickly spreading over the past few years. An FFF-3D-printed object is formed from melted polymer extruded from a nozzle layer-by-layer. The mechanical properties of the object, and the changes in those properties as the object degrades, differ from the properties and changes observed in bulk objects. In this study we evaluated FFF-3D-printed objects by uniaxial tensile tests and four-point flexural tests to characterize the changes of three mechanical properties, namely, the maximum stress, elastic modulus, and breaking energy. Eight types of test pieces printed directly by an FFF 3D printer using two scan patterns and two interior fill percentages (IFPs) were tested by the aforesaid methods. The test pieces were immersed in saline and kept in an incubator at 37 °C for 30, 60, or 90 days before the mechanical testing. The changes in the mechanical properties differed largely between the test piece types. In some of the test pieces, transient increases in strength were observed before the immersion degraded the strength. Several of the test piece types were found to have superior specific strength in the tests. The results obtained in this research will be helpful for the design of PLA structures fabricated by FFF 3D printing.
This chapter outlines the main stem cell lines and nanomaterials utilized in tissue engineering for regenerative medicine, with a distinct focus on the cardiovascular system, which is our research area of interest.
With the increase in the risk from sports and aging there has been a large increase in fracture and other bone related problems. Over the last decade, the use of bone graft substitutes in bone tissue engineering has dramatically increased. A large number of materials have been used including injectable cements to composite porous solids and from metals to polymers composites. The natural biopolymers such as chitosan and polyaminosaccharide widely take part as bone substitute, having the properties like biocompatibility, antiinflammatory, antimicrobial activity, biodegradability and nontoxicity, immunogenicity, controlled release behavior, mucoadhesive nature, and economic feasibility. In addition, chitosan carries structural properties that readily undergo modification via physical or chemical processes. This chapter overviews the use of chitosan as resorbable bone graft in tissue engineering and also slightly emphasizes the use of synthetic polymers as a bone graft.
This article reports on the histologic findings from a larger study that was designed to investigate whether the attachment of scar tissue to underlying bone, which is normally found after palatal surgery, can be prevented by using biodegradable poly-(L-lactic) acid membranes. Von Langenbeck's procedure was simulated in 12-week-old beagle dogs without clefts. In one group normal wound healing was allowed. In two groups, membranes were inserted immediately after surgery or 3 weeks thereafter. Sham and control groups were also included. Histologic evaluation was carried out at regular intervals. Reports have been published on other aspects, such as clinical wound healing, contraction and maxillary arch development in beagle dogs following this treatment. After direct implantation of membranes, wound healing was retarded. Disintegration of the membranes started soon after implantation and remaining particles were surrounded by a fibroblastic sheath and a fibrous capsule. At sites where membrane particles persisted, attachment of the scar tissue to the underlying bone by Sharpey's fibers was prevented.
In earlier chapters, the potential (and associated issues) of nanoparticles in influencing mechanical and thermal properties of polymers is discussed. To further exploit their functionality and achieve combinatorial properties, ‘tailoring’ or ‘tuning’ holds the key. In this chapter, some of the important functional properties of these materials will be briefly reviewed in order to understand the advantages and disadvantages of considering multi-functionality.
Background: Through a full investigation of biodegradable scaffolds, we propose a new self-expanding degradable poly-L-lactide coated endotracheal stent based on the design, production, experimental and clinical applications of nickel titanium memory alloy stent. Objective: To design a kind of biodegradable endotracheal stent with poly-L-lactide and hydroxyapatite, and to test its mechanical properties, biocompatibility and biodegradation capacity. Methods: With the technology of computer aided design, the stents were prepared with poly-L-lactide (Mr 150 000) and hydroxyapatite materials, 20 mm to 26 mm in diameter. The mechanical properties were tested using a universal testing machine. These poly-L-lactide/hydroxyapatite stents were implanted into dog models of tracheal stenosis at an appropriate size. The histopathological changes of the tracheas were observed, and biodegradation property was studied via molecular weight changes and weight loss ratio after 4, 8, 12, 16 weeks. Results and conclusion: The average radial supporting force of the tracheal stent was 7.8 kPa, the percentage of stent surface coverage was less than 20%, the stent expansion rate was ≥ 4%, and the stent longitudinal shortening rate was ≤ 9%, which reached the mechanical requirements for degradable endotracheal stents. After 4-16 weeks, there was no significant inflammatory response. The decline in molecular weight changes and weight loss ratio was higher for in vivo degradation than in vitro degradation at different time (P < 0.05). These findings indicate that poly-L-lactide/hydroxyapatite composite stents have good mechanical properties, biocompatibility and biodegradability.
Synthetic biodegradable polymers are widely used in medicine and biology and are essential components of drug delivery vehicles, tissue engineering scaffolds, and biomedical devices. There is, therefore, great interest in designing new synthetic biodegradable polymers for biomedical applications. A key property that controls the function and effectiveness of biomedical polymers is their rate of degradation. In this review article, we will describe the physical and chemical mechanisms by which the major classes of biomedical polymers degrade. In particular, the hydrolysis of polyesters, polyanhydrides, polyorthoesters, and polyketals is discussed. The hydrolysis of these polymers by water is described, and the factors that influence their water hydrolysis rates are also discussed, such as catalysis of hydrolysis by acid, base, and enzymes. In addition, the physical factors that influence polymer hydrolysis rates will also be described, such as polymer crystallinity and hydrophobicity. We anticipate that this information will provide the basis for predicting the hydrolysis kinetics of synthetic polymers and will assist in the design of new polymers for biomedical applications.
We evaluated the mechanical properties of biodegradable microstructures produced by a three-dimensional microfabrication system that we had developed. Biodegradable materials are indispensable in developing modern medical equipment, but the lack of a suitable processing method is hindering the application of these materials. Our fabrication system has achieved a high resolution (50μm) and the high bio-applicability of the fabricated structure has been verified bycultivating cell lines in a biodegradable vessel fabricated using our system. However, the mechanical strength of the fabricated structure had been unknown. To measure the mechanical strength of our structures, we fabricated test pieces using Poly (D, L-lactide-co-glycolide), and subjected them to a tensile test. In order to evaluate the mechanical strength of the structures, two types of test piece were prepared, one scanned parallel to the tensile direction, and the other scanned perpendicular to it. The strength of our fabricated ructure was shown to be about 55 percent of the tensile strength of structures made from the same material but fabricated using the conventional method. Our fabrication system is expected to find applications in tissue engineering in the near future.
Organ or tissue failure remains a frequent, costly, and serious problem in health care despite advances in medical technology. The large number of patients suffering from tissue losses or organ failures is demonstrated by the approximately 8 million surgical procedures and 40 to 90 million hospital days required annually to treat these problems (Langer and Vacanti, 1993). Available treatments now include transplantation of organs from one individual to another, performing surgical reconstruction, use of mechanical devices (e.g., kidney dialyzer), and drug therapy. However, these treatments are not perfect solutions. Transplantation of organs is limited by the lack of organ donors, possible rejection, and other complications. For example, there are only 3000 donors available in contrast to 30,000 patients who die from liver failure each year (American Liver Foundation, 1988). Mechanical devices cannot perform all functions of an organ, e.g., kidney dialysis can only help remove some metabolic wastes from the body. Likewise, drugs can only replace limited biochemical functions of an organ or tissue, and physiologic control of drug levels comparable to the control systems of the body is difficult to achieve. For example, although diabetes can be partially treated by administration of insulin, it is still the leading cause of chronic renal failure and blindness (Chukwuma, 1995; Hoelscher et al, 1995; Sander and Wilson, 1993). This is partly due to difficulties in controlling the drug level in vivo (Levesque et al, 1992). Financially, the cost of surgical procedures is very high ($150,000 for a liver transplant). It is estimated that almost half of the United States $800 billion in annual health care costs are due to loss or malfunction of tissue or organs (Langer and Vacanti, 1993).
To study the effect of membrane morphology variation on biodegradation and the behavior of adhering cells, three types of poly(L-lactic acid) (PLLA) membranes with different morphologies-particulate, porous, and dense-were prepared. Degradation of the PLLA membranes was performed at 37°C in hydrogen peroxide solution to accelerate degradation. In addition, these degradation curves were compared with degradation in PBS solution. The estimations of degradation in the two solutions were analyzed by gel permeation chromatography, scanning electron microscopy, and differential scanning calorimetry for 12 and 24 weeks. In addition, cell behavior on the three types of PLLA membrane was also investigated. The results showed that the molecular weight of PLLA membranes dropped gradually during the in vitro degradation period in both hydrogen peroxide and PBS solutions. The surface morphologies of the three types of membrane were observed to differ in the accelerated degradation system, suggesting that morphology affected the crystallinity and resulted in different degradation rates. Adhering cell behavior was also affected by surface morphology, with cells on the particulate membrane displaying the best viability. As the degradation rate of the particulate membrane was the slowest and its biocompatibility was the best, the particulate PLLA membrane may be most suitable for long-term orthopedic implants.
The effect of high energy ball milling, HEBM, and the presence of kaolin on the structure, morphology, and biofilm development of polylactic acid, PLA, were studied. Biofilm development was evaluated in terms of structural and/or morphological variations so as the sole presence of kaolin. Composites based on PLA filled with kaolin were prepared by HEBM followed by hot pressing to obtain films. Structure was studied by X-ray diffraction and Fourier transformed infrared spectroscopy whereas morphology was inspected by scanning electron microscopy and atomic force microscopy. To study biofilm development on the surface of these materials, Pseudomonas fluorescens B52 were used. The shear forces from the milling process favor kaolin dispersion within the PLA. Longer milling times and cryogenic conditions improve clay dispersion. Subsequent hot pressing process enhances the most ordered structure of PLA (α-phase) which is also favored with previous milling at longer times and under cryogenic conditions. Changes in P. fluorescens biofilm development are mainly due to modifications of surface properties induced by structural variations, being the most ordered structures those which better support bacterial adhesion and proliferation. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42676.
The development of porous materials for use as scaffolds for the sustained 3D growth of tissue is a fast growing area in TE that has attracted commercial interest to a large extent. To fabricate both polymer scaffold and composite scaffold, many techniques are available. By using proper technique, the porous structure of polymeric and composite scaffolds could be controlled by varying the processing or formulation parameters. It is often necessary to modify the surface properties of biomaterials without changing the bulk attributes as a biomaterial rarely possess good surface characteristics suitable for bone tissue engineering. This chapter reviews the various existing methodologies to fabricate scaffolds and to modify the surface properties of scaffolds. It also discusses the study of interactions between tissues and biomaterials.
In this work, highly electrically and thermally conductive biopolymer composites were prepared by low-temperature expandable graphite (EG) filling Poly(L-lactic acid) (PLLA) via an in situ exfoliation melt blending process. The electrical conductivity of the composites with various graphite contents was measured by a four-point probe resistivity determiner and a high value of 0.37 S/cm was obtained at 70 wt.% EG content. A hot-disk method was used to evaluate the thermal conductivity of the composites. At EG loading fraction of 70%, thermal conductivity of PLLA/EG composites reached to the highest 26.87 W/mK, which is 100 times higher than neat PLLA. The electrical percolation was observed in the vicinity of the thermal percolation threshold concentration. The expansion of EG was crucial to the overall conductivity of the blends, which was confirmed by X-ray diffraction (XRD) analysis and scanning electron microscope (SEM). Dynamic rheology analysis was applied to study the structural change by the interconnection of the exfoliated graphite flakes and the formation of the networks in the blends. Thermogravimetric analysis (TGA) was employed to determine the thermal properties of the investigated PLLA/EG composites.
Poly(lactic acid) (PLA) is a bio-based biodegradable polymer that can be produced from renewable resources including starch from corn and potatoes, sugar from beets and sugar cane, and so forth. The carbon in PLA originates from atmospheric carbon dioxide, which is immobilized in glucose by photosynthesis; therefore, the carbon dioxide formed by its disposal, incineration, or biodegradation does not increase the total amount of atmospheric carbon dioxide. Poly(lactic acid) and its copolymers have attracted significant attention in environmental, biomedical, and pharmaceutical applications and as alternatives to petro-based polymers. Among their applications as alternatives to petro-based polymers, packing applications are the primary one. Most commercially available poly(L-lactic acid) (PLLA) is used for packaging, automobile interiors, electronics chassis and other consumer products. However, some applications require a higher mechanical performance and resistance to hydrolytic/thermal degradation. In addition to composite or fiber-reinforced plastic formation, stereocomplexation between enantiomeric PLLA and poly(D-lactic acid) is a promising method for producing high-performance PLA-based materials because it has been shown to enhance the mechanical performance and resistance to hydrolytic/thermal degradation of PLA-based materials. The physical properties, hydrolytic degradation, and biodegradation of PLA can be controlled by altering, for instance, their molecular and higher ordered structures. This chapter outlines the basic aspects of synthesis, processing, structures, physical properties, degradation and applications of PLA.
Mathematical models of controlled release that span the in vitro to in vivo transition are needed to speed the development and translation of clinically-relevant controlled release drug delivery systems. Fully mechanistic approaches are often challenged due to the use of highly-parameterized mathematically complex structures to capture the release mechanism. The simultaneous scarcity of in vivo data to inform these models and parameters leads to a situation where overfitting to capture observed phenomena is common. A data-driven approach to model development for controlled drug release from polymeric microspheres is taken herein, where physiological mechanisms impacting controlled release are incorporated to capture observed changes between in vitro release profiles and in vivo device dynamics. The model is generalizable, using non-specific binding to capture drug-polymer interactions via charge and molecular structure, and it has the ability to describe both inhibited (slowed) and accelerated release resulting from electrostatic or steric interactions. Reactive oxygen species (ROS)-induced degradation of biodegradable polymers was incorporated via a reaction-diffusion formalism, and this suggests that ROS may be the primary effector of the oft-observed accelerated in vivo release of polymeric drug delivery systems. Model performance is assessed through comparisons between model predictions and controlled release of several drugs from various-sized microparticles in vitro and in vivo.
Copyright © 2015. Published by Elsevier B.V.
Copolymers of (R)-3-hydroxybutyrate (3HB) and (R)-lactate ((R)-2-hydroxypropionate: 2HP) units were synthesized by polycondensation reaction from methyl esters of 3HB and 2HP in the presence of titanium-based catalyst. Mixing of two monomers from the beginning of polymerization yielded random copolymers of 3HB and 2HP units. On the other hand, by controlling the time of mixing of two monomers, copolymers with blocking tendency were obtained. The structure and thermal properties of the obtained copolymers were characterized by H-1 and C-13 NMR, X-ray diffraction, differential scanning calorimetry, and optical microscopy. Glass-transition temperature of the copolymers was mainly governed by the copolymer composition, and the values varied linearly with the composition. In contrast, the melting temperature was strongly depending on the sequential length of crystallizable monomeric unit, and the values were in inverse proportion to the number-averaged sequential length of crystallizable monomeric unit. The crystallinity of the copolymer samples was affected by both the composition and sequential length of crystallizable monomeric unit. The finding is valuable for design of copolymer molecules with desirable thermal properties by controlling both the copolymer composition and sequential structure.
A series of nominally stable polymers, including polyamides, polyesters and polyurethanes, have been synthesised with the incorporation of a **1**4C-label. These polymers have been subjected to a variety of enzymes in vitro and their degradation monitored by the release of **1**4C. The results show that this degradation is frequently associated with the presence of enzymes such as trypsin, chymotrypsin, papain and esterase. Although the amounts of degradation observed are small, these observations suggest that many polymers may be susceptible to surface degradation in vivo.
Finite element models (using beam elements) were used to simulate plated intact bone remodeling (subsequent to fracture healing) beneath internal fixation plates of variable stiffness. Initially, a series of two-dimensional human femur models without fracture simulation were developed. Parametric studies of the effects of reduced plate stiffness indicated that plates with only the axial stiffness reduced permit significant bone stress increases whereas reduction in plate bending stiffness does not increase bone stress. Elevation of plated bone stress should help to deter the occurrence of osteoporosis, particularly in the plated side of the bone. Plates with differing structural and material characteristics were modeled and Ti-6A1-4V plates with thinned or I-beam cross sections were found to be possible prototypes which allow higher bone stresses than relatively rigid standard Vitallium plates. Simulation of bone remodeling beneath various plates via changes in bone cross section in the finite element models revealed that thinning of the bone cortex directly beneath the plate is likely to occur in order to increase plated bone stress. However, cortical thinning beneath very rigid plated models did not increase plated bone stress, implying that more osteoporosis should occur beneath such plates (as has been observed experimentally).
Internal fixation devices of less bending stiffness than conventional plates made of stainless steel or vitallium were compared with conventional plates in a study of fracture healing. The material for this investigation was a fine graphite fiber reinforced methyl methacrylate resin composite with a modulus of elasticity approximately ten times less than that of stainless steel. Osteotomies were performed on canine radii. Internal fixation was accomplished by means of a composite plate on the left side, and a stainless steel plate on the right. Clinical assessment, as well as biomechanical and quantitative histological techniques, were used to compare osteotomy healing of the two sides. At four months, all osteotomies had healed and the bioengineering tests showed radii from the two sides had equivalent strength. However, significantly less cortical porosity was found in the side with the composite plate (6.8 per cent), as compared to that of the stainless steel plated side (14 per cent). These results suggest that a less stiff fixation plate may have some advantage in the treatment of long bone fracture if there is no implant failure, and if union rates are equivalent.
Poly(L-lactide) (PLLA) with an extremely high molecular weight (Mv up to 1 X 10(6)) was synthesized at a low catalyst concentration (0.015 wt%) and temperatures between 100-110 degrees C. Besides good mechanical properties the as-polymerized PLLA exhibited a microporous structure. Plates and screws of this material were used for the treatment of mandibular fractures, both in dogs and in sheep. Bone healing was uneventful and proceeded without callus formation or signs of inflammation. Fracture healing was accompanied by a progressive degradation of the microporous implants of PLLA.
