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Synthesis of polyethylene glycol-trimethylene carbonate (PEG(TMC x ) 2 ) oligomers and their corresponding isocyanate-terminated adhesives.
Source publication
Purpose:
Intervertebral disk degeneration is the main cause of chronic back pain. Disk degeneration often leads to tearing of the annulus fibrosus (AF) and extrusion of the nucleus pulposus (NP), which compresses the nerves. Current treatment involves removing the herniated NP and suturing the damaged AF tissue. This surgical approach has several...
Contexts in source publication
Context 1
... PEG-PTMC triblock copolymers were syn- thesized by ring-opening polymerization of TMC with PEG as the initiator, as shown in Figure 1. In a typical procedure TMC, PEG 1k and Sn(Oct) 2 (0.2 mmol/per mol monomer) as catalyst were reacted in the melt at 150 o C for 3 hours in an inert argon atmosphere. ...
Context 2
... PEG-PTMC triblock copolymeric oligomers were then end-functionalized by reaction with 1,4-di- isocyanatobutane (BDI) as depicted in Figure 1. A weighed quantity of the oligomer was charged under nitrogen into a 3-neck flask. ...
Context 3
... subsequent functionalization with butane diiso- cyanate, FTIR analysis demonstrated the presence of urethane bonds and free isocyanate groups. In Figure 4 the FTIR spectra of PEG-(TMC 4 ) 2 and the corresponding NCO functionalized compound (see Fig. 1 for the reac- tion scheme) are presented. Characteristic absorption peaks can be identified at 3,500 cm −1 (O-H stretching), 2,850-2,994 cm −1 (C-H stretching) and at 1,450 cm −1 (C-H bending). The peaks at 1,707-1,770 cm −1 are due to the carbonyl groups of TMC units. In the correspond- ing diisocyanate-terminated oligomer, 2 ...
Citations
... Polytrimethylene carbonate material is generating interest to fabricate space-fillers for AF defects [92,94,132]. Long et al. [92] developed a composite repair strategy that combines a conical space-filler composed of polytrimethylene carbonate secured in place by fibrin-genipin adhesive sealant, previously tuned to match the shear properties of native AF tissue [130]. ...
Background: Intervertebral disc degeneration has an annual worldwide socioeconomic impact masked as low back pain of over 70 billion euros. This disease has a high prevalence over the working age class, which raises the socioeconomic impact over the years. Acute physical trauma or prolonged intervertebral disc mistreatment triggers a biochemical negative tendency of catabolic-anabolic balance that progress to a chronic degeneration disease. Current biomedical treatments are not only ineffective in the long-run, but can also cause degeneration to spread to adjacent intervertebral discs. Regenerative strategies are desperately needed in the clinics, such as: minimal invasive nucleus pulposus or annulus fibrosus treatments, total disc replacement, and cartilaginous endplates decalcification.
Main body: Herein, it is reviewed the state-of-the-art of intervertebral disc regeneration strategies from the perspective of cells, scaffolds, or constructs, including both popular and unique tissue engineering approaches. The premises for cell type and origin selection or even absence of cells is being explored. Choice of several raw materials and scaffold fabrication methods are evaluated. Extensive studies have been developed for fully regeneration of the annulus fibrosus and nucleus pulposus, together or separately, with a long set of different rationales already reported. Recent works show promising biomaterials and processing methods applied to intervertebral disc substitutive or regenerative strategies. Facing the abundance of studies presented in the literature aiming intervertebral disc regeneration it is interesting to observe how cartilaginous endplates have been extensively neglected, being this a major source of nutrients and water supply for the whole disc.
Conclusion: Several innovative avenues for tackling intervertebral disc degeneration are being reported – from acellular to cellular approaches, but the cartilaginous endplates regeneration strategies remain unaddressed. Interestingly, patient specific approaches show great promise in respecting patient anatomy and thus allow quicker translation to the clinics in the near future.
... FibGen involved a genipin-crosslinked fibrin gel with a formulation previously tuned to match the shear properties of the native AF tissue [20]. The space filling PTMC scaffolds consisted of 5,000g/mol oligomers crosslinked with stereolithography to ensure a precise structure that mimicked the complex architecture of the AF collagen bundles which are oriented in an angle-ply fashion that evolve from ±30° in the inner AF to ±45° in the outer AF [21]. Two scaffold geometries were evaluated: a truncated cone shape and a cylindrical shape. ...
Statement of significance:
Lower back pain is the leading cause of global disability and commonly caused by defects and failure of intervertebral disk tissues resulting in herniation and compression of adjacent nerves. Annulus fibrosus repair materials and techniques have not been successful due to the challenging mechanical and chemical microenvironment and the needs to restore biomechanical behaviors and promote healing with negligible herniation risk while being delivered during surgical procedures. This work addressed this challenging biomaterial and clinical problem using novel materials including an adhesive hydrogel, a scaffold capable of cell delivery, and a membrane to prevent herniation. Composite repair strategies were evaluated and optimized in quantitative three-part study that rigorously evaluated disk repair and provided a framework for evaluating alternate repair techniques.
... Many scaffolds, both natural and synthetic, have been used for IVD tissue engineering [26][27][28][29][30][31], but these scaffolds differ from natural IVD in components or structure. We fabricated and characterized a natural-origin, biphasic scaffold derived from 2 types of ECM: an outer BMG phase and inner ACECM phase. ...
Tissue engineering has provided an alternative therapeutic possibility for degenerative disc diseases. However, we lack an ideal scaffold for IVD tissue engineering. The goal of this study is to fabricate a novel biomimetic biphasic scaffold for IVD tissue engineering and evaluate the feasibility of developing tissue-engineered IVD in vitro and in vivo . In present study we developed a novel integrated biphasic IVD scaffold using a simple freeze-drying and cross-linking technique of pig bone matrix gelatin (BMG) for the outer annulus fibrosus (AF) phase and pig acellular cartilage ECM (ACECM) for the inner nucleus pulposus (NP) phase. Histology and SEM results indicated no residual cells remaining in the scaffold that featured an interconnected porous microstructure (pore size of AF and NP phase 401.4 ±13.1 μm and 231.6±57.2 μm, respectively). PKH26-labeled AF and NP cells were seeded into the scaffold and cultured in vitro. SEM confirmed that seeded cells could anchor onto the scaffold. Live/dead staining showed that live cells (green fluorescence) were distributed in the scaffold, with no dead cells (red fluorescence) being found. The cell - scaffold constructs were implanted subcutaneously into nude mice and cultured for 6 weeks in vivo. IVD-like tissue formed in nude mice as confirmed by histology. Cells in hybrid constructs originated from PKH26-labeled cells, as confirmed by in vivo fluorescence imaging system. In conclusion, the study demonstrates the feasibility of developing a tissue-engineered IVD in vivo with a BMG- and ACECM-derived integrated AF-NP biphasic scaffold. As well, PKH26 fluorescent labeling with in vivo fluorescent imaging can be used to track cells and analyse cell - scaffold constructs in vivo.
... Recent efforts toward generating the anatomical shape of fibrocartilaginous tissues most commonly utilize a scaffolding material formed into the native tissue's geometric shape [9][10][11][12][13][14][15]. With regards to matrix anisotropy, electrospinning has been used to align either organic or inorganic fibers as a template for directed tissue growth [16][17][18]. ...
The knee meniscus, intervertebral disc, and temporomandibular joint (TMJ) disc all possess complex geometric shapes and anisotropic matrix organization. While these characteristics are imperative for proper tissue function, they are seldom recapitulated following injury or disease. Thus, this study's objective was to engineer fibrocartilages that capture both gross and molecular structural features of native tissues. Self-assembled TMJ discs were selected as the model system, as the disc exhibits a unique biconcave shape and functional anisotropy. To drive anisotropy, 50:50 co-cultures of meniscus cells and articular chondrocytes were grown in biconcave, TMJ-shaped molds and treated with two exogenous stimuli: biomechanical (BM) stimulation via passive axial compression and bioactive agent (BA) stimulation via chondroitinase-ABC and transforming growth factor-β1. BM + BA synergistically increased Col/WW, Young's modulus, and ultimate tensile strength 5.8-fold, 14.7-fold, and 13.8-fold that of controls, respectively; it also promoted collagen fibril alignment akin to native tissue. Finite element analysis found BM stimulation to create direction-dependent strains within the neotissue, suggesting shape plays an essential role toward driving in vitro anisotropic neotissue development. Methods used in this study offer insight on the ability to achieve physiologic anisotropy in biomaterials through the strategic application of spatial, biomechanical, and biochemical cues.
The advancement in the preparation of biomaterials that possess tissue engineering applications has predominantly concerted on developing biomimetic materials inherited with the properties of designing new tissue and very definite in cellular responses. The tissue generation is owed by identifying specific biomolecules which can be influenced by changing the microenvironment. Tissue engineering scaffolds and drug delivery systems are gaining huge interest these days. However, one of the common threats associated with the insertion of an implant is the colonization of pathogenic microbes and the development of bacterial/fungal or mixed biofilms in the implant. Theoretically, biomimetic materials mimic the functions of extracellular matrix (ECM) in tissues; therefore, biomimetic scaffolds can offer biological signals for cell-matrix interactions to promote tissue growth. Various biodegradable polymers are used as a base for local drug delivery or temporary sustenance for tissue regeneration. These polymers are disintegrated nonenzymatically through hydrolysis or by particular enzymes. Excellent biocompatibility marks them as competent material for various medical purposes. Nevertheless, the renewal of living tissue and the capability to preclude microbial colonization should be considered while fabricating materials for implant construction. This chapter gives insight into the background and applications of biomaterials with antimicrobial properties and the prospects of bioinspired materials.
A fast increasing demand of medical products based on biomaterials and tissue engineering has led to an extensive growth in biomedical research in the past two decades. A highly interesting class of biomaterials are polymer-based composites, which nowadays are widely used in biomedical applications due to their outstanding physical and mechanical properties. In this paper, we aim to summarize the advancement in polymer-based composites with regard to their properties, structure and fabrication using different techniques. Bioactive polymer-based composites, such as bone-forming, electrically conductive, magnetic, bactericidal and oxygen-releasing materials, as well as non-bioactive polymer-based composites containing reinforcing fillers and porogens are discussed. Amongst others, scaffold structures fabricated by particle leaching, electrospinning and additive manufacturing are described. In each section, significant and recent advances of polymer-based composites in biomedical applications are addressed.
Aliphatic polycarbonates have gained increased attention as biomaterials largely owing to their biocompatibility and tunable degradation. Moreover, the ability to introduce functional handles in the polymer backbone through careful design of cyclic carbonate monomers or copolymerization with other biodegradable polymers has significantly contributed to the interest in exploiting this class of materials for biomedical applications. Such investigations have enabled their utility to be expanded to a wide variety of applications in the biomedical field, from drug delivery to tissue regeneration and the design of vascular grafts. Herein, we review the synthesis, degradation, and studies into biomedical applications of aliphatic polycarbonates obtained by ring-opening polymerization of cyclic carbonate monomers (ring sizes between 6 and 8). While all synthetic methods will be covered, particular emphasis will be given to materials that have been exploited for therapeutic applications in vitro and in vivo.
The global market for 3D printing materials has grown exponentially in the last decade. Today, photopolymers claim almost half of the material sales worldwide. The lack of sustainable resins, applicable in vat photopolymerization that can compete with commercial materials, however, limits the widespread adoption of this technology. The development of “green” alternatives is of great importance in order to reduce the environmental impact of additive manufacturing. This paper reviews the recent evolutions in the field of sustainable photopolymers for 3D printing. It highlights the synthesis and application of biobased resin components, such as photocurable monomers and oligomers, as well as reinforcing agents derived from natural resources. In addition, the design of biologically degradable and recyclable thermoset products in vat photopolymerization is discussed. Together, those strategies will promote the accurate and waste‐free production of a new generation of 3D materials for a sustainable plastics economy in the near future.
With the development of technology, tissue engineering (TE) has been widely applied in the medical field. In recent years, due to its accuracy and the demands of solid freeform fabrication in TE, three-dimensional printing, also known as additive manufacturing (AM), has been applied for biological scaffold fabrication in craniofacial and dental regeneration. In this review, we have compared several types of AM techniques and summarized their advantages and limitations. The range of printable materials used in craniofacial and dental tissue includes all the biomaterials. Thus, basic and clinical studies were discussed in this review to present the application of AM techniques in craniofacial and dental tissue and their advances during these years, which might provide information for further AM studies in craniofacial and dental TE.
