Poly(propylene fumarate) (PPF) is a biodegradable polymer that has been investigated extensively over the last three decades. It has led many scientists to synthesize and fabricate a variety of ...PPF-based materials for biomedical applications due to its controllable mechanical properties, tunable degradation and biocompatibility. This review provides a comprehensive overview of the progress made in improving PPF synthesis, resin formulation, crosslinking, device fabrication and post polymerization modification. Further, we highlight the influence of these parameters on biodegradation, biocompatibility, and their use in a number of regenerative medicine applications, especially bone tissue engineering. In particular, the use of 3D printing techniques for the fabrication of PPF-based scaffolds is extensively reviewed. The recent invention of a ring-opening polymerization method affords precise control of PPF molecular mass, molecular mass distribution (ƉM) and viscosity. Low ƉM facilitates time-certain resorption of 3D printed structures. Novel post-polymerization and post-printing functionalization methods have accelerated the expansion of biomedical applications that utilize PPF-based materials. Finally, we shed light on evolving uses of PPF-based materials for orthopedics/bone tissue engineering and other biomedical applications, including its use as a hydrogel for bioprinting.
Display omitted
Additive manufacturing affords the construction of complex scaffolds for tissue engineering, yet the limitation in material choice remains a barrier to clinical translation. Herein, a series of ...poly(propylene fumarate-
-propylene succinate) were synthesized using both one-pot and sequential ring-opening copolymerization reactions. Continuous liquid interface production-based photochemical 3D printing utilizing thiol-ene chemistry was used to fabricate precise structures with improved build time over the traditional poly(propylene fumarate)/diethyl fumarate 3D printing processes. Significantly, the materials do not exhibit a yield point under tension and Young's modulus of the 3D printed products can be tuned by more than 2 orders of magnitude (0.6-110 MPa) using polymer composition and the degree of polymerization. Printed constructs degrade fully under hydrolytic conditions and degradation rates can be tailored using polymer composition, polymer sequence, and resin formulation.
The ring-opening copolymerization of maleic anhydride and propylene oxide, using a functionalized primary alcohol initiator and magnesium 2,6-di-tert-butyl phenoxide as a catalyst, was investigated ...in order to produce high end-group fidelity poly(propylene maleate). Subsequent isomerization of the material into 3D printable poly(propylene fumarate) was utilized to produce thin films and scaffolds possessing groups that can be modified with bioactive groups postpolymerization and postprinting. The surface concentration of these modifiable groups was determined to be 30.0 ± 3.3 pmol·cm–2, and copper-mediated azide–alkyne cycloaddition was used to attach a small molecule dye and cell adhesive GRGDS peptides to the surface as a model system. The films were then studied for cytotoxicity and found to have high cell viability before and after surface modification.
Effective control of pain management has the potential to significantly decrease the need for prescription opioids following a surgical procedure. While extended release products for pain management ...are available commercially, the implementation of a device that safely and reliably provides extended analgesia and is sufficiently flexible to facilitate a diverse array of release profiles would serve to advance patient comfort, quality of care and compliance following surgical procedures. Herein, we review current polymeric systems that could be utilized in new, controlled post-operative pain management devices and highlight where opportunities for improvement exist.
The remarkable elasticity and tensile strength found in natural elastomers are challenging to mimic. Synthetic elastomers typically feature covalently cross‐linked networks (rubbers), but this ...hinders their reprocessability. Physical cross‐linking via hydrogen bonding or ordered crystallite domains can afford reprocessable elastomers, but often at the cost of performance. Herein, we report the synthesis of ultra‐tough, reprocessable elastomers based on linear alternating polymers. The incorporation of a rigid isohexide adjacent to urethane moieties affords elastomers with exceptional strain hardening, strain rate dependent behavior, and high optical clarity. Distinct differences were observed between isomannide and isosorbide‐based elastomers where the latter displays superior tensile strength and strain recovery. These phenomena are attributed to the regiochemical irregularities in the polymers arising from their distinct stereochemistry and respective inter‐chain hydrogen bonding.
The stereochemical configurations of the rigid‐ring structures of isosorbide (ISPU) and isomannide (IMPU) direct strong hydrogen‐bonding interactions which impart unique properties including strain‐rate‐dependent behavior, significant strain hardening, and high optical clarity that are not possible using other chemical approaches to elastomer design.
Polymers are ubiquitous to almost every aspect of modern society and their use in medical products is similarly pervasive. Despite this, the diversity in commercial polymers used in medicine is ...stunningly low. Considerable time and resources have been extended over the years towards the development of new polymeric biomaterials which address unmet needs left by the current generation of medical-grade polymers. Machine learning (ML) presents an unprecedented opportunity in this field to bypass the need for trial-and-error synthesis, thus reducing the time and resources invested into new discoveries critical for advancing medical treatments. Current efforts pioneering applied ML in polymer design have employed combinatorial and high throughput experimental design to address data availability concerns. However, the lack of available and standardized characterization of parameters relevant to medicine, including degradation time and biocompatibility, represents a nearly insurmountable obstacle to ML-aided design of biomaterials. Herein, we identify a gap at the intersection of applied ML and biomedical polymer design, highlight current works at this junction more broadly and provide an outlook on challenges and future directions.
Additive manufacturing has the potential to revolutionize regenerative medicine, but the harsh thermal or photochemical conditions during the 3D printing process limit the inclusion of drugs, growth ...factors and other biologics within the resulting scaffolds. Functionalization strategies that enable specific placement of bioactive species on the surface of 3D printed structures following the printing process afford a promising approach to sidestep the harsh conditions and incorporate these valuable bioactive molecules with precise control over concentration. Herein, resorbable polymer scaffolds were prepared from propargyl functionalized L-phenylalanine-based poly(ester urea)s (PEUs). Osteogenic growth peptide (OGP) or bone morphogenic protein-2 (BMP-2) peptides were immobilized on PEU scaffolds through surface available propargyl groups via copper-catalyzed azide alkyne cycloaddition (CuAAC) post 3D printing. The presence of either OGP or BMP-2 significantly enhanced hMSCs osteogenic differentiation compared to unfunctionalized scaffolds.
Poly(propylene fumarate) star polymers photochemically 3D printed with degradable thiol cross-linkers yielded highly tunable biodegradable polymeric materials. Tailoring the alkene:thiol ratio (5:1, ...10:1, 20:1 and 30:1) and thus the cross-link density within the PPF star systems yielded a wide variation of both the mechanical and degradation properties of the printed materials. Fundamental trends were established between the polymer network cross-link density, glass transition temperature, and tensile and thermomechanical properties of the materials. The tensile properties of the PPF star-based systems were compared to commercial state-of-the-art non-degradable polymer resins. The thiolene-cross-linked materials are fully degradable and possess properties over a wide range of mechanical properties relevant to regenerative medicine applications.
Stereochemistry provides an appealing handle by which to control the properties of small molecules and polymers. While it is established that stereochemistry in linear polymers affects their bulk ...mechanical properties, the application of this concept to photocurable networks could allow for resins that can accommodate the increasing demand for mechanically diverse materials without the need to significantly change their formulation. Herein, we exploit cis and trans stereochemistry in pre-resin oligomers to create photoset materials with mechanical properties and degradation rates that are controlled by their stereochemistry and molecular weight. Both the synthesis of stereopure (cis or trans) acrylate-terminated pre-polymers and the subsequent UV-triggered cross-linking occurred with a retention of stereochemistry, close to 100%. The stereochemistry of a 4 kDa oligomer within the resin enabled the tuning of the formulation to either a fast eroding, soft cis elastomer or a stiff trans plastic that is more resistant to degradation. These results demonstrate that stereochemistry is a powerful tool to modify the stiffness, toughness, and degradability of high-resolution, three-dimensional printed scaffolds from the same formulated ratio of components.
PDF
