Abstract:The focus in the field of biomedical engineering has shifted in recent years to biodegradable polymers and, in particular, polyesters. Dozens of polyester-based medical devices are commercially available, and every year more are introduced to the market. The mechanical performance and wide range of biodegradation properties of this class of polymers allow for high degrees of selectivity for targeted clinical applications. Recent research endeavors to expand the application of polymers have been driven by a need to target the general hydrophobic nature of polyesters and their limited cell motif sites. This review provides a comprehensive investigation into advanced strategies to modify polyesters and their clinical potential for future biomedical applications.
The acidic nature of the degradation products of polyesters often leads to unpredictable clinical complications, such as necrosis of host tissues and massive immune cell invasions. In this study, poly(propylene carbonate) (PPC) and starch composite is introduced with superior characteristics as an alternative to polyester-based polymers. The degradation products of PPC-starch composites are mainly carbon dioxide and water; hence, the associated risks to the acidic degradation of polyesters are minimized. Moreover, the compression strength of PPC-starch composites can be tuned over the range of 0.2±0.03 MPa to 33.9±1.51 MPa by changing the starch contents of composites to address different clinical needs. More importantly, the addition of 50 wt % starch enhances the thermal processing capacity of the composites by elevating their decomposition temperature from 245 to 276 °C. Therefore, thermal processing methods, such as extrusion and hot melt compression methods can be used to generate different shapes and structures from PPC-starch composites. We also demonstrated the cytocompatibility and biocompatibility of these composites by conducting in vitro and in vivo tests. For instance, the numbers of osteoblast cells were increased 2.5 fold after 7 days post culture. In addition, PPC composites in subcutaneous mice model resulted in mild inflammatory responses (e.g., the formation of fibrotic tissue) that were diminished from two to 4 weeks postimplantation. The long-term in vivo biodegradation of PPC composites are compared with poly(lactic acid) (PLA). The histochemical analysis revealed that after 8 weeks, the biodegradation of PLA leads to massive immune cell infusion and inflammation at the site, whereas the PPC composites are well-tolerated in vivo. All these results underline the favorable properties of PPC-starch composites as a benign biodegradable biomaterial for fabrication of biomedical implants.
Injectable hydrogels made from extracellular matrix proteins such as elastin show great promise for various biomedical applications. Use of cytotoxic reagents, fixed gelling behavior, and lack of mechanical strength in these hydrogels are the main associated drawbacks. The aim of this study was to develop highly cytocompatible and injectable elastin-based hydrogels with alterable gelation characteristics, favorable mechanical properties and structural stability for load bearing applications. A thermoresponsive copolymer, poly(N-isopropylacrylamide-co-polylactide-2-hydroxyethyl methacrylate-co-oligo(ethylene glycol)monomethyl ether methacrylate, was functionalized with succinimide ester groups by incorporating N-acryloxysuccinimide monomer. These ester groups were exploited to covalently bond this polymer, denoted as PNPHO, to different proteins with primary amine groups such as α-elastin in aqueous media. The incorporation of elastin through covalent bond formation with PNPHO promotes the structural stability, mechanical properties and live cell proliferation within the structure of hydrogels. Our results demonstrated that elastin-co-PNPHO solutions were injectable through fine gauge needles and converted to hydrogels in situ at 37 °C in the absence of any crosslinking reagent. By altering PNPHO content, the gelling time of these hydrogels can be finely tuned within the range of 2 to 15 min to ensure compatibility with surgical requirements. In addition, these hydrogels exhibited compression moduli in the range of 40 to 145 kPa, which are substantially higher than those of previously developed elastin-based hydrogels. These hydrogels were highly stable in the physiological environment with the evidence of 10 wt% mass loss in 30 days of incubation in a simulated environment. This class of hydrogels is in vivo bioabsorbable due to the gradual increase of the lower critical solution temperature of the copolymer to above 37 °C due to the cleavage of polylactide from the PNPHO copolymer. Moreover, our results demonstrated that more than 80% of cells encapsulated in these hydrogels remained viable, and the number of encapsulated cells increased for at least 5 days. These unique properties mark elastin-co-PNHPO hydrogels as favorable candidates for a broad range of tissue engineering applications.
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