The existing surgical adhesives are not ideal for wet tissue adhesion required in many surgeries such as those for internal organs. Developing surgical adhesives with strong wet tissue adhesion, controlled degradability and mechanical properties, and excellent biocompatibility has been a significant challenge. Herein, learning from nature, we report a one-step synthesis of a family of injectable citrate-based mussel-inspired bioadhesives (iCMBAs) for surgical use. Within the formulations investigated, iCMBAs showed 2.5–8.0 folds stronger wet tissue adhesion strength over the clinically used fibrin glue, demonstrated controlled degradability and tissue-like elastomeric mechanical properties, and exhibited excellent cyto/tissue-compatibility both in vitro and in vivo. iCMBAs were able to stop bleeding instantly and suturelessly, and close wounds (2 cm long × 0.5 cm deep) created on the back of Sprague-Dawley rats, which is impossible when using existing gold standard, fibrin glue, due to its weak wet tissue adhesion strength. Equally important, the new bioadhesives facilitate wound healing, and are completely degraded and absorbed without eliciting significant inflammatory response. Our results support that iCMBA technology is highly translational and could have broad impact on surgeries where surgical tissue adhesives, sealants, and hemostatic agents are used.

The need for advanced materials in emerging technologies such as tissue engineering has prompted increased research to produce novel biodegradable polymers elastic in nature and mechanically compliant with the host tissue. We have developed a soft biodegradable elastomeric platform biomaterial created from citric acid, maleic anhydride, and 1,8-octanediol, poly(octamethylene maleate (anhydride) citrate) (POMaC), which is able to closely mimic the mechanical properties of a wide range of soft biological tissues. POMaC features a dual crosslinking mechanism, which allows for the option of the crosslinking POMaC using UV irradiation and/or polycondensation to fit the needs of the intended application. The material properties, degradation profiles, and functionalities of POMaC thermoset networks can all be tuned through the monomer ratios and the dual crosslinking mechanism. POMaC polymers displayed an initial modulus between 0.03 and 1.54 MPa, and elongation at break between 48% and 534% strain. In vitro and in vivo evaluation using cell culture and subcutaneous implantation, respectively, confirmed cell and tissue biocompatibility. POMaC biodegradable polymers can also be combined with MEMS technology to fabricate soft and elastic 3D microchanneled scaffolds for tissue engineering applications. The introduction of POMaC will expand the choices of available biodegradable polymeric elastomers. The dual crosslinking mechanism for biodegradable elastomer design should contribute to biomaterials science.

Herein, we report the first citric acid (CA)-derived in situ crosslinkable biodegradable polymer, poly (ethylene glycol) maleate citrate (PEGMC). The synthesis of PEGMC could be carried out via a onepot polycondensation reaction without using organic solvents or catalysts. PEGMC could be insitu crosslinked into elastomeric PPEGMC hydrogels. The performance of hydrogels in terms of swelling, degradation, and mechanical properties were highly dependent on the molar ratio of monomers, crosslinker concentration, and crosslinking mechanism used in the synthesis process. Cyclic conditioning tests showed that PPEGMC hydrogels could be compressed up to 75% strain without permanent deformation and with negligible hysteresis. Water-soluble PEGMC demonstrated excellent cytocompatibilty in vitro. The degradation products of PPEGMC also showed minimal cytotoxicity in vitro. Animal studies in rats clearly demonstrated the excellent injectability of PEGMC and degradability of the in situ-formed PPEGMC. PPEGMC elicited minimal inflammation in the early stages post-injection and was completely degraded within 30 days in rats. In conclusion, the development of CA-derived injectable biodegradable PEGMC presents numerous opportunities for material innovation and offers excellent candidate materials for in situ tissue engineering and drug delivery applications.

Polymeric nanoparticles (NPs) are promising carriers of biological agents to lung due to advantages including biocompatibility, ease of surface modification, localized action and reduced systemic toxicity. However, there have been no studies extensively characterizing and comparing the behavior of polymeric NPs for pulmonary protein/DNA delivery both in vitro and in vivo. We screened six polymeric NPs: gelatin, chitosan, alginate, poly lactic-co-glycolic acid (PLGA), PLGA-chitosan, and PLGA-polyethylene glycol (PEG), for inhalational protein/ DNA delivery. All NPs except PLGA-PEG and alginate were <300 nm in size with bi-phasic core compound release profile. Gelatin, PLGA NPs and PLGA-PEG NPs remained stable in deionized water, serum, saline and simulated lung fluid (Gamble’s solution) over 5 days. PLGA-based NPs and natural polymer NPs exhibited highest cytocompatibility and dose-dependent in vitro uptake respectively by human alveolar type-1 epithelial cells. Based on these profiles, gelatin and PLGA NPs were used to encapsulate a) plasmid DNA encoding yellow fluorescent protein (YFP) or b) rhodamine-conjugated erythropoietin (EPO) for inhalational delivery to rats. Following a single inhalation, widespread pulmonary EPO distribution persisted for up to 10 days while increasing YFP expression was observed for at least 7 days for both NPs. The overall results support both PLGA and gelatin NPs as promising carriers for pulmonary protein/DNA delivery.