In Situ Dual Cross-Linking of Neat Biogel with Controlled Mechanical and Delivery Properties.

Injectable biomaterials play a critical role in many biomedical applications. These materials, however, often have limitations in mechanical and drug-eluting properties attributed to their high water content and the weak secondary forces holding them together. Here we describe a new injectable material based on two complementary water-free, prepolymers modified with succinimidyl carbonate (SC) or with NH2 end groups that form a stiff matrix upon mixing. Cross-linking involves an immediate reaction between PEG4-SC and PEG4-NH2 that forms carbamate bonds and a delayed reaction of PEG4-SC with hydroxyl functional groups that forms carbonate bonds. The mechanical properties, swelling, and erosion kinetics of this biomaterial can be fine-tuned by varying the ratio between the two prepolymers. Bovine serum albumin and poorly water-soluble free base doxorubicin were readily loaded into this system, resulting in a high drug loading content attributed to the absence of water in the formulation. Controlled release over a period of 1 to 30 days was observed, depending on mixture composition and drug properties. The injectable nature of the formulation, its tailored mechanical properties, the fact that it can be cross-linked by two separate mechanisms, and its ability to incorporate and release hydrophilic and hydrophobic drugs make it very attractive as a drug delivery system.

Strong tissue glue with tunable elasticity.

Many bio-adhesive materials adhere weakly to tissue due to their high water content and weak structural integrity. Others provide desirable adhesive strength but suffer from rigid structure and lack of elasticity after administration. We have developed two water-free, liquid four-armed PEG pre-polymers modified with NHS or with NH2 end groups which upon mixing changed from liquids to an elastic solid. The sealant and adhesive properties increased with the amount of the %v/v PEG4-NHS pre-polymer, and achieved adhesive properties comparable to those of cyanoacrylate glues. All mixtures showed minimal cytotoxicity in vitro. Mixtures of 90%v/v PEG4-NHS were retained in the subcutaneous space in vivo for up to 14days with minimal inflammation. This material's combination of desirable mechanical properties and biocompatibility has potential in numerous biomedical applications. STATEMENT OF SIGNIFICANCE: Many bio-adhesive materials adhere weakly to tissue (e.g. hydrogels) due to their high water content and weak structural integrity. Others provide desirable mechanical properties but suffer from poor biocompatibility (e.g. cyanoacrylates). This study proposes a new concept for the formation of super strong and tunable tissue glues. Our bio-materials' enhanced performance is the product of new neat (without water or other solvents) liquid polymers that solidify after administration while allowing interactions with the tissue. Moreover, the elastic modulus of these materials could easily be tuned without compromising biocompatibility. This system could be an attractive alternative to sutures and staples since it can be applied more quickly, causes less pain and may require less equipment while maintaining the desired adhesion strength.