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

Abstract

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 NH end groups that form a stiff matrix upon mixing. Cross-linking involves an immediate reaction between PEG-SC and PEG-NH that forms carbamate bonds and a delayed reaction of PEG-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.

Injectable Anhydrous Poly(ethylene glycol) Polymer Liquids Form Protein Depot for Extended Controlled Release Applications Via Rapid In Situ Gelation

“…Such a material would also interact with amine groups from embedded protein drugs. Moreover, they did not achieve controlled protein release over long periods of time . In a time frame of one day, the majority of the model protein bovine serum albumin was released for all different gel compositions.…”

“…Moreover, due to the absence of evaporating solvents, implants can also be prepared by 3D printing . Kelmansky et al have already shown that “neat biogels” can be prepared in a water-free manner through cross-linking with amine- and succinimidyl carbonate-functionalized 4armPEG2k precursors at 37 °C. , However, their material contained succinimidyl carbonate groups, that covalently bound to the tissue after injection. Such a material would also interact with amine groups from embedded protein drugs.…”

“…Moreover, they did not achieve controlled protein release over long periods of time. 23 In a time frame of one day, the majority of the model protein bovine serum albumin was released for all different gel compositions. In contrast, the controlled release of doxorubicin over a period of about 32 days showed that this system is better suited for the release of small molecules.…”

Hot Glue Gun Releasing Biocompatible Tissue Adhesive

“…An ideal bioadhesive should be liquid for ease of application but solidify quickly after administration . It should also maintain both adhesion and cohesion strength, biodegradability, elasticity, and biocompatibility .…”