Mechanical properties and biocompatibility of in situ enzymatically cross-linked gelatin hydrogels.

OBJECTIVES: Gelatin, a degraded collagen, has been widely used as a scaffolding material in tissue engineering applications. In this work, we aimed at the development of in situ, cross-linking, cytocompatible hydrogels by the use of transglutaminase as a cross-linker for potential application in the regeneration of tissues. METHODS: Hydrogels were prepared from gelatin of different concentrations and bloom degree (175 (G175) or 300 (G300) bloom gelatin) and cross-linked with various amounts of microbial transglutaminase (mTG) at 37°C. Mechanical properties and cross-linking degree were studied by rheology and swelling experiments. Four hydrogels with different stiffness were selected for studies with embedded human adipose-derived stem cells (hASCs). RESULTS: Hydrogels were obtained with storage modulus (G') values between 11 (±1) Pa and 1,800 (±200) Pa with gelation times between 80 (±6) and 450 (±36) seconds. G300 cross-linked gelatin hydrogels displayed higher gel stiffness, lower swelling ratio and gelled more rapidly compared to the hydrogels prepared from G175. Stiffer hydrogels (50 and 200 Pa) showed greater ability to support the proliferation of hASCs than softer ones (11 and 30 Pa). The highest cell proliferation was observed with a hydrogel of 200 Pa modulus. CONCLUSIONS: Overall, transglutaminase cross-linked gelatin hydrogels might be suitable as injectable hydrogels for the engineering of musculoskeletal and other types of connective tissues.

New Aspects in the Formulation of Drugs Based on Three Case Studies.

The improvement of pharmaceutical dosage forms, such as tablets, towards drug delivery control and cost efficiency is of great importance in formulation technologies. Here, three examples: in situ coating, freeze casting and protein-based biocomposites are presented that address the above mentioned issues and contribute to further developments in formulation technologies. The in situ coating increases the economic efficiency by saving process steps in comparison to a conventional tableting process and provides a crystalline coating for a tailorable drug delivery rate. The freeze casting allows the control over the surface area of a drug delivery system (DDS) by providing different numbers and sizes of pores, which in conjunction with adequate additives offer an efficient instrument for drug delivery control, especially by accelerating the dissolution effect. Protein-based biocomposites are attractive materials for biomedical and pharmaceutical applications that can be applied as a polymeric DDS. They inherently combine degradability in vivo and in vitro, show a good biocompatibility, offer sites of adhesion for cells and may additionally be used to release embedded bioactive molecules. Here, a new approach regarding the incorporation of crystalline active pharmaceutical ingredients (API) into a protein matrix in one process step is presented. All three presented techniques mark decisive progress towards tailor-made drug delivery systems with respect to function, economic efficiency and the generation of additional values.