Extracellular environments significantly affect cell proliferation, differentiation, and functions. The extracellular environment changes during many physiological and pathological processes such as embryo development, wound healing, and tumor growth. To mimic these changes, we developed novel thiol−maleimide clickable alginate microcapsules, which can introduce thiol-containing peptides by "in situ conjugation" with maleimide-modified alginate, even in serum-containing cell culture media. Additive peptides were rapidly concentrated into microcapsules by a diffusionreaction process in the capsule. The proliferation of encapsulated fibroblasts was accelerated by in situ conjugation of CRGDS, while free RGDS showed no effect. Moreover, encapsulated preosteoblastic cells started osteogenic differentiation via in situ conjugation of BMP-2 mimetic peptides such as CDWIVA and CG-BMP-2 knuckle epitope peptide, while BMP-2 did not induce differentiation of the encapsulated cells. Especially in tissue engineering, accurate and inexpensive methods for inducing cell differentiation are required. We believe that this in situ conjugation approach employing various functional peptides will be useful in biomedical, bioindustrial, and biochemical fields in the future.

We fabricated ferric ion-cross-linked hydrogels of a chelating hyaluronic acid (HA) derivative. HA was conjugated with iminodiacetic acid (IDA) at 22% of a modification degree to its disaccharide unit of HA. This conjugate (HA–IDA) showed degradability by hyaluronidase even after the IDA modification, and its degradation rate was almost the same as that of HA. HA–IDA and HA formed hydrogels (FeHA and FeHA–IDA) by cross-linking with ferric ions (Fe3+). The storage modulus of FeHA–IDA was ca. 100 Pa, which was higher than ca. 10 Pa of FeHA. FeHA–IDA showed excellent biocompatibility to a mesothelium cell line as well as rapid degradation. Above all, FeHA–IDA showed efficacy in reducing adhesion formation in a rat sidewall defect-bowel abrasion model.