Abstract Progress in tissue engineering and regenerative medicine relies heavily on the development of novel scaffold materials. In this work, we created porous composite scaffolds of polyglycerol sebacate (PGS) and gelatine (G) through desolvation and lyophilization to achieve a well-balanced nanostructured porous material with desirable properties. Spectroscopic analysis confirmed the uniform integration of PGS elastomer and gelatine in the composite, with a composite with an optimised ratio of gelatine to PGS of 2:1 providing a required level of bioactivity, biodegradability and elasticity for soft tissue engineering applications. Introducing hydroxyapatite (HAP) into the composite mixture prior to lyophilization at an optimised weight ratio of HAP to gelatine to PGS of 6:3:1 resulted in a composite (HAP-GPGS) that closely simulates the microenvironment afforded by the native bone extracellular matrix, with PGS providing scaffold flexibility, and gelatin and hydroxyapatite promoting cell adhesion and osteoconduction. FTIR spectroscopy confirmed uniform distribution of constituents throughout the HPG scaffold, with the nanostructure and porosity mimicking the structural architecture of the cancellous bone matrix, as shown by SEM. Both GPGS and HAP-GPGS scaffolds were found to be non-cytotoxic and conducive to proliferation of MG63 (human osteoblast) and 3T3 (mouse fibroblast) cell lines, with the results of the MTT assay demonstrating excellent cellular viability and proliferation on the composite surfaces. Furthermore, the osteogenic potential of the scaffolds was evaluated through Alkaline Phosphatase (ALP) assay. Phase contrast microscopy and Fluorescence microscopy used to visualize cell-scaffold interactions showed robust cell attachment and healthy cell morphology with high viability, confirming the biomimetic nature of both composites. While the GPGS composite promoted the development of soft tissue-like structures, suggesting wound healing and soft tissue engineering applications, the significant enhancement in osteogenic differentiation in MG63 cells on the surface of HAP-GPGS scaffolds confirms their suitability for bone regeneration. These findings suggest that composites based on GPGS and HAP-GPGS have the desirable combination of characteristics, such as simple, low-cost fabrication from abundant resources, ability to fine-tune properties without the need to change scaffold preparation protocol, and highly biocompatible and osteoconductive nature of thus-produced materials.
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