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Development of bifunctional scaffolds, which can achieve cell adhesion and controlled release of protein drugs, is very promising in bone tissue engineering.Owing to their biocompatibility and injectablity, poly(lactide-co-glycolide acid) (PLGA) porous microspheres (PLGA-pMS) present potential scaffolds in bone tissue engineering.However, their application is greatly hampered by low encapsulation efficiency, burst release of protein drugs, and hydrophobicity which leads to poor cell adhesion.To overcome these drawbacks, we developed novel PLGA-pMS, defined as chitosan microspheres/PLGA porous microspheres (CS-MS/PLGA-pMS), by incorporating bovine serum albumin (BSA) loaded chitosan microspheres (CS-MS) into Gly-Arg-Gly-Asp-Ser-Pro-Cys (GRGDSPC) modified PLGA-pMS (Scheme 1).GRGDSPC is aArg-Gly-Asp (RGD) containing peptide used to enhance the hydrophilicity and cell affinity of the porous microspheres.The results showed that PLGA-pMS had a size of 446.77 ± 19.46 μm, with an average surface pore size of 19.67 ± 2.91 μm, whereas CS-MS had a size of 15.37 ± 7 μm (cross-linked with 5% sodium tripolyphosphate (TPP)) or 16.44 ± 7.41 μm (cross-linked with 10% TPP).Scanning electron microscopy (SEM) revealed that CS-MS was partly embedded in the PLGA polymer matrices and the integrity of CS-MS was retained (Fig 1).Thermogravimetry analyzer (TGA) also demonstrated that CS-MS were incorporated into PLGA-pMS in CS-MS/PLGA-pMS.The CS-MS/PLGA-pMS had a size of 454.02 ± 16.09 μm, with a BSA encapsulation efficiency of 62.16 ± 3.44% (10% TPP prepared CS-MS) and 53.19 ± 1.67% (5% TPP prepared CS-MS).Strikingly, CS-MS/PLGA-pMS prepared with 5% TPP exhibited a sustained BSA release for 23 days (Fig 2).Modification of GRGDSPC significantly improved adhesion and proliferation of human osteoblast-like MG-63 cells on the porous microspheres.Cell viability correlated positively with the modification degree of GRGDSPC (from 0% to 30%, w/v), as shown in Fig 3.In conclusion, CS-MS/PLGA-pMS may act as potential bifunctional scaffolds for bone tissue engineering.