PURPOSE: A manufacturing method of microsphere - hydro gel composite in which growth factor protein is dipped is provided to omit sterilization process or organic solvent use in conventional protein drug delivery formulation to resolve problems followed by the sterilization process or organic solvent. CONSTITUTION: A manufacturing method of microsphere - hydro gel composite in which growth factor protein is dipped comprises the following steps: preparing porous B-TCP microsphere; dipping the growth factor protein in the microsphere; and obtaining a composite of poloxamer hydro gel and porous B-TCP microsphere by mixing the porous B-TCP microsphere with temperature sensitive poloxamer hydro gel using 3-way connector. The sintering temperature of the porous B -TCP microsphere is 1050-1250 deg. Celsius, and the initial concentration before mixing the poloxamer hydro gel with the microsphere is 33-37 wt%. The porous B -TCP microsphere has particle size of 45-75 micro meters. The sintering temperature of the porous B -TCP microsphere is 1050 deg. Celsius, and the initial concentration is 35 wt%. The porous B -TCP microsphere and poloxamer hydro gel are mixed at the same mass. [Reference numerals] (AA) BMP-2 load porous microsphere; (BB) High concentration poloxamer hydrogel; (CC) Mixing by using 3 way connector; (DD) Microsphere-hydrogel carrier which loads the BMP-2본 발명은 인-시츄 프로세스로 성장인자 단백질을 담지한 마이크로스피어-하이드로겔 복합체의 제조방법에 관한 것으로, 다공성 β-TCP 마이크로스피어를 준비하는 단계; 상기 마이크로스피어에 성장인자 단백질을 담지하는 단계; 및 상기 성장인자 단백질을 담지한 상기 다공성 β-TCP 마이크로스피어와 온도감응형 폴록사머 하이드로겔을 3방향 커넥터를 이용하여 혼합하여 다공성 β-TCP 마이크로스피어와 폴록사머 하이드로겔의 복합체를 얻는 단계를 포함하는 것을 특징으로 하는 성장인자 단백질을 담지한 마이크로스피어-하이드로겔 복합체의 제조방법을 제공한다.