AbstractPolymethylmethacrylate (PMMA) bone cement extensively utilized for the treatment of osteoporotic vertebral compression fractures due to its exceptional handleability and mechanical properties. Nevertheless, the clinical application of PMMA bone cement is restricted by its poor bioactivity and excessively high modulus of elasticity. Herein, mineralized small intestinal submucosa (mSIS) was incorporated into PMMA to prepare a partially degradable bone cement (mSIS–PMMA) that provided suitable compressive strength and reduced elastic modulus compared to pure PMMA. The ability of mSIS–PMMA bone cement to promote the attachment, proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells was shown through cellular experiments carried outin vitro, and an animal osteoporosis model validated its potential to improve osseointegration. Considering these benefits, mSIS–PMMA bone cement shows promising potential as an injectable biomaterial for orthopedic procedures that require bone augmentation.