To　mimic　the　mineral　component　and　the　microstructure　of　natural　bone,　nanohydroxyapatite　(nHAP)/polymer　(natural　and　synthetic　materials)　composite　scaffolds　with　micropore　structures　and　good　mechanical　performance　were　prepared　via　the　assistance　of　sonication　and　amidation.　Scanning　electron　microscopy　(SEM)　and　X-ray　diffraction　(XRD)　showed　the　biomimetic　homogeneous　formation　of　nHAP　in　the　polymer　matrix.　Fourier　transform　infrared　spectroscopy　(FTIR)　indicated　that　the　polymer　matrix　regulated　the　crystallization　of　nHAP.　The　integration　of　synthetic/natural　polymers　benefited　nHAP　crystallization　in　the　polymer　matrix　and　thus　improved　the　mechanical　performance　of　the　chitosan　(CS)/collagen　(Col)/poly　(lactic　acid)　(PLA)/nHAP　scaffolds.　The　in　vitro　bioactivity　ability　was　investigated　by　incubating　in　a　simulated　body　fluid　(SBF).　The　methyl　thiazolyl　tetrazolium　(MTT)　test,　the　acridine　orange/ethidium　bromide　(AO/EB)　and　Giemsa　staining　showed　that　the　scaffolds　had　good　biocompatibility　and　could　maintain　the　cell　growth.　Therefore,　the　CS/Col/PLA/nHAP　scaffold　is　promising　for　bone　tissue　engineering　applications.