Tissue losses and organ failures resulting from injuries or diseases remain frequent and serious health problems despite great advances in medical technologies. Transplantation and reconstructive surgeries are seriously challenged by donor tissue shortage. We take a tissue engineering approach to design 3D scaffolds for cells to grow and synthesize new tissues. The scaffolds are biodegradable and will be absorbed after fulfilling the purpose as 3D templates, leaving nothing foreign in the body. To better mimic natural bone structurally, mechanically and biologically, nano-sized hydroxyapatite particles (N-HAP) were formulated with biodegradable poly(α-hydroxyl acids) to form composite scaffolds with well-controlled pore structures using thermally induced phase separation (TIPS) in this work. The pore structure and mechanical properties of the scaffolds were optimized by the use of multiple solvent systems, different quenching rates and quenching depths. The fabricated scaffolds possessed porosities higher than 90% and average pore sizes ranging from 50 to 500 μm. The scaffolds containing N-HAP maintained open and regular 3D pore structure similar to those of plain polymer scaffolds, implying that N-HAP particles were dispersed within the polymer pore walls of the scaffolds. The addition of N-HAP increased the compressive modulus by 20∼80% over that of plain polymer scaffolds. These results indicate that poly(α-hydroxyl acids)/N-HAP scaffolds may provide excellent 3D substrates for bone tissue engineering.