Beyond limits in bone repair: A hypothesis for 3D-printed, exosome-enhanced autograft substitutes

We hypothesize that a personalized 3D-printed hydroxyapatite scaffold augmented with autologous biological components (exosomes or mesenchymal stem cells) can address the challenge of large intercalary bone defects by enhancing bone regeneration.

Current treatments like autografts, allografts, and synthetic scaffolds have significant limitations, including donor site morbidity, immune rejection, and insufficient osteogenesis. In our proposed approach, patient-specific HA scaffolds are fabricated via 3D printing and infused with osteogenic factors from the patient’s bone marrow–derived MSCs or their exosomes. We will evaluate the osteogenic and angiogenic potential of these bio-enhanced constructs in preclinical models. Additionally, the scaffolds are designed with structural features (e.g., intramedullary pegs or plate-like extensions) to ensure stable fixation within the defect site. To test this hypothesis, a comparative study is envisioned with four groups: (1) an autologous bone graft (gold-standard control), (2) a 3D-printed HA scaffold without any biological augmentation, (3) a 3D-printed HA scaffold seeded with autologous MSCs, and (4) a 3D-printed HA scaffold seeded with autologous MSCs supplemented with their osteogenic exosomes.

Outcome measures will include the rate and quality of bone healing (time to graft incorporation and radiographic union), restoration of function, and complication rates (including any need for revision surgery). We will also assess biological endpoints such as new bone formation and vascularization using micro-CT imaging and histology.

If successful, this strategy would provide a customizable, biologically active alternative for critical-sized bone defects, reducing donor-site complications and preserving native bone function.