Additive manufacturing (AM) has emerged over the past four decades as a cost-effective, on-demand modality for fabrication of geometrically complex objects. The ability to design and print virtually any object shape using a diverse array of materials, such as metals, polymers, ceramics and bioinks, has allowed for the adoption of this technology for biomedical applications in both research and clinical settings. Current advancements in tissue engineering and regeneration, therapeutic delivery, medical device fabrication and operative management planning ensure that AM will continue to play an increasingly important role in the future of healthcare. In this review, we outline current biomedical applications of common AM techniques and materials.

The spine is the most common site of bone metastasis, often originating from prostate, lung, and breast cancers. High systemic doses of chemotherapeutics such as doxorubicin (DOX), cisplatin, or paclitaxel often have severe side effects. Surgical removal of spine metastases also leaves large defects which cannot spontaneously heal and require bone grafting. To circumvent these issues, we designed an approach for local chemotherapeutic delivery within 3D-printed scaffolds which could also potentially serve as a bone substitute. Direct treatment of prostate cancer cell line LAPC4 and patient derived spine metastases cells with 0.01 µM DOX significantly reduced metabolic activity, proliferation, migration, and spheroid growth. We then assessed uptake and release of DOX in a series of porous 3D-printed scaffolds on LAPC4 cells as well as patient-derived spine metastases cells. Over seven days, 60–75% of DOX loaded onto scaffolds could be released, which significantly reduced metabolic activity and proliferation of both LAPC4 and patient derived cells, while unloaded scaffolds had no effect. Porous 3D-printed scaffolds may provide a novel and inexpensive approach to locally deliver chemotherapeutics in a patient-specific manner at tumor resection sites. With a composite design to enhance strength and promote sustained drug release, the scaffolds could reduce systemic negative effects, enhance bone repair, and improve patient outcomes.

Bisphosphonates (BPs) including zoledronate (zol) have become standard care for bone metastases as they effectively inhibit tumor-induced osteolysis and associated pain. Several studies have also suggested that zol has direct anti-tumor activity. Systemic administration at high doses is the current approach to deliver zol, yet it has been associated with debilitating side effects. Local therapeutic delivery offers the ability to administer much lower total dosage, while at the same time maintaining sustained high-local drug concentration directly at the target treatment site. Here, we aimed to assess effects of lower doses of zol on bone metastases over a longer time. Prostate cancer cell line LAPC4 and prostate-induced bone metastasis cells were treated with zol at 1, 3 and 10 µM for 7 days. Following treatment, cell proliferation was assessed using Almarblue®, Vybrant MTT®, and Live/Dead® viability/cytotoxicity assays. Additionally, cell migration and invasion were carried out using Falcon™ cell culture inserts and Cultrex® 3D spheroid cell invasion assays respectively. We show that treatment with 3–10 µM zol over 7-days significantly decreased cell proliferation in both the prostate cancer cell line LAPC4 and cells from spine metastases secondary to prostate cancer. Using the same low-dose and longer time course for treatment, we demonstrate that 10 µM zol also significantly inhibits tumor cell migration and 3D-cell growth/invasion. This project harnesses the potential of using zol at low doses for longer treatment periods, which may be a viable treatment modality when coupled with biomaterials or biodevices for local delivery.

Limitations of bone defect reconstruction include poor bone healing and osteointegration with acrylic cements, lack of strength with bone putty/paste, and poor osteointegration. Tissue engineering aims to bridge these gaps through the use of bioactive implants. However, there is often a risk of infection and biofilm formation associated with orthopedic implants, which may develop anti-microbial resistance. To promote bone repair while also locally delivering therapeutics, 3D-printed implants serve as a suitable alternative. Soft, nanoporous 3D-printed filaments made from a thermoplastic polyurethane and polyvinyl alcohol blend, LAY-FOMM and LAY-FELT, have shown promise for drug delivery and orthopedic applications. Here, we compare 3D printability and sustained antibiotic release kinetics from two types of commercial 3D-printed porous filaments suitable for bone tissue engineering applications. We found that both LAY-FOMM and LAY-FELT could be consistently printed into scaffolds for drug delivery. Further, the materials could sustainably release Tetracycline over 3 days, independent of material type and infill geometry. The drug-loaded materials did not show any cytotoxicity when cultured with primary human fibroblasts. We conclude that both LAY-FOMM and LAY-FELT 3D-printed scaffolds are suitable devices for local antibiotic delivery applications, and they may have potential applications to prophylactically reduce infections in orthopedic reconstruction surgery.