Hybrid 3D Bioprinted Scaffolds for the Delivery of Peptide Therapeutics

Protein-based drugs have great potential owing to their high specificity, compatibility, and low toxicity, but they are not widely applicable owing to enzymatic degradation, instability, and poor absorption. Nanostructured hybrid scaffolds comprising bioprinting platforms are a revolutionary approach to confronting such challenges. The combination of natural and artificial polymers with inorganic nanomaterials creates hybrid scaffolds that offer safe environments to improve peptide stability and controlled release. Bioprinting platforms increase spatial accuracy to create personalized drug-delivery platforms with a structure modeled on the extracellular matrix to support complex tissue functions. Recent studies have clarified the therapeutic potential of such platforms. For example, self-assembled peptide hydrogels together with three-dimensional printed polycaprolactone scaffolds have greatly improved osteogenic differentiation and bone regeneration, reflecting their ability to stabilize peptides and support tissue repair. In similar studies, bioinks containing peptides have been used to create extracellular matrix-mimicry environments to improve cell adhesion and proliferation, reflecting their potential to support scaffold-peptide collaborations to improve drugdelivery functions. Aside from the peptide encapsulation approaches, the introduction of techniques such as electrospinning, microfluidics, and extrusion-based printing widens the window of opportunities for the design of hybrid nanoscaffolds that allow customized release profiles while maintaining peptide integrity. Key aspects include peptide-matrix interaction, scaffold degradation kinetics, and their biocompatibility, besides regulatory and translation challenges. Recent emerging directions like AI-guided scaffold design, bio-orthogonal chemistry, and stimuli-responsive nanomaterials also serve to improve prospects toward clinical applications. This review places hybrid bioprinted nanoscaffolds in the perspective of next-generation tools for peptide therapeutics with promising applications in cancer therapy, immunomodulation, and regenerative medicine.