Work

Biomaterials and Bioprinting Strategies for Regenerative Medicine: A Systematic Review of Design and Translation

Year: 2026
Type: review
Study design: Systematic Review
Abstract: This systematic review synthesizes and critically evaluates current biomaterials and bioprinting technologies for regenerative medicine, focusing on dynamic, immunomodulatory, and scalable strategies that address persistent translational barriers. We conducted a systematic literature search across five core dimensions: stimuli responsive 4D bioprinting, immunomodulatory bioinks, rheology printability trade offs in multi material jetting, biomechanical heterogeneity for osteochondral regeneration, and scalability constraints in light based bioprinting. A purposive sample of forty to sixty articles was selected based on predefined inclusion criteria, with standardized data extraction across eleven field categories. The evidence base for the major conclusions varied across these five thematic dimensions, and quantitative values reported below represent findings from specific subsets or individual studies rather than pooled estimates across the entire review sample. Studies addressing dynamic and 4D bioprinting consistently indicated that stimuli responsive bioinks can shift tissue maturation from a passive post printing process toward a programmable, stimulus guided trajectory. In one representative experimental study within this evidence subset, 4D bioprinted cartilage constructs achieved a glycosaminoglycan to DNA ratio of 10.3 and 125.8 fold type II collagen upregulation without exogenous growth factors. Evidence from studies examining immunomodulatory bioinks suggested that these materials can promote local reparative M2 macrophage polarization and angiogenesis, although the strength of this conclusion reflects the limited number of studies directly evaluating immune modulation. Across studies focused on inkjet and multi material printing, rheological findings generally supported a workable viscosity range of approximately 3–30 millipascal seconds, while several studies identified staged crosslinking as a strategy for balancing printing fidelity and cell viability. Studies of osteochondral constructs further showed that spatial stiffness gradients can influence mesenchymal stem cell differentiation toward chondrogenic phenotypes in softer regions and osteogenic phenotypes in stiffer regions; however, the apparent advantage of multi cue heterogeneity over stiffness alone was supported by a smaller subset of comparative studies. The studies examining light based bioprinting most frequently identified limited light penetration and photoinitiator associated cytotoxicity as scalability constraints, with a subset reporting that visible light systems and optimized photoinitiator concentrations may mitigate these limitations. The principal contribution of this work is the identification of recurring parameter ranges and design principles across the reviewed evidence, rather than universally established optimal values, including dynamic maturation, immunomodulatory programming, rheological optimization, biomechanical patterning, and advanced photoinitiation that collectively represent promising, but still context dependent, pathways for clinical translation. Nevertheless, interdisciplinary optimization of material process biology interactions remains essential for realizing functional regenerative therapies.
Language: English
Open Access status: diamond
OpenAlex ID: W7219930205
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