The past decade has witnessed an important shift in biomedical materials science, moving away from synthetic nanotechnology platforms, such as liposomes, polymeric nanoparticles, and carbon nanotubes, toward naturally derived micro- and nano-architectures [1], [2], [3], [4]. This transition has been driven by persistent challenges associated with synthetic carriers, including scalability limitations, batch-to-batch variability, immunogenicity, and long-term toxicity concerns that hinder clinical translation [3], [5], [6]. Among the emerging natural alternatives, Sporopollenin Exine Capsules (SECs) have garnered significant attention due to their unique combination of properties: chemical inertness, distinct physical robustness, uniform micro-architecture, and non-allergenic characteristics when appropriately processed [7], [8], [9]. Fundamentally, sporopollenin is a highly cross-linked organic biopolymer that constitutes the structural backbone of the outer exine layer in spores and pollen grains across the plant kingdom. Although its precise macromolecular structure remains partially elusive due to its resistance to chemical degradation, advanced spectroscopic studies have defined it as a complex network composed primarily of long-chain fatty acids, phenylpropanoids, and oxygenated aromatic rings [10], [11]. While native sporopollenin is a chemically intractable, cross-linked network without a defined single molecular weight, advanced mass spectrometric analysis has identified polyhydroxylated tetraketide-like repeating units of ~280 Da and oligomeric motifs ranging up to ~2500 Da, which assemble to form the robust exine capsule [10], [11]. This unique chemical architecture, evolutionarily developed to protect plant gametes from ultraviolet (UV) radiation, desiccation, and microbial attack, confers exceptional chemical inertness and physical robustness, establishing it as one of the toughest known biological materials [12]. Derived from the outer wall (exine) of plant pollen grains through alkaline and acidic processing, SECs retain the intricate surface morphology and mechanical resilience of their biological precursors while offering a biocompatible platform for encapsulation and controlled release applications [1], [13], [14]. This convergence of natural abundance, structural sophistication, and biomedical compatibility positions sporopollenin as a compelling candidate for next-generation drug delivery systems and tissue engineering scaffolds [4], [15].

The exploration of SECs as micro-encapsulation vehicles has garnered sustained scientific interest since the foundational study by [16] first established their potential for drug delivery. Following these early proofs of concept, the field has expanded significantly, with extensive research characterizing sporopollenin as one of the toughest natural biopolymers and exploring its functional versatility in materials science [11], [17]. Unlike earlier works that focused primarily on material characterization and isolation techniques, recent literature has increasingly attempted to synthesize the broadening scope of SEC applications; for instance, [12] provided a comprehensive overview of genetic and biochemical pathways. Similarly, [7] offered a significant foundational overview of sporopollenin's utility. However, their work, published three years ago, adopted a broad scope encompassing non-biomedical sectors such as energy storage and environmental remediation and remained largely descriptive in nature. While valuable for understanding the material's versatility, it predates the surge of high-precision engineering studies published between 2022 and 2025. Furthermore, as a narrative survey, it did not employ systematic methodologies to quantitatively benchmark pharmaceutical performance, leaving a gap in understanding the specific barriers to clinical translation. Most recently, the field has witnessed a surge in material engineering innovations in 2025 that addresses these complexities. Aylanc and colleagues have pioneered sustainable methods for producing high-purity sporopollenin bio-capsules from bee pollen [18], introduced clean photochemical strategies to reconfigure sporopollenin surfaces for enhanced biocompatibility [19], and provided critical insights into how the morphological features of natural microcarriers influence drug encapsulation and release performance [20].

However, despite these valuable contributions and the exponential surge in publications, the current literature landscape remains fragmented. Existing reviews have largely functioned as descriptive surveys of “what is possible,” focusing on the breadth of applications rather than critically evaluating the “translational gap” between benchtop success and clinical viability. The field currently suffers from an “Application Gap”, a disconnect where research is disproportionately concentrated on fundamental properties rather than cohesive strategies for clinical translation [4], [7]. To date, no study has employed a rigorous systematic methodology to quantitatively benchmark the performance of SECs, specifically in terms of loading efficiency, release kinetics, and in vivo safety, against established synthetic carriers.

To empirically define the scope of the current review amidst this expansion, we conducted a comprehensive bibliometric analysis of the research landscape from 1980 to 2024 (n = 1172 articles). This quantitative assessment revealed a distinct temporal discontinuity: research remained largely dormant and confined to fundamental palynology for three decades, followed by a dramatic “inflection point” in 2014 marked by exponential growth. This surge signals a shift from descriptive biological characterization (“What is sporopollenin?”) to functional application (“What can we do with it?”). Consequently, we restricted the temporal scope of this review to the “modern era” of sporopollenin research (2015–2025) to capture this explosion in biomedical material engineering and address the emerging “translational gap” identified in our dataset.

This manuscript addresses this critical deficiency by conducting the first systematic review Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) of the field's pivotal growth period (2015–2025). By moving beyond the narrative summaries found in previous works, this study provides a data-driven evaluation of pharmaceutical performance, thereby clarifying the precise technological and regulatory barriers preventing the clinical translation of this promising biomaterial. Consequently, this review addresses the following question: In biomedical applications such as drug delivery and tissue engineering (Population), how do SECs (Intervention) compare to traditional synthetic carriers or free drugs (Comparator) in terms of bioavailability, targeting efficiency, and biocompatibility (Outcome).