The quality of bone formed around the implants warrants further investigation

The gap

Evidence profile

Sourced from the future work and limitations of the source papers, classified as general, spanning 3 journals. Those papers have been cited 7 times in total.

Supporting evidence — 4 representative gaps

• Partial-EMT in oral squamous cell carcinoma: molecular circuitry and clinical translation (2026) · International Journal of Oral Science · cited 3× · doi

  Addressing the challenges posed by partial-EMT in OSCC will require coordinated efforts across several key areas. First, the integration of multi-omics data—including genomics, transcriptomics, proteomics, and epigenomics—will be essential for elucidating the molecular mechanisms and regulatory networks that drive partial-EMT. This systems-level approach can identify key regulators and signaling pathways, clarifying the complex relationship between EMT states and tumor progression. Advanced sequencing technologies, parti- cularly single-cell and spatial platforms, enable detailed profiling of cellular phenotypes and interactions within the TME. These tools allow researchers to assess the stability of hybrid states and map their spatial context, offering insight into their biological and clinical relevance. Emerging spatial technologies, such as spatial transcrip- tomics and proteomics, offer practical solutions to current limitations in studying partial-EMT. By directly mapping gene and protein expression within tissue architecture, these tools can reveal the enrichment of partial-EMT programs at the invasive front and quantify their spatial associations with CAFs and immune cells. Spatial readouts can also distinguish early and late partial-EMT states by detecting coordinated expression of motility, matrix-interaction, and immune-exclusion modules—while preserving epithelial fea- tures. Targeted spatial panels focusing on epithelial, mesenchymal,

  generalfuture work
  Keywords: spatial partial states coordinated proteomics technologies within tools expression immune epithelial addressing challenges posed oscc
• Functionalizing biomaterials for osseointegration – microRNAs at the crossroads of bone formation and immune modulation (2026) · Bone & Joint Research · doi

  miRNAs are emerging as powerful regulators of osteo- blast diferentiation and bone formation, exerting their efects through post-transcriptional control of key signalling pathways. Numerous miRNAs have been shown to modu- late critical phases of osteogenesis, osteoclastogenesis, and macrophage polarization, thereby linking bone regeneration with immune modulation.169–171 Despite increasing evidence from in vitro and in vivo studies on bone regeneration and osteoimmunology, there is limited direct evidence connecting specifc miRNAs to improved osseointegration. Thus, while the application of miRNA-based therapies in the context of implant integration is biologically plausible, it remains largely hypothetical and requires further validation.125,172 Osseointe- gration is a complex process that is regulated by a wide range of miRNAs. These miRNAs, many of which remain unidenti- fed or incompletely characterized, control cell proliferation, osteoblast diferentiation, ECM synthesis, and matrix miner- alization.171 Several miRNAs, such as those of the miR-21, miR-155, miR-451, and miR-181 families, have been presented in this review, which both modulate osteoblast and osteo- clast activity as well as immune cell behaviour, suggesting a coordinated regulatory network. However, their efects are not generally defned and depend on the specifc conditions of the experiment. This alignment suggests that miRNAs act as shared molecular regulators at the bone-immune interface, thereby synchronizing infammatory cues with osteogenic responses. These fndings propose the potential of miRNA- based strategies to improve bone regeneration by infuencing both immune responses and bone formation.

  generalfuture work
  Keywords: mirnas bone immune regeneration regulators osteo diferentiation formation efects control thereby evidence specifc mirna based
• The missing code in osseointegration: A genome-wide review of RNA sequencing in implant integration (2026) · Journal of Prosthodontic Research · cited 2× · doi

  The next phase in implant biology will likely involve multi-omics approaches that integrate transcriptomics with proteomics, metabo- lomics, epigenomics, and spatial transcriptomics. RNA-seq identifies DEGs; however, proteomic analysis is necessary to confirm which proteins are synthesized and functionally active. Metabolomics com- plements this by capturing shifts in energy metabolism, oxidative stress, and signaling intermediates, whereas epigenomics provides insights into chromatin-level regulation and ncRNAs activity. Spatial transcriptomics further adds a critical dimension by mapping gene expression patterns to defined peri-implant regions, such as bone- contacting zones, soft tissue interfaces, and inflammatory fronts, allowing direct visualization of how specific surface topographies or chemistries modulate local tissue responses. Bulk RNA-seq aver- ages signals from mixed cell populations, whereas single-cell RNA sequencing profiles gene expression at the individual cell level to identify distinct subtypes and their transcriptional dynamics. When combined with spatial transcriptomics, these technologies allow true spatiotemporal analysis, revealing how osteogenic, fibroblastic, and immune cells organize and interact within localized tissue niches during osseointegration. As these analytical frameworks evolve, they will inform the rational design of next-generation surface chemis- tries and coatings that actively regulate gene expression networks, promote osteogenesis, enhance soft tissue sealing, and maintain immune homeostasis. The convergence of these approaches will transform implant surface engineering from an empirical process to a data-driven discipline grounded in systems biology. Experimental systems should evolve with analytical advances to better replicate in vivo environments. Recently, a three-dimensional dynamic implant culture model was developed to allow osteoblasts to attach, proliferate, and mineralize on implant surfaces under controlled mechanical motion. This platform enables the evaluation of surface-dependent biological performance under physiologically relevant conditions, bridging the gap between static assays and in vivo osseointegration research[90]. When combined with multi- omics analysis, such dynamic 3D models can reveal context-depen- dent signaling networks that remain undetectable in conventional two-dimensional cultures. From a translational perspective, RNA-seq offers a path toward predictive diagnostics and personalized implant therapies. Dif- ferential gene expression signatures may serve as early biomarkers to distinguish successful osseointegration, enabling clinicians to stratify risks and adapt treatment strategies. For example, increased inflammatory gene expression could help identify patients who may benefit from immunomodulatory surfaces or adjunctive anti- inflammatory therapies. Similarly, exosome-derived miRNA profiles may emerge as non-invasive biomarkers of peri-implant tissue health, enabling real-time monitoring of integration. Such applica- tions could transform implantology from a field rooted in empiricism to one driven by precision medicine.

  generalfuture work
  Keywords: implant gene expression tissue transcriptomics surface spatial inflammatory cell osseointegration next biology multi omics approaches
• The missing code in osseointegration: A genome-wide review of RNA sequencing in implant integration (2026) · Journal of Prosthodontic Research · cited 2× · doi

  Additionally, the quality of bone formed around the implants warrants further investigation. These fundamental observations high- light the fact that even the most basic elements of osseointegration biology remain incompletely defined at the molecular level. Furthermore, patient-related factors known to compromise implant outcomes, such as diabetes, osteoporosis, and aging, have rarely been investigated using transcriptomic tools.

  generallimitations
  Keywords: additionally quality bone formed around implants warrants further investigation fundamental observations high light fact even

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