Electronic health record mining reveals effects of patient immune status on clinical outcomes of biomaterial implantation following skeletal muscle damage

ABSTRACT Implantation of medical devices and biomaterials can help restore form and function of missing or damaged tissue. It is known that the immune system plays a critical role in both positive and negative outcomes of these implanted materials. The foreign body response is characterized by protein deposition and clotting followed by macrophage inflammation, frustrated phagocytosis, giant cell formation, and ultimately fibrosis. This can inhibit the function of implanted devices (e.g. Insulin pumps) as well as cosmesis (e.g. capsular contracture in breast implants) and persistent inflammation has been associated with more severe outcomes in some patients, including emergence of autoimmune-like pathologies. On the other hand, the immune system plays a constructive role in tissue remodeling and regeneration and is needed for the positive effects of some biomaterials, such as extracellular matrix-based scaffolds in muscle repair. Given these factors, we sought to understand potential variations in post-operative complications in individuals with primary and secondary immune disorders – both autoimmune and immunodeficiencies. This preliminary observational study using electronic health record mining showed increased complication odds for individuals with both autoimmune conditions and immunodeficiencies, with variations dependent upon the individual’s sex and age as well as the type of material implanted. Future prospective studies could yield improved insight into both mechanisms of immune response to materials in humans and identify potential risk factors for individual patients undergoing plastics and reconstructive surgeries. Competing Interest Statement The authors have declared no competing interest. Funding Statement This work was funded by the intramural research program of the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health (NIH). Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: TriNetX (https://trinetx.com/) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes DATA AVAILABILITY Electronic health record (EHR) data were analyzed through the TriNetX platform which provides aggregate analyses. All generated odds ratios and estimates provided by TriNetX are available in Supplemental Data File 1.