Wound management, healing, and early prosthetic rehabilitation : part 3 - a scoping review of chemical biomarkers

Williams-Reid, Hannelore and Johannesson, Anton and Buis, Arjan (2025) Wound management, healing, and early prosthetic rehabilitation : part 3 - a scoping review of chemical biomarkers. Canadian Prosthetics & Orthotics Journal, 8 (1). 1. ISSN 2561-987X (https://doi.org/10.33137/cpoj.v8i1.43717)

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Abstract

BACKGROUND: The prompt provision of lower limb weight-bearing prostheses diminishes healthcare expenses and mortality rates following amputation. Nonetheless, assessing readiness for a prosthesis remains subjective, underscoring the necessity for objective biomarkers to evaluate healing progression and avoid additional damage to the residual limb. OBJECTIVE(S): This review aimed to identify predictive, diagnostic, and indicative chemical biomarkers of healing of the tissues and structures found in the residual limbs of adults. METHODOLOGY: A scoping review was conducted following the JBI and PRISMA-ScR guidelines. Comprehensive searches using the terms “biomarkers,” “wound healing,” and “amputation” were performed across Web of Science, Ovid Medline, Ovid Embase, Scopus, Cochrane, PubMed, and CINAHL databases. Key inclusion criteria for the articles were: 1) References to biomarkers and healing; 2) Healing of residuum tissue; 3) Repeatable methodology with ethical approval. The included articles were evaluated for quality of evidence using the QualSyst tool and for the level of evidence using the JBI classification system. FINDINGS: Of 3,306 articles screened at the title and abstract level, 219 met the eligibility criteria for data extraction. Over 75% of sources were deemed to be of strong quality. 38 chemical biomarkers were repeated in multiple sources and study categories, with interleukins and HbA1c being the most common, appearing in 50 sources each. Further biomarkers included routine blood markers, growth factors, MMPs, and cellular markers (e.g. CD31 and α-SMA). CONCLUSION: Despite extensive research identifying numerous biomarkers, only routine blood markers are used in clinical practice, highlighting the need for integration of objective markers to enhance healing processes. No single biomarker can reliably indicate healing due to comorbidities and measurement location, necessitating the use of a range of biomarkers for improved objectivity. Continuous measurement over the healing timeframe is crucial, as biomarker levels change and impact healing stages. Improved measurement techniques are needed to bridge the gap between research and clinical application. DATA STATEMENT: All data underpinning this publication are openly available from the University of Strathclyde KnowledgeBase at https://doi.org/10.15129/f5044ee8-5689-49c2-a67a-1cbe26af8a58.

ORCID iDs

Williams-Reid, Hannelore ORCID logoORCID: https://orcid.org/0009-0009-3225-6581, Johannesson, Anton and Buis, Arjan ORCID logoORCID: https://orcid.org/0000-0003-3947-293X;