Wound healing, management, and early prosthetic rehabilitation: a scoping review of healing and non-healing definitions, physical biomarkers, and chemical biomarkers

BACKGROUND:
Post-amputation healing is a complex, multi-phase process (haemostasis, inflammation, proliferation, and remodelling) requiring precise cellular coordination. This process is hindered by complications such as infection and tissue necrosis [1,2], especially in individuals with comorbidities like diabetes [3], delaying prosthetic rehabilitation and impacting quality of life [4,5]. Current residuum healing assessments focus solely on surface examination [6]; identifying objective biomarkers may improve evaluations, guide rehabilitation timelines, and reduce complications in clinical practice.

AIM:
The project aimed to identify predictive, diagnostic, and/or indicative biomarkers (physical, chemical, or other) of healing or non-healing of the tissues and structures found in the residual limbs of adults with amputation.

METHOD:
A scoping review was conducted according to Joanna Briggs Institute (JBI) and PRISMA-ScR guidelines. On May 6, 2023, searches with terms “biomarkers”, “wound healing”, and “amputation” were carried out across Web of Science, Ovid MEDLINE, Ovid Embase, Scopus, Cochrane, PubMed, and CINAHL. Inclusion criteria included: (1) references to biomarkers and healing, (2) residuum tissue healing, (3) clear methodology with ethical approval, and (4) publication date from 2017 onwards. Articles were assessed for quality (QualSyst tool) and evidence level (JBI system). Data extraction categorized studies by type, wound, and model; biomarkers recurrent across categories were reported.

RESULTS:
Of the 3,306 articles screened, 219 met inclusion criteria, with 77% rated as strong quality. However, 43% did not define healing, and 84% lacked non-healing definitions, highlighting a lack of standardized criteria regardless of study type. Healing definitions included criteria like epithelialization (14% of 219 sources) and wound size reduction (28%), while non-healing was most commonly defined by complications (4%) or need for surgery (4%). Of 156 sources using physical biomarkers, histology appeared most frequently (64 sources) offering crucial diagnostic insights into cellular healing. Other physical biomarkers included oxygenation and haemodynamic measures like ankle-brachial index (25 sources). 203 sources used chemical biomarkers. 38 chemical biomarkers were identified. Interleukins (indicative) and HbA1c (predictive) were the most common, each cited in 50 sources. Additional markers included routine blood markers, growth factors, and proteins like matrix metalloproteinases.

DISCUSSION AND CONCLUSION:
This review advocates for biomarkers to provide quantitative insights into residuum health post-amputation, capturing infection risk, tissue adaptation, and responses to prosthetic use. Incorporating psychosocial factors, which affect recovery [7], is also essential. A comprehensive grading system is proposed, assessing both surface-level and deep tissue healing by integrating biomarkers, psychosocial metrics, and functional recovery outcomes for a more accurate assessment of post-amputation healing and prosthetic readiness.

REFERENCES:
[1]: Kumar D; 2015, J Clin Diagn Res.
[2]: Choo YJ; 2022, World J Clin Cases.
[3]: Patel S; 2019, Biomed Pharmacother.
[4]: Miller TA; 2020, Am J Phys Med Rehabil.
[5]: Geertzen JH; 2001, Prosthet Orthot Int.
[6]: Day JD; 2023, Prosthet Orthot Int.
[7]: Alessa M; 2022, Cureus.