A Comprehensive Review of Clinical Studies on Bacterial Cellulose: From the Earliest Uses to Contemporary Innovations

Abstract

Bacterial cellulose (BC), a biopolymer produced by Gram-negative bacteria such as those from the Komagataeibacter genus, has emerged as a promising material in biomedical applications due to its exceptional purity, biocompatibility, mechanical strength, versatility in sterilization, biodegradability, and sustainable production. This comprehensive review traces the evolution of BC-based medical products from their initial development in the 1980s to present-day innovations, highlighting the progression of clinical evidence supporting their use. Early clinical studies primarily focused on BC as a temporary skin substitute for burns and ulcers. Over time, the scope of BC applications expanded to include dural defect repair, tympanic membrane reconstruction, and fetal surgery for spina bifida. The quality of clinical evidence has improved, with recent years seeing an increase in randomized controlled trials and larger patient cohorts. Several BC-based products are already commercially available, supported by regulatory approvals and a growing body of clinical data. This review seeks to serve as a valuable resource by providing an exhaustive recapitulation of published clinical studies on BC-based medical devices encompassing 3,857 subjects and offering insights into their efficacy, safety, and regulatory considerations. The review outlines future research directions to validate BC's potential across a wide range of in vivo biomedical applications.

Keywords: bacterial cellulose; clinical investigation; medical device; medical device regulation; nanocomposites.

Figure 1

A) Properties of bacterial cellulose. A wet BC hydrogel is depicted in the center of the figure. B) Trends in scientific and patent publications on the uses of BC for biomedical applications (1990–2023). Search performed in the Scopus and Espacenet databases using the keywords “bacterial cellulose” and its synonyms and the combination of “clinical” or “medical” or “biomedical” or “wound” or “ulcer” or “surgery”.

Figure 2

Distribution of different treatments using BC that have undergone clinical studies from 1987 to 2024 (total: 3857 subjects).

Figure 3

BC‐based medical devices that are mentioned in published clinical studies. Each clinical study is represented by a circle, with the circle diameter proportional to the number of patients. A detailed legend is provided for those studies that included more than 100 patients.

Figure 4

A) Flowchart illustrating the various clinical study designs. The figure does not include cross sectional studies (analytical) and population studies (descriptive), as no studies of these types involving bacterial cellulose were found. B) Adapted quality of evidence pyramid, considering the frequent use of non‐randomized controlled trials and uncontrolled trials in clinical studies involving BC‐based medical devices. C) Distribution of clinical studies by study type for BC‐based medical devices, as expanded in Tables  1 – 4 .

Figure 5

A) Example of a dural closure using a xenograft. Reproduced with permission.^{[ 78 ]} Copyright 2016, Thieme. B) timeline of BC as a dura substitute, from the first in vivo study to commercialization.

Figure 6

A) Illustration of a spina bifida and BC covering the defect. B) timeline of BC to cover spin defects in fetuses, from the first in vivo study to its use in clinical practice.

Figure 7

Summary of uses for BC‐based medical devices.

Figure 8

Clinical development stages according to ISO 14 155:2020 Clinical investigation of medical devices for human.

Figure 9

Medical devices classification rules according to MDR 2017/745.

Figure 10

Rule 19 of the MDR 2017/745 on medical devices incorporating nanomaterials.