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.

Bacterial cellulose has undergone a transformative journey from early applications to its role in advanced regenerative medicine. The review has a pedagogical ambition, offering clear pathways for future research and clinical adoption. Harmonizing regulatory standards and conducting larger, well‐designed clinical trials with standardized endpoints will be essential to fully establish bacterial cellulose's safety and efficacy across diverse medical applications.

1. Introduction

Bacterial cellulose (BC) – also referred to as bacterial nanocellulose, microbial cellulose, microbial nanocellulose, biocellulose, microfibrillar cellulose, biosynthetic cellulose, biosynthesized cellulose, or biosynthesized nanocellulose – is a highly pure form of cellulose produced on an industrial scale using Gram‐negative bacterial cultures. The most efficient producers belong to the Komagataeibacter genus, particularly Komagataeibacter xylinus (synonyms: Gluconacetobacter xylinus and Acetobacter xylinus) and Komagataeibacter hansenii (synonym: Gluconacetobacter hansenii).^{[ 1} , ² , ^{3 ]} First described by Adrian John Brown in 1886,^{[ 4 ]} BC stands out from plant‐derived cellulose because it is free from lignin and hemicelluloses—components that limit the suitability of plant cellulose for biomedical use. In recent years, the synthesis of bacterial cellulose has been extensively reported.^{[ 5} , ⁶ , ^{7 ]}

BC has gained significant attention for its use in the biomedical field due to its exceptional properties, including excellent biocompatibility, high purity, superior water‐holding capacity, mechanical strength, thermal stability, and sustainability, as listed in Figure 1A.^{[ 8 ]} Its nanofibrillated microstructure makes it especially effective for wound dressings, providing a protective barrier against bacterial infections while maintaining a moist environment conducive to healing.^{[ 9 ]} Additionally, BC is compatible with various sterilization methods used in the MedTech industry, such as ethylene oxide treatment, gamma radiation, and autoclaving with moist steam, which enhances its versatility for various applications.

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”.

Despite these advantages, BC lacks intrinsic antibacterial properties, which limits its effectiveness for treating infected wounds. To overcome this, manufacturers commonly employ two strategies: incorporating active antimicrobial agents (like antibiotics or antiseptics) directly into the dressing, or creating composites with antibacterial components such as silver nanoparticles, leveraging BC's thermal stability.^{[ 10} , ^{11 ]} These modifications have spurred significant research and commercial interest, as reflected in the growing number of scientific and patent publications on BC for biomedical use, as illustrated in Figure 1B.

The commercialization of BC‐based medical devices began in the early 1980s when Johnson & Johnson first attempted to bring BC products to market. However, no clinical studies were conducted at that time.^{[ 5 ]} In 1984, Luiz Fernando Xavier Farah discovered that Acetobacter bacteria could produce membranes suitable as skin substitutes, leading to the founding of the Biofill Productos Bioetecnologicos company. The first clinical study using Biofill, a BC‐based dressing, was conducted in Brazil in 1986. Around the same time, Gengiflex, a membrane for post‐dental surgery use, was also introduced. Until the early 2000s, Biofill Productos Bioetecnologicos was the only company commercializing BC membranes as medical devices. Later, Xylos Corporation launched the XCell skin substitute, which was acquired and rebranded by Lohmann & Rauscher as Suprasorb X and Suprasorb X + polyhexamethylene biguanide (PHMB), products that remain on the market today.

Other companies have since entered the field, including Biovico (Poland), S2Medical AB (Sweden), and QRSKIN GmbH (Germany). Additionally, DePuy Synthes, a Johnson & Johnson subsidiary, introduced SyntheCel Dura Replacement in the U.S., offering an alternative to traditional bovine grafts and expanding BC's role in advanced biomedical applications.

This review aimed to provide a comprehensive compilation of clinical studies published in the scientific literature on BC's medical applications, including its use in treating burns, supporting skin grafts, managing ulcers, facilitating implants, and repairing tympanic membrane perforations. Figure  2 illustrates the organization of the studies based on their specific medical applications, revealing that most patients were enrolled in clinical trials focused on burns, skin grafts, and ulcers.

Figure 2.

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

Figure  3 presents a comprehensive compilation of all clinical studies involving BC found in the scientific literature. It highlights an increase in published clinical trials since 2010 and the emergence of BC use in medical implants starting that year.

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.

The review is organized into five sections: analysis of clinical studies by period (1987–2000, 2001–2010, 2011–2019, and 2020–2024), a compilation of commercial BC‐based devices, a critical discussion of ongoing clinical investigations, an explanation of methodological challenges in data collection, and a summary of the regulatory framework for BC‐based devices in Europe.

2. Published Human Studies

In Europe, clinical investigations may be required by the Medical Devices Regulation as part of the clinical evaluation process for the CE certification. They are typically mandated for high‐risk, innovative medical devices or when specific claims must be justified with clinical evidence, for example, to demonstrate superiority over a competitor's device.^{[ 12 ]}

Clinical studies involving therapeutics are usually classified using the Evidence‐Based Medicine Pyramid or the Oxford Levels of Evidence.^{[ 13} , ^{14 ]} While no universally accepted classification scale exists for medical devices, these frameworks can be extrapolated for their evaluation (Figure  4 ).

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 .

Randomized controlled trials (RCTs) and controlled trials are experimental studies with a starting hypothesis that provide high‐quality results by comparing a device to a control. RCTs use randomization to reduce bias. Cohort studies are analytical observational studies that track patients over time, offering real‐world insights but with less control over variables.^{[ 15 ]} Case‐control studies and uncontrolled trials provide moderate quality of evidence, with case‐control studies looking retrospectively at risk factors and uncontrolled trials testing a device without a comparison group. The lowest level of evidence quality comes from case series and case reports, which describe individual or small groups of patients but lack statistical power and control groups.^{[ 16 ]}

Moreover, significant differences in quality can exist between studies of the same type, depending on factors such as the number of patients enrolled, the number of study sites, applicable legislation at the time, and the use of blinding, whether single (participants unaware), double (both participants and researchers unaware), or triple (participants, researchers, and outcome assessors unaware), to minimize bias. However, in some cases, such as open‐label trials, blinding may not be feasible. During the clinical evaluation of a new medical device, each study must be analyzed using specific tools to assess its quality.^{[ 17} , ^{18 ]} As outlined in the tables below, various types of clinical studies and quality of evidence have been identified.

2.1. Before the 2000s

During this timeframe, BC was mainly used as a temporary artificial skin dressing for burns and ulcers, as evidenced by Table 1 summarizing clinical studies from 1987 to 2000. The available literature predominantly consisted of low‐quality evidence, including case studies and case reports, with only a single documented randomized controlled trial.^{[ 19 ]} Biofill and Bioprocess were identical devices made of BC, Bioprocess was commercialized in Europe and Biofill in Brazil. Gengiflex was a thicker patch harvested after 8 days of cultivation instead of 2 days, using double the glucose concentration.^{[ 20 ]} These dry membranes were sterilized using ethylene oxide and had shelf lives of up to 24 months without requiring special storage conditions.

Table 1.

Clinical studies related to BC‐based medical devices (1987–2000). Including the commercial BC product, the number of patients, and the most important outcomes of the study.

Study type	Indication	Treatment	Patients	Outcomes	References
Case report 1987 Brazil	Skin substitute after sternal tumor excision	Biofill	1 adult	No need for dressings, antibiotics, or drugs after 24 h	[21]
Case report 1987 Brazil	3rd‐degree burns	Biofill	1 adult	Reduced pain and healing time; prevented bacterial infection	[22]
Case series 1988 Brazil	Skin‐graft donor areas; mesh‐graft receiving areas; losses of substance through trauma; post‐infection losses of substance; 3rd‐degree burn; post‐debridement defect; post‐tumor resection bloody area; patch‐donor area	Biofill	40 adults	Easy to follow healing due to transparency; best for skin graft donor and recipient areas	[23]
Case series 1988 Brazil	1st to 3rd‐degree burns; surgical wounds; small traumas; skin graft donor site; graft recipient areas	Biofill	60 adults	Reduced pain and hospitalization time; best for 2nd‐degree burns, graft donor sites, and preparing recipient beds for skin grafting	[24]
Case series 1988 Brazil	1st and 2nd‐degree burns; dermabrasion; skin donor sites	Biofill	52 adults	Easy application and follow‐up; surpasses traditional treatments; less expensive; low elasticity	[25]
Case series 1988 Brazil	Dermabrasion; 2nd‐degree burns; skin graft donor sites	Biofill	133 adults	Effective for lesions that are not very deep and areas of little mobility; cheaper than conventional treatment	[26]
Case series 1988 Brazil	2nd‐degree burns; 3rd‐degree burns, skin donor sites; chronic ulcers; dermal abrasion; infectious epidermolysis	Biofill	48 adults	Lacks elasticity; effective temporary skin substitute; easy follow‐up due to transparency	[27]
Case series 1989 Brazil	2nd‐degree burns; 3rd‐degree burns	Biofill	1 child / 1 adult	Reduced pain, fewer dressing changes, asepsis maintained, and reduced need for anesthesia	[28]
Case series 1990 Portugal	2nd‐degree burns; 3rd‐degree burns	Biofill	36 children	Adhesion can be ineffective in 3rd‐degree burns; it reduces infections and hospitalization time	[29]
Case‐control study 1990 Portugal	2nd to 3rd‐degree burns	Biofill vs conventional treatment	26 children	Biofill is more effective and cost‐efficient than conventional treatment	[29]
Case series 1990 Brazil	Trophic ulcers	Biofill	22 adults	Reduced curing time and contamination; more economical than conventional treatment	[30]
Case series 1991 Italy	2nd‐degree burns	Bioprocess	20 children	Excellent adhesion; reduced infections; painless removal and good stimulation of spontaneous re‐epithelialization; lack of elasticity, high cost	[31]
Randomized controlled trial 1992 Italy	Venous stasis ulcer	Bioprocess vs hydrocolloidal medication	135 adults	Bioprocess heals faster and provides better pain relief than comparative treatment	[19]
Uncontrolled trial 1993 Italy	Abrasions; 2nd‐degree burns	Bioprocess	74 adults	The main advantage is pain relief in case of burns; reduction of risks of infection; rapid re‐epithelialization of excellent quality	[32]
Case report 1993 Brazil	Recover periodontal tissues	Gengiflex	1 adult	Complete restoration of the osseous defect around the dental implant	[33]
Controlled trial 1998 Brazil	Recover periodontal tissues	Gengiflex vs Gore‐Tex (ePTFE membrane)	15 adults	Both treatments were effective; no statistical differences	[34]

2.1.1. Treatment of Burns, Ulcers, and Skin Transplants

From the different case reports and case series summarized in Table 1 most of the studies concluded that BC‐based medical devices reduced pain, healing time and hospitalization, prevented infections, allowed easy monitoring due to their transparency, and were more economical than conventional treatments. However, there were also observations on insufficient elasticity or adhesion to the wound when treating third‐degree burns. In 1992, Andreozi et al. conducted the first prospective randomized controlled trial comparing Bioprocess with a commercially available hydrocolloid dressing, not specified, for ulcer treatment in 135 adults. The study concluded that Bioprocess not only promoted faster healing and offered superior pain relief compared to the alternative treatment that was not specified in the original publication.^{[ 19 ]}

2.1.2. Treatment of Periodontal Tissues

In a case report, Gengiflex facilitated the complete restoration of a defect surrounding a dental implant.^{[ 33 ]} In 1998, dos Anjos et al. demonstrated, based on a small controlled trial involving 15 patients, that Gengiflex was as effective as an expanded polytetrafluoroethylene (ePTFE) membrane for treating furcation in mandibular molars.^{[ 35 ]}

2.2. From 2000 to 2010

During this period, only a limited number of clinical studies were reported, with BC primarily used to treat leg ulcers. Table 2 provides a summary of clinical studies conducted. The quality of evidence improved compared to earlier studies; however, the sample sizes in randomized controlled trials remained relatively small.

Table 2.

Clinical studies related to BC‐based medical devices (2001–2010), including the commercial BC product, the number of patients, and the most important outcomes of the study. Dermafill and Bioprocess were identical temporary artificial skin devices made of BC, with Bioprocess commercialized in Europe and Dermafill in the USA. Lohmann & Rauscher acquired XCell, and Suprasorb X is identical to XCell.

Study type	Indication	Treatment	Patients	Outcomes	References
Controlled trial 2004 Poland	Leg ulcer	Bioprocess with elastic bandages vs hydrocolloid Unna boot	93 adults	Application of Bioprocess yields better therapeutic results	[36]
Randomized controlled trial 2004 USA	Leg ulcer	XCell vs non‐adhering dressing (Adaptic) with compression therapy in both cases	24 adults	Significant improvements over Adaptic in autolytic debridement and pain reduction	[37]
Retrospective cohort study 2008 Germany	Chronic ulcers	XCell vs standard moist wound therapy	54 adults	The average reduction in wound size was greater after using XCell than after using the standard dressing.	[38]
Retrospective case series 2009 USA	Leg ulcer	Dermafill	11 adults	Dermafill dressing shortens the time to wound closure over standard care	[39]
Randomized controlled trial 2010 Austria	Leg ulcer	Suprasorb X vs hydrofiber dressing (Aquacel)	40 adults	Both dressings were successful in wound cleansing; pain reduction was better with Suprasorb X.	[40]
Randomized controlled trial 2010	Skin tears	Dermafill vs non‐adherent dressing (Xeroform)	51 adults	Healing time equivalent in both groups; pain control and ease of use were better with Dermafill	[41]

2.2.1. Treatment of Ulcers

In 2004, two prospective comparative studies evaluated the effectiveness of BC in treating leg ulcers. Slezak et al. reported that Bioprocess combined with elastic bandages was more effective than hydrocolloid dressings, while Alvarez et al. found that XCell improved autolytic debridement and reduced pain compared to the non‐adherent dressing Adaptic.^{[ 36} , ^{37 ]} These findings were further supported by retrospective studies conducted at the University Hospital Tübingen in Germany and by Orlando Portal in the USA.^{[ 38} , ^{39 ]} In 2010, Wild et al. reported that Suprasorb X was comparable to the hydrofiber dressing Aquacel in wound cleansing, with BC showing superior pain reduction in a randomized controlled trial.^{[ 40 ]}

2.2.2. Treatment of Skin Tears

A skin tear is a traumatic wound resulting from direct contact between the skin and an object, such as when removing an adhesive dressing or falling against furniture. Elderly individuals are at a higher risk of experiencing skin tears due to the fragility of aging skin.^{[ 42 ]} In 2010, Solway et al. demonstrated, with a randomized controlled trial, that Dermafill was comparable to the standard wound care treatment Xeroform in healing time, while the BC showed superior results in pain reduction and user satisfaction.^{[ 41 ]}

2.3. From 2011 to 2019

Between 2011 and 2019, the application of BC expanded to a larger variety of indications, such as dural defects, male genital surgeries, tympanic membrane perforations, and fetoscopic repair of spina bifida, as detailed in Table 3. These new indications were supported by high‐quality evidence from randomized controlled trials, except for spina bifida, where such trials are considered unethical.

Table 3.

Clinical studies related to BC‐based medical devices (2011–2019), including the commercial BC product, the number of patients, and the most important outcomes of the study.

Study type	Indication	Treatment	Patients	Outcomes	References
Case series 2011 Netherlands	Heel lacerations	Suprasorb X + PHMB	20 children	Good healing time; no infections; pain‐free.	[43]
Randomized controlled trial 2011 USA	Dural defects	SyntheCel Dura Replacement vs bovine tendon collagen vs fetal bovine skin collagen vs synthetic material	99 adults	SyntheCel Dura Replacement is noninferior to other devices; safety and efficacy are equivalent to other devices.	[44]
Randomized controlled trial 2011 Germany	2nd‐degree burns	Suprasorb X + PHMB vs silver‐sulfadiazine cream (Flammazine)	60 adults	Better and faster pain reduction with Suprasorb X + PHMB; cost‐effective.	[45]
Controlled trial 2011 USA	Foot ulcer	Dermafill vs Petrolatum gauze (Xeroform)	30 adults	Dermafill may enhance the rate of wound healing and shorten the epithelialization time.	[46]
Cohort study 2011 Netherlands	Wounds with biofilms	Suprasorb X + PHMB	16 adults	Suitable for moderate to light exuding wounds; reduced pain.	[47]
Case report 2011 Thailand	1st to 3rd‐degree burns	Nanocell	1 adult	Produced moisture, a cooling effect, and pain reduction.	[48]
Randomized controlled trial 2012 Hong Kong	Leg ulcers	4‐layer compression system (Profore) vs short‐stretch compression bandaging system (Rosidal sys) vs moist wound dressing (Suprasorb X; Suprasorb X + PHMB; other dressings)	276 adults	Compression treatments are more effective than moist wound dressing without compression.	[49]
Randomized controlled trial 2012 Austria Switzerland	Critically colonized wounds; locally infected wounds	Suprasorb X + PHMB vs silver dressings	38 adults	Suprasorb X + PHMB was significantly faster and better in removing the critical bacterial load.	[50]
Randomized controlled trial 2012 USA	Leg ulcers	XCell with compression therapy vs non‐adherent dressing (AdapticTM) with compression therapy	38 adults	Autolytic debridement is faster with XCell; no statistically significant difference in healing time.	[51]
Cohort study 2012 Denmark	Surgical wounds	Suprasorb X + PHMB vs hydrophobic dressing (Cutisorb Sorbact)	60 adults	Reduced pain with Suprasorb X + PHMB; easier to remove Suprasorb X + PHMB dressing.	[52]
Randomized controlled trial 2013 Italy	Leg ulcers	Suprasorb X vs foam (both with compression therapy)	46 adults	Suprasorb X significantly improved periwound skin condition.	[53]
Randomized controlled trial 2013 Brazil	Male genital surgery	Non‐commercial BC dressing vs polyurethane dressing (Tegaderm)	60 children	Tolerance of BC is satisfactory and several washes are possible throughout the day.	[54]
Case series 2014 Brazil	Fetoscopic repair of open spina bifida	Bionext with a single continuous stitch	4 fetuses	Surgical closure was successful in 3 cases, resulting in improved hindbrain herniation.	[55]
Case series 2014	Skin graft	Cuticell Epigraft	15 adults	Pain reduction, good aesthetic results.	[56]
Uncontrolled trial 2016 Brazil	Fetoscopic repair of open spina bifida	Bionext with a single continuous stitch	10 fetuses	Two cases were unsuccessful due to loss of uterine access; complete reversal of hindbrain herniation occurred in 6 cases.	[57]
Randomized controlled trial 2016 Brazil	Tympanic membrane perforation	Non‐commercial BC vs autologous temporal fascia	40 adults	Closure time is similar in both groups; operation time is shorter with BC; hospital cost is cheaper with BC.	[58]
Uncontrolled trial 2016 Brazil	Male genital surgery	Non‐commercial BC	129 children; 12 adults	No adverse events; complete healing between the 8th and 10th days after surgery.	[59]
Case report 2016 United Arab Emirates	Skin graft	Nanoskin	1 adult	Promotes the healing process; reduces recovery time.	[60]
Randomized controlled trial 2017 Brazil	Lower limb ulcers	Non‐commercial BC vs dressings with triglyceride oil	25 adults	Advantages of BC are decreased pain and earlier discontinuation of analgesic use.	[61]
Case series 2017 Brazil	Chronic ulcers	Non‐commercial BC loaded with Ibuprofen	14 adults	Favored healing process, pain reduction.	[62]
Uncontrolled trial 2018 Brazil	Fetoscopic repair of extensive open spina bifida	Bionext with a single continuous stitch; Bionext with bilaminar skin substitute (Integra) with 2 stitches	45 fetuses	Antenatal repair can be performed with a bilaminar skin substitute using a percutaneous fetoscopic technique.	[63]
Randomized controlled trial 2018 Egypt	2nd‐degree burns	Epiprotect vs silver sulphadiazine cream (Dermazine)	40 children and adults	Fewer dressing changes with Epiprotect; no significant difference in re‐epithelialization time.	[64]
Case series 2018 Sweden	Nonhealing ulcers	Epiprotect	8 adults	It could decrease the healing time and frequency of dressing changes.	[65]
Randomized controlled study 2018 Thailand	Skin graft donor site	Non‐commercial BC loaded with silk Sericin and PHMB vs Bactigras	21 adults	Same healing time for both groups; scar quality is better with BC.	[66]
Case report 2018 United Arab Emirates	Deep laceration	Nanoskin	1 child	Reduce hospitalization time; complete healing in 3 months.	[67]
Randomized controlled trial 2019 Brazil	Chronic ulcers	Nanoskin vs collagenase dressing (Kollagenase) – both with compression therapy	46 adults	Good results in both groups; no significant differences.	[68]
Randomized controlled trial 2019 Brazil	Chronic ulcers	Non‐commercial BC film and gel vs essential fatty acids and gauze	24 adults	Good results in healing and good tolerance with the cellulose group.	[69]
Case series 2019 Italy	Fetoscopic repair of open spina bifida	Bionext with a single continuous stitch; Bionext with bilaminar skin substitute (Integra) with 2 stitches	5 fetuses	A premature newborn died due to CSF infection and sepsis; neurological outcomes were favorable.	[70]
Case series 2019 Italy	2nd to 3rd‐degree burns	Epiprotect	5 children	Fewer dressing changes; less expensive.	[71]
Retrospective case series 2019 Sweden	1st‐degree burns; excised burns	Epiprotect	38 adults and children	Outcome comparable to porcine xenograft; better pain relief; no cultural issues.	[72]
Case series 2019 Brazil	Pressure ulcers	Non‐commercial BC perforated membranes	10 adults	Worked as a physical barrier; induced tissue remodeling.	[73]
Randomized controlled trial 2019 Egypt	Tympanic membrane perforation	Non‐commercial BC graft vs fat graft vs temporalis fascia graft	120 adults	Shorter time of surgery using BC and better healing.	[74]

2.3.1. Repair of Dural Defects

Following cranial surgery, a graft may be placed before dural closure. While autografts are typically preferred, xenografts (Figure  5 ) or synthetic substitutes may be used when autografts are unavailable.

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.

In 1997, Mello et al. published the first in vivo study on duraplasty using BC as a dura substitute in 32 mongrel dogs. The study demonstrated that BC is a suitable alternative for dura mater in animal models, showing minimal foreign body reactions, no cortical adhesions, and notable malleability.^{[ 75 ]} In 2004, Xylos Corporation filed a patent for the production of a BC‐based dura mater substitute. The patent included findings from an in vivo study in which BC was used as a dura substitute in 8 rabbits. The results showed that the implants were well tolerated, with minimal adhesions observed, leading to the conclusion that BC is an effective dura mater substitute.^{[ 76 ]} To bring the BC‐based dura substitute SyntheCel Dura Replacement to market, DePuy Synthes conducted a controlled clinical investigation between 2006 and 2009, comparing BC to bovine tendon collagen, fetal bovine skin collagen, and synthetic materials in 99 patients. The study concluded that SyntheCel was non‐inferior to these commercially available dural replacement options.^{[ 44 ]} Following this, the company obtained FDA approval for commercialization in 2012.^{[ 77 ]} This information is summarized in Figure 5.

2.3.2. Fetoscopic Repair of Open Spina Bifida

As shown in Figure 6A, spina bifida is a congenital malformation that can result in varying degrees of intellectual impairment, sensorimotor dysfunction, and urinary incontinence, depending on the severity of the condition.

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.

In 2002, Pedreira et al. reported a modified technique to create a spinal defect in 19 fetal rabbits surgically. They used the Biofill patch to cover the defect and obtained a reasonable survival rate compared to other publications.^{[ 79 ]} The following year, they reported three different methods to apply the Biofill patch in 40 rabbit fetuses, confirming that spinal defects can be successfully repaired.^{[ 80 ]} Later, Pedreira et al. developed a new model using fetal sheep.^{[ 81 ]} In 2007, Oliveira et al. used this model to compare the use of human acellular dermal matrix and Biofill patch for repairing spinal defects in 33 fetal sheep. They concluded that Biofill demonstrated superior handling and more effectively prevented neural tissue adhesion.^{[ 82 ]} In 2008, the same group published results of 36 sheep fetuses using the Biofill patch.^{[ 83 ]} In 2011, Pedreira et al. reported using the Bionext patch, composed of BC with a bilaminar artificial skin, to treat more significant spinal defects in seven fetal sheep compared to previous studies. They concluded that the fetus is capable of re‐epithelializing even significant skin defects.^{[ 84 ]} The following year, Herrera et al. compared the traditional neurosurgical three‐layer suture technique with a simplified approach using the Bionext patch to protect the spinal cord, followed by skin closure in 9 pregnant sheep. They concluded that the simplified technique was superior, preserving neural tissue and preventing spinal cord adhesion to the scar.^{[ 85 ]}

These preclinical results led to the first clinical investigation in 2013, involving 10 cases in which a Bionext patch was placed over the lesion with a simple skin closure, instead of the traditional method requiring dissection of the dura mater and multilayer closure. In 2016, Pedreira et al. published the outcomes of the phase I trial in 10 consecutive pregnancies, demonstrating that this approach can achieve a watertight seal, reverse hindbrain herniation, and result in better‐than‐expected motor function.^{[ 55} , ^{57 ]} In 2018, Lapa (Pedreira) et al. published 37 additional cases, demonstrating that antenatal repair of significant open spina bifida defects can be successfully performed using a bilaminar skin substitute over a BC patch with a fully percutaneous fetoscopic technique.^{[ 63 ]} Figure 6B summarizes this information.

2.3.3. Dressing for Male Genital Surgery

In clinical practice, a variety of materials have been utilized following the surgical correction of male genital anomalies. In 2013, Santos Martins et al. compared a multiperforated BC and the polyurethane Tegaderm dressing in a randomized controlled trial involving 60 children. They concluded that the multiperforated BC is a highly satisfactory alternative.^{[ 54 ]} To further validate these findings, de Oliveira Vilar et al. reported results from a before‐and‐after clinical investigation in 2016, which included 141 subjects using the same multiperforated BC without control group. Their study confirmed the efficacy and safety of this wound dressing, highlighting its low cost.^{[ 59 ]}

2.3.4. Tympanic Membrane Perforation

A tear in the tympanic membrane creates an abnormal connection between the external auditory canal and the middle ear. This can result from infection, trauma, or sudden pressure changes.^{[ 86 ]}

Between 2013 and 2014, a randomized controlled trial in Brazil compared BC with the conventional autologous fascia procedure in 40 patients.^{[ 58 ]} The results showed no significant difference in healing time between the two groups; however, the BC group demonstrated shorter operation times and lower costs. In 2019, Mandour et al. further validated the efficacy of BC, showing comparable outcomes to fat and fascia grafts in a randomized controlled trial involving 120 patients, with the added benefit of shorter surgery duration.^{[ 74 ]}

2.3.5. Burns, Ulcers, Skin Transplants, and Other Wounds

As detailed in Section 2.1, BC‐based dressings, such as Biofill and Bioprocess, were used to treat first‐ to second‐degree burns. Piatkowski et al. demonstrated that Suprasorb X + PHMB, a BC dressing incorporating polyhexanide as an antimicrobial agent, provided superior pain management compared to silver sulfadiazine cream in the treatment of partial‐thickness burns in a randomized controlled trial involving 60 subjects.^{[ 45 ]} Additionally, Epiprotect, a BC dressing developed by S2 Medical in Sweden, has been evaluated in three studies, demonstrating efficacy comparable to both silver sulfadiazine cream and porcine xenografts.^{[ 65} , ⁷¹ , ^{72 ]}

Ten studies have documented the use of BC‐based dressings in the treatment of various ulcer types, with findings suggesting that BC dressings offer advantages in pain reduction and wound healing, establishing them as viable alternatives to conventional dressings in ulcer management. However, a study by Wong et al. concluded that compression treatment was superior to standard care without compression. Specifically, they compared a 4‐layer compression system (Profore) to a short‐stretch compression bandaging system (Rosidal sys) and moist wound dressings (including Suprasorb X and Suprasorb X + PHMB) in a randomized controlled trial 276 subjects.^{[ 49 ]}

Beyond ulcers, BC‐based dressings have shown efficacy in treating skin grafts, surgical wounds, heel lacerations, and infected wounds, particularly when combined with PHMB for antimicrobial action.

2.4. From 2020 to 2024

Table 4 presents the most recent large‐scale studies published on the use of BC for fetoscopic repair of spina bifida, treatment of burns in children, management of burns and skin donor graft sites in adults, and dermabrasion procedures.

Table 4.

Clinical studies related to BC‐based medical devices (2020–2024), including the commercial BC product, the number of patients, and the most important outcomes of the study.

Study type	Indication	Treatment	Patients	Outcomes	References
Case series 2020 UK	1st to 3rd−degree burns	Epiprotect	30 children	User‐friendly; well‐tolerated.	[87]
Retrospective cohort study 2020 Germany	2nd to 3rd ‐degree burns	Epicite hydro	56 children	Moderate number of dressing changes; short hospitalization; promotes wound healing.	[88]
Uncontrolled trial 2020 Brazil	Tympanic membrane perforation	Bionext	24 adults	Safe procedure; immediate functional and symptomatic recovery.	[89]
Controlled trial 2020 Brazil	Nail avulsion	Bio‐Nails vs Vaseline with gauze	26 adults	With Bio‐Nails: lower pain intensity, earlier re‐epithelialization.	[90]
Retrospective cohort study 2021 Brazil, USA, Israel, Chile, UK, Italy	Fetoscopic repair of open spina bifida	Bionext with a single continuous stitch; Bionext with bilaminar skin substitute (Integra) with 2 stitches	170 fetuses	Results similar to those reported after hysterotomy‐assisted repair.	[91]
Uncontrolled trial 2021 Austria	2nd‐degree burns	Epicite hydro	16 children	Fewer dressing changes; time to re‐epithelialization similar to frequently used materials.	[92]
Retrospective case‐control study 2021 United Arab Emirates	2nd‐degree burns	Epiprotect vs non‐adherent gauze	28 children	Better pain and parental anxiety in the BC group; healing time was similar in both groups.	[93]
Randomized controlled trial 2021 Brazil	Chronic ulcers	Non‐commercial BC film and gel vs cellulose acetate mesh impregnated with essential fatty acids (Rayon)	39 adults	The healing rate is similar in both groups; there are fewer dressing changes with BC.	[94]
Randomized controlled trial 2021 Iran	Foot ulcer	Non‐commercial BC loaded with venlafaxine and doxycycline vs routine treatment	20 adults	Faster ulcer size reduction with BC; pain‐free walking is better with BC.	[95]
Randomized controlled trial 2022 Sweden	2nd‐degree burns	Epiprotect vs porcine xenograft (EZ Derm)	24 adults	Dressing performed similarly.	[96]
Retrospective cohort study 2022 Germany	1st‐ to 3rd‐degree burns	Epicite hydro vs polyurethane foam dressing	190 children	No significant difference in wound healing; shorter hospitalization time with BC.	[97]
Retrospective case series 2022 Germany	Chronic wounds	Epicite hydro	44 adults	Fibrous tissue reduction; wound size reduction.	[98]
Randomized controlled trial 2022 Austria	Skin graft donor sites	Epicite hydro vs ibuprofen‐containing foam (Biatain Ibu) vs silver‐impregnated foam (Mepilex Ag)	46 adults	Better pain relief with Biatain Ibu; user friendliness in favor of BC; no difference in wound healing between groups	[99]
Retrospective case‐control study 2022 France	2nd‐degree burns	Epicite hydro vs daily exposure to an infrared lamp after thorough cleaning and antiseptic treatment of the burn	60 children	There is no difference in wound healing between groups; there is a reduction in hospital length and pain experience with BC.	[100]
Uncontrolled trial 2022 Germany	2nd‐degree burns	Epicite hydro vs synthetic dressing (Suprathel)	20 adults	Similar outcome for both groups	[101]
Randomized controlled trial 2022 China	1st‐ to 2nd‐degree burns; skin graft donor sites	Non‐commercial BC vs Vaseline gauze	207 adults	Healing time is shorter with BC for 1st‐degree burns and equivalent for other indications.	[102]
Controlled trial 2022 China	Carotid artery stenosis	Non‐commercial BC‐heparin stent vs conventional treatment	98 adults	Fewer postoperative complications with BC‐heparin stent; nursing satisfaction is better with BC‐heparin.	[103]
Randomized controlled trial 2022 Brazil	Cutaneous leishmaniasis	Nexfill Biocellulose Curatives with meglumine antimoniate (Glucantime) vs Glucantime alone	20 adults	Higher cure rate at 60 days with BC.	[104]
Case series 2023 Brazil	Fetoscopic repair of open spina bifida in twin pregnancy	Bionext sutured with or without a myofascial flap	14 fetuses	Feasible technique; low risk to twins and mother when performed by an experienced team.	[105]
Randomized controlled trial 2023 Thailand	Epidermal ablative wound healing from a CO2 laser	Non‐commercial BC vs petrolatum gauze	26 adults	Comparable efficacy in both groups.	[106]
Randomized controlled trial 2024 Brazil	Cutaneous leishmaniasis	Nexfill Biocellulose Curatives with meglumine antimoniate (Glucantime) vs autoclaved gauze with Glucantime vs Glucantime	69 adults	Use of BC and autoclaved gauze improves outcomes.	[107]
Retrospective cohort study 2024 China	Treatment after dermabrasion surgery	Nanomei vs allogenic skin	317 children	Shorter healing time with BC; fewer dressing changes with BC.	[108]
Uncontrolled trial 2024 Brazil	Chronic ulcers	Nexfill	17 adults	Safe; facilitates partial or complete healing.	[109]

2.4.1. Fetoscopic Repair of Spina Bifida

In 2021, Lapa et al. published a retrospective study involving 170 cases of prenatal spina bifida repair. They concluded that their method – percutaneous fetoscopy using a BC patch placed between the neural placode and the skin/myofascial flap without suturing the dura mater – achieved long‐term neurological outcomes comparable to those observed in children who underwent the traditional, more invasive hysterotomy‐assisted repair, which involved a large uterine incision.^{[ 91 ]} In 2023, this less‐invasive technique was reported with the successful fetoscopic repair of open spina bifida in twin pregnancies.^{[ 105 ]}

2.4.2. Burns

The use of Epiprotect and Epicite hydro has been reported in six studies involving pediatric patients. These studies demonstrated that BC dressings were comparable to standard treatments in wound healing, with the added benefits of reducing hospital stay and alleviating pain due to its moist environment and active wound debridement. Similar results were reported in four studies involving adults. Furthermore, in 2024, Zhao et al. reported on the use of Nanuomei, the first BC product introduced to the Chinese market, for post‐dermabrasion treatment following eschar removal in pediatric scald injuries. They concluded that BC dressings offered shorter healing times and reduced the frequency of postoperative dressing changes, making them particularly suitable for pediatric burn care.^{[ 108 ]}

2.4.3. Ulcers

It has been reported that BC is as effective as cellulose acetate mesh impregnated with essential fatty acids (Rayon) for treating chronic ulcers. It also reduces the frequency of dressing changes in a randomized controlled trial with 39 subjects.^{[ 94 ]} Additionally, BC loaded with venlafaxine, an antidepressant recently explored for pain management, and the antibiotic doxycycline demonstrated pain reduction in patients with foot ulcers in a small randomized controlled trial involving 20 subjects.^{[ 95 ]}

2.4.4. Cutaneous Leishmaniasis

Cutaneous leishmaniasis is a skin infection transmitted by the bite of an infected sand fly. The infection initially presents as nodules, which may progress into large, chronic ulcers if left untreated. In two recent randomized controlled trials, it has been shown that combining BC with meglumine antimoniate can improve the chemotherapy outcome in cutaneous leishmaniasis caused by L. braziliensis.^{[ 104} , ^{107 ]}

Carotid artery stenosis occurs when a substance called plaque builds up, blocking the normal flow of blood in the artery and causing a stroke. In 2022, Wan et al. reported on the combined use of BC and heparin, a blood anticoagulant, in carotid artery stent implantation, involving 98 patients. Their findings indicate that the BC‐heparin combination significantly reduced postoperative complications and enhanced nursing satisfaction compared to the conventional procedure.^{[ 103 ]}

3. Overview of BC‐Based Medical Devices

Table  5 presents a compilation of various commercialized BC‐based medical devices and the companies engaged in their clinical research and development.

Table 5.

Overview of the companies that have sold or sell bacterial cellulose‐based medical devices.

Company	Product	Intended purpose	References
Fibrocel Produtos Biotechnologies LTDA (previously BioFill Productos Biotecnologicos) Brazil	Biofill (not available) Bioprocess (not available) Dermafill (not available)	Wounds, ulcers, burns, skin tears, skin donor sites.	[110]
	Gengiflex (not available)	Recovery of periodontal tissues.	[33]
Xylos corporation USA	XCell Wound Dressing (not available) XCell Antimicrobial Wound Dressing (not available)	Wounds, ulcers, burns, surgical wounds, skin donor sites, dermal lesions.	[111, 112]
	Xylos Surgical Mesh (not available) Xylos Porous Surgical Mesh (not available)	Implantation to reinforce soft tissues, i.e., abdominal and thoracic wall defects.	[113, 114]
	Securian Tissue Reinforcement Matrix (not available) MTA Surgical Sheet (not available)	Management and protection of soft tissue and tendon injuries.	[115, 116]
	Xylos Vessel Guard (not available)	Cover for vessels during anterior vertebral surgery.	[117]
Axcelon Biopolymers Corp Canada	Nanoderm (availability unknown)	Burns and wounds.	[118]
Gana R&D Korea	Gana Patch (availability unknown)	Unknown.	[119]
Tigerplast Thailand	Innaqua (availability unknown)	Unknown.	[120]
PatchMed Philippines	Cocopatch (availability unknown)	Burns, bedsores, diabetic wounds.	[121]
Ardor Biomed India	Cocoheal (available in India) Cocoheal Ag+ (availability unknown)	Wounds, burns, ulcers, surgical wounds, skin donor sites.	[122]
Bionext Produtos Biotecnológicos Ltda Brazil	Bionext (availability unknown) Bionext XP (availability unknown)	Burns; ulcers; surgical wounds.	[123]
Innovatec's Pesquisa e Desenvolvimento Biotecnologico Ltda Brazil	Nanoskin (availability unknown)	Wounds; ulcers; burns; skin donor sites; surgical wounds.	[124]
Seven Biotecnologia Brazil	Nexfill Curative (availability unknown) Nexfill Porous curative (availability unknown) Nexfill Hydrogel (availability unknown)	Ulcers and burns.	[125]
Biovico (previously BOWIL Biotech) Poland	Celmat Wound (available in the EU) Celmat Wound H (available in the EU)	Wounds and burns.	[126]
Lohmann & Rauscher Germany and Austria	Suprasorb X (available in EU) Suprasorb X + PHMB (available in EU)	Wounds; burns; ulcers; surgical wounds; skin donor sites	[127]
DePuy Synthes USA	SyntheCel Dura Replacement (available in the US)	Dura replacement is used to repair the dura mater in adults.	[128]
S2Medical AB Sweden	Epiprotect (available in the EU)	Burns and ulcers	[129]
QRSKIN GmbH Germany	Epicite hydro (available in the EU)	Wounds, burns, skin donor sites, and surgical wounds.	[130]
Vuelo Pharma Ltda Brazil	Membracel (available in Brazil)	Burns, ulcers, surgical wounds, and skin donor sites.	[131]
Essity AB Sweden	Cuticell Epigraft (available in EU)	Wounds, burns, and skin donor sites.	[132]
Coreleader Biotech Taiwan	Bio‐skinG (availability unknown)	Wounds, burns, ulcers, and skin donor sites.	[133]
Hylomorph Switzerland	Startup R&D: Hylomate pouch (in clinical investigations)	Separation layer between the body tissue and a cardiac implantable electronic device (pacemaker or defibrillator).	[134]
AxCell Laboratories Canada	Startup R&D	Unknown	[135]
BioSmart Nanotechnology Ltda Brazil	R&D company	Used in a clinical study to treat chronic ulcers.	[136]

Fibrocel Produtos Biotechnologies LTDA was the first company to report the clinical investigation and commercialization of BC‐based wound dressings.^{[ 137 ]} In 1998, Xylos Corporation received FDA approval for XCell Wound Dressing, asserting its substantial equivalence to Johnson & Johnson's NU‐GEL hydrogel wound dressing, made of polyvinylpyrrolidone, and ConvaTec's Aquacel dressing, composed of sodium carboxymethylcellulose.^{[ 114 ]} Neither of those dressings is available on the market.

Several BC‐based wound dressings, including Nanoderm, Gana Patch, Innaqua, Cocopatch, and Cocoheal, have been developed.^{[ 118} , ¹¹⁹ , ¹²⁰ , ¹²¹ , ^{122 ]} However, no clinical studies have been published for these products, and they are currently unavailable in the European market. As discussed in Section 3, Nexfill and Bionext have been evaluated in clinical studies and are potentially accessible solely within the Brazilian market.^{[ 55} , ⁵⁷ , ⁶³ , ⁷⁰ , ⁸⁹ , ⁹¹ , ¹⁰⁴ , ¹⁰⁵ , ¹⁰⁷ , ^{109 ]}

According to available manufacturer information, Celmat, Suprasorb X, SyntheCel Dura Replacement, Epiprotect, Epicite hydro, Membracel, Cuticell Epigraft are currently commercially available products.^{[ 126} , ¹²⁷ , ¹²⁸ , ¹²⁹ , ¹³⁰ , ¹³¹ , ^{132 ]} Figure  7 provides an overview of the various BC‐based medical devices and their indications.

Figure 7.

Summary of uses for BC‐based medical devices.

4. Ongoing Human Studies

Hylomorph (Simone Bottan, Aldo Ferrari, Francesco Robotti), a spin‐off from ETH Zurich, has developed the Hylomate Pouch, a medical device made from micro‐engineered BC that is produced using a microstructured mold positioned at the liquid‐air interface during biosynthesis, creating 2 µm‐deep micro‐wells with diameters under 5 µm. This innovation is designed to help surgeons reduce foreign body reactions and fibrosis following the pacemaker implantation procedure.^{[ 138 ]} In 2020, Hylomorph published in vivo results demonstrating that using micro‐engineered BC led to a 66% reduction in fibrotic tissue thickness surrounding the implanted pacemakers in 16 minipigs. Based on these encouraging findings, a clinical investigation (DRKS‐ID: DRKS00019951) was initiated in 2019, enrolling 46 subjects. This study is expected to be completed in 2027. Preliminary results indicate positive outcomes, with surgeons rating the handling and removal of Hylomate as “easy”. The device has shown a low complication rate, consistent with existing data on BC membranes, and no device‐related adverse events have been reported.^{[ 139 ]}

Additionally, in 2019, the University of the Philippines initiated a clinical investigation (NCT Number: NCT05079763) to evaluate the efficacy of BC‐monolaurin hydrogel compared to a placebo cream in treating acute radiation dermatitis. The study's completion date remains unknown, and no results have been published.

In 2023, UPM Biomedicals launched a controlled clinical trial (NCT Number: NCT05629091) comparing their FibDex wound dressing, made from wood‐based nanocellulose, to Epicite Hydro and Epiprotect for treating superficial dermal burns in pediatric and adult patients.

Similarly, in 2023, Karaj University of Medical Sciences in Iran started a controlled clinical study (Registration Number: IRCT20160117026069N6) to assess the effectiveness of BC versus conventional ointment dressings for managing second‐degree burns. The results have yet to be published.

The same year, Shiraz University of Medical Sciences in Iran commenced a controlled clinical study (Registration Number: IRCT20181121041713N5) in orthodontics, comparing BC‐coated elastomeric ligatures with conventional ligatures. Results are still pending.

Lastly, in 2024, Revision Skincare launched a clinical trial (NCT Number: NCT06633731) to evaluate the efficacy and tolerability of a topical facial treatment regimen that includes a facial treatment, bio‐cellulose mask, and post‐procedure cream. The results are forthcoming.

5. Limitations of the Review

5.1. Finding Clinical Studies

Only a limited number of studies are currently registered in the clinicaltrials.gov database. In Europe, a comparable platform, the European Database on Medical Devices (EUDAMED), is under development. Once operational, EUDAMED will serve as a centralized registry for clinical investigations involving medical devices, facilitating access to clinical data. For this review, clinical publications were identified using the Scopus search engine by combining “bacterial cellulose” with relevant synonyms and medical terms. Several publications related to the BC‐based device Biofill were additionally retrieved from the medical articles section on the Dermafill website (www.dermafill.com). Similarly, ongoing human studies were identified through the International Clinical Trials Registry Platform (ICTRP) search engine (https://trialsearch.who.int/) using the same set of search terms.

5.2. Unavailable Scientific Publications

Several scientific articles on clinical studies involving BC were identified but could not be accessed.^{[ 140} , ¹⁴¹ , ¹⁴² , ¹⁴³ , ¹⁴⁴ , ¹⁴⁵ , ¹⁴⁶ , ^{147 ]}

6. Regulatory Aspects in Europe

In Europe, the introduction of the new European Medical Device Regulation (MDR) 2017/745 represents a stringent framework for developing clinical investigations on medical devices. Sponsors are advised to follow the ISO 14 155:2020 standard, which provides guidelines for the clinical investigation of medical devices in humans. Clinical development stages according to this standard are presented in Figure  8 .

Figure 8.

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

Once an Ethics Committee approves the study protocol, authorization from the national competent authority, such as the Spanish Agency of Medicines and Medical Devices in Spain, may be required. This requirement applies unless the device already has CE marking and is being used within its approved intended purpose and instructions.

6.1. What is a Medical Device?

A medical device is any product that interacts directly with patients to diagnose, prevent, monitor, treat, or alleviate diseases or injuries. Examples include pacemakers, wound dressings, intraocular lenses, surgical instruments, and wheelchairs. The European Medical Device Regulation (MDR) 2017/745 provides a detailed definition.

Defining the intended purpose is essential for classifying the device into one of four categories: Class I, IIa, IIb, or III (see Figure  9 , Annex VIII of the MDR 2017/745 and guidance documents^{[ 148} , ¹⁴⁹ , ^{150 ]}). The risk associated with the device increases with the class number, while the higher the classification, the more complex the process to obtain the CE mark will be.

Figure 9.

Medical devices classification rules according to MDR 2017/745.

For example, the BC‐based implant SyntheCel Dura Replacement is classified as class III under rule 8 as it is used in direct contact with the central nervous system (dura mater). BC‐based wound dressings, such as Suprasorb X, are classified as Class IIb under rule 4, as they are intended for skin injuries that have breached the dermis and require healing by secondary intention.

6.2. BC‐Based Devices: Borderline Devices and Rule 14

Borderline products are those for which it is not clear whether the legislation on medical devices or other legislation applies, such as medicines,^{[ 151} , ^{152 ]} cosmetics,^{[ 153 ]} in vitro diagnostic medical devices,^{[ 154 ]} and biocidal products.^{[ 155 ]}

According to rule 14 of the MDR 2017/745, all devices incorporating, as an integral part, a substance which, if used separately, can be considered to be a medicinal product […] and that has an action ancillary to that of the devices, are classified as class III. For example, Suprasorb X + PHMB is classified as Class III under rule 14, since polyhexanide (PHMB) is considered a medicinal product with an ancillary antimicrobial action.

6.3. BC‐Based Medical Device Incorporating Nanoparticles (NPs)

As defined in the MDR 2017/745, nanomaterial means a natural, incidental or manufactured material containing particles in an unbound state or as an aggregate or as an agglomerate and where, for 50% or more of the particles in the number size distribution, one or more external dimensions is in the size range 1–100 nm. Examples include iron oxide‐based nanomaterials, such as NanoTherm nanoparticles (MagForce NT GmbH), used in brain tumor treatment, and silver nanoparticles, incorporated into various medical devices across fields like wound care, urology, nephrology, cardiology, and anesthesiology.^{[ 156} , ^{157 ]}

If a BC‐based medical device contains nanoparticles (NPs), rule 14 may apply if the NPs are considered medicinal products. Otherwise, rule 19 of the MDR 2017/745 will be applied as illustrated in Figure  10 . The primary risk is associated with the potential release of free nanoparticles from the device and the duration of exposure.^{[ 149 ]} The Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) has published guidance to aid manufacturers in evaluating exposure potential, toxicokinetics, and the toxicological profile of their devices using in vitro and in vivo models.^{[ 158 ]} The SCENIHR also published a guidance document for silver NPs.^{[ 159 ]}

Figure 10.

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

7. Conclusion and Perspectives

BC has undergone a transformative journey from its early applications as a temporary skin substitute to its current role in advanced regenerative medicine. Over four decades of clinical research have demonstrated its efficacy in diverse areas, including burn care, ulcer management, dural defect repair, and fetal surgery for spina bifida. While BC's unique properties, such as high purity, biocompatibility, sustainable production, and biodegradability, have driven its adoption, several limitations persist. For instance, the lack of intrinsic antibacterial activity remains a limitation, necessitating composite formulations with antimicrobial agents to enhance functionality. Besides, BC use in third‐degree burns and highly exudative wounds can result in suboptimal adhesion. In addition, while recent randomized controlled trials have strengthened the evidence base, many studies still involve small cohorts or single‐center designs, limiting generalizability. Moreover, innovations like fetoscopic spina bifida repair rely heavily on animal models due to ethical barriers to human trials, creating gaps in translational evidence.

The next wave of BC development will likely focus on multifunctional composites that combine antimicrobial, regenerative, and even innovative drug‐delivery capabilities. At the same time, advances in material engineering, such as 3D bioprinting and customizing BC's mechanical and structural properties, may expand its utility to load‐bearing tissues, organ repair, and other high‐value medical specialties. Efforts to optimize bacterial strains and utilize more sustainable feedstocks could further reduce production costs. Furthermore, harmonizing regulatory standards and conducting larger, well‐designed clinical trials with standardized endpoints (e.g., wound closure rates, infection recurrence) will be essential to fully establish BC's safety and efficacy across diverse medical applications. Finally, a promising emerging trend concerns the integration of BC with digital health and monitoring by incorporating biosensors or digital health components into BC dressings, enabling real‐time monitoring of wound healing or infection status, and supporting personalized medicine approaches. As BC transitions from niche applications to mainstream medical use, addressing these challenges will require collaboration between microbiologists, material scientists, and clinicians.

Conflict of Interest

The authors declare no conflict of interest.

Biographies

Thomas Meslier is a Contracted Researcher at the Institute of Materials Science of Barcelona (ICMAB‐CSIC). He develops medical devices from bacterial cellulose for ophthalmologic applications in collaboration with the Centro de Oftalmología Barraquer. His work also includes preparing clinical investigation documents, supporting clinical studies, drafting reports, and addressing medical regulatory aspects of these devices.

Justin Christopher D'Antin is a researcher & Eye bank specialist at Centro de Oftalmología Barraquer. He has a PhD in cellular biology from the Autonomous University of Barcelona (UAB), based on lens capsule tissue culture for the investigation and prevention of Posterior Capsule Opacification. He previously obtained his Master's degree in biomedicine at the University of Barcelona.

Gemma Julio is the Deputy Director of Research at the Centro de Oftalmología Barraquer in Barcelona, Spain. She specializes in the methodology of clinical research in different ophthalmology areas. Her department collaborates with several universities and research centers, highlighting the collaboration with the Institute of Materials Science of Barcelona (ICMAB‐CSIC).

Anna Roig is a Research Professor at the Institute of Materials Science of Barcelona (ICMAB‐CSIC), where she leads the Nanoparticles and Nanocomposites Group (nn.icmab.es). Her research pivots around the rational synthesis of nanomaterials using green chemistry and biotechnology approaches and their validation in biomedical uses. Specifically, her group has developed nanomaterials as drug delivery nanocarriers, contrast agents, or bacterial cellulose as patches for hernia, cryopreserving cell constructs, and ophthalmologic uses.

Meslier T., D'Antin J. C., Julio G., and Roig A., “A Comprehensive Review of Clinical Studies on Bacterial Cellulose: From the Earliest Uses to Contemporary Innovations.” Adv. Healthcare Mater. 14, no. 27 (2025): e02189. 10.1002/adhm.202502189