Three-dimensional Bovine Collagen–Elastin Matrix in Soft Tissue Reconstruction: No Detectable Bovine DNA After 1 Year

Abstract

Background:

Postoperative wound healing remains a critical challenge, particularly in complex reconstructions such as free flap surgeries. Despite technical improvements, perfusion-related complications may cause partial flap loss. Following wound stabilization, secondary measures such as vacuum-assisted closure therapy and skin grafting are required. Three-dimensional bovine collagen–elastin matrices offer promising support by enhancing cell migration, angiogenesis, and tissue regeneration.

Methods:

We report the case of a 43-year-old woman who developed partial necrosis after deep inferior epigastric perforator flap reconstruction. She was treated with vacuum-assisted closure therapy, followed by the application of MatriDerm 1 mm and split-thickness skin grafting. After 12 months, histological analysis and quantitative reverse transcription polymerase chain reaction (PCR) were performed on the grafted area to assess tissue integration and detect residual bovine DNA.

Results:

Histology showed full regeneration of the epidermis and dermis without detectable bovine matrix remnants. No elastic fibers from MatriDerm were visible, and quantitative reverse transcription PCR confirmed the absence of bovine DNA, despite ongoing tissue remodeling and macrophage infiltration.

Conclusions:

These findings demonstrate complete resorption and integration of a 3-dimensional bovine collagen–elastin matrix within 1 year, without immunologically relevant residues. Compared with other dermal substitutes such as Integra, MatriDerm shows faster degradation and a lower risk of foreign body reactions. The observed tissue remodeling indicates a prolonged regenerative process depending on wound type and depth. MatriDerm is a safe and effective dermal matrix, ensuring complete resorption and tissue integration. The absence of bovine DNA supports its immunologic safety and clinical suitability for complex wound treatment requiring durable and aesthetic outcomes.

Takeaways

Question: Is there a residual bovine matrix after 1 year?

Findings: No bovine DNA is detectable after 1 year.

Meaning: MatriDerm is fully integrated after 1 year.

INTRODUCTION

Postoperative wound healing is a central aspect of medical care, especially for patients with impaired or delayed healing. Complex reconstructive procedures such as free flap surgeries are crucial for restoring form and function in cases of large soft tissue defects or body contour reconstruction and represent the most advanced tier of the reconstructive ladder or elevator.^1,2 Nevertheless, perfusion-related complications can occur during these procedures, such as arterial or venous disturbances, which may lead to necrosis or partial necrosis of the free tissue transplant. For example, in the case of the deep inferior epigastric perforator flap used for breast reconstruction, a German multicenter study from 2021 reported a rate of total flap loss of 2.0%, whereas emergency vascular revisions were necessary in 4.3% of cases.³ Although rare, such complications require complex management, often involving multiple revision procedures.

Once stable wound conditions are achieved after the acute phase, secondary wound conditioning—such as with vacuum therapy (vacuum-assisted closure [VAC])—can be performed to enable later defect coverage with full-thickness or split-thickness skin grafts. A promising adjunct to wound healing in such scenarios is the use of collagen–elastin matrices (CEMs), such as MatriDerm (MedSkin Solutions Dr. Suwelack AG, Germany). This matrix was developed to function as a dermal substitute. In Germany, the costs for MatriDerm as a xenogeneic skin substitute are covered by statutory health insurance . The procedure is billed using the OPS codes 5-916.2 for xenogeneic skin substitutes. Therefore, patients typically incur no additional costs, as both the material and procedure are covered within hospital budgets or diagnosis-related group-based reimbursement. In cases treated at our institution, including the present one, the material cost of MatriDerm accounts for less than 1% of the total treatment costs.

MatriDerm is a dermal substitute composed of bovine collagen (types I, III, and V) as well as elastin hydrolysate.⁴ It features a porous structure that permits immediate skin grafting onto the 1- or 2-mm thick material. In doing so, it supports cell migration, particularly of fibroblasts and keratinocytes, promotes angiogenesis, and can thus facilitate the regeneration of functional tissue.⁵ The use of MatriDerm is of particular clinical interest in the treatment of deep, complex wounds with exposed tendons or bone, as conventional skin grafts are often insufficient under such conditions.^6,7 Contraindications include known hypersensitivity or allergy to bovine collagen or matrix components, active systemic infection or uncontrolled local wound infection, inadequate wound bed preparation or hemostasis, and patient noncompliance that would prevent proper postoperative care. Due to its bovine-derived components, MatriDerm may also be contraindicated for patients who avoid animal products for religious or cultural reasons. Alternatively, other CEMs such as Integra (Integra LifeSciences Corporation, Plainsboro, NJ) can also be used. However, the authors prefer the use of MatriDerm due to the possibility of single-stage application.

Numerous studies have already addressed various aspects of MatriDerm application, including optimization of layer thickness, combinations with vacuum therapy, or the functional and aesthetic outcomes following defect coverage.^8,9 In cases of infected wounds or in patients with relevant comorbidities, MatriDerm should be applied in a 2-stage procedure. This approach allows for optimal wound bed conditioning and reduces the risk of matrix failure or infection recurrence.⁹

For example, Dickson et al¹⁰ demonstrated that within the first 2 weeks after MatriDerm application, early vascularization as well as an inflammatory cell infiltrate could be detected, as would be expected in the context of wound healing. The same study also showed that MatriDerm was resorbed more quickly than other dermal substitute materials, with initial signs of resorption appearing in week 3 following split-thickness skin grafting. A complete replacement of MatriDerm by a neodermis occurred after 2 months.¹⁰ However, the presence of bovine DNA in this case was not investigated.

To date, systematic histological analyses of the long-term integration of MatriDerm into human tissue after complete healing are rare in the literature. In particular, it remains unclear to what extent components of the original bovine CEM—such as residual DNA—can still be detected months to years later and how they are integrated into or broken down by the body’s own tissue structure. This study therefore presents the first histological examination of matrix integration during a period of 1 year postimplantation, specifically analyzing the cellular and structural composition of the newly formed tissue at the former graft site as well as the presence of bovine DNA using qRT-PCR.

METHODS

We present the case of a 43-year-old female patient who, due to a left-sided Baker grade IV capsular contracture following mastectomy for invasive lobular breast carcinoma, underwent autologous breast reconstruction using a deep inferior epigastric artery perforator flap (Fig. 1). During the postoperative course, the patient developed a venous outflow problem resulting in partial necrosis of the medial pole of the flap (Fig. 2). Following resection of the necrotic tissue and radical debridement, we initiated VAC therapy, with subsequent application of MatriDerm Flex 1 mm after 17 days (Fig. 2). The ribs were not exposed. The VAC dressing was changed every 5–7 days. At each VAC dressing change, perfusion of the wound bed was assessed using indocyanine green angiography. MatriDerm was applied after 17 days because a well-perfused wound bed was not observed uniformly across the entire defect area. Upon complete integration of the CEM and well-perfused, heterogenous indocyanine green signal of the wound bed, a split-thickness skin graft (mesh ratio 1:1.5, 0.2-mm thickness) was harvested from the left thigh and applied (Fig. 3). During contralateral balancing mastectomy with mastopexy after 4 months, the split-thickness skin graft area was excised to redefine the left inframammary fold (Fig. 4).

Fig. 1.

Intra- and postoperative situs of a 43-year-old patient with capsular contracture. A, Preoperative markings. B, Postoperative view following left DIEP flap breast reconstruction. C, Partial necrosis of the medial pole of the DIEP flap. DIEP, deep inferior epigastric perforator.

Fig. 2.

Intraoperative situs and MatriDerm application. A, Lateral view before debridement. B, Incomplete granulation during VAC therapy in the absence of MatriDerm. C, Application of 1 mm MatriDerm.

Fig. 3.

Split-thickness skin graft intra- and postoperative.A, Application of split-thickness skin graft (0.2mm thickness). B, Fully integrated split-thickness skin graft after 6 months. C, Positive pinch test 6 months after split-thickness skin graft.

Fig. 4.

Six months after scar resection, resection of the skin island and symmetrizing breast reduction of the opposite side with mastopexy. A, Anterior view. B, 45° view right side. C, Right-sided view. D, Left-sided view.

The excised specimen—comprising both normal skin and a split-thickness graft with integrated MatriDerm—was sent for further diagnostic evaluation.

Detection of Bovine DNA Using qRT-PCR

Paraffin-embedded tissue specimens of healthy skin and split-thickness skin with dermally integrated MatriDerm were cut into 50-µm-thick slices. To extract DNA, 3 slices per sample (healthy skin and grafted skin with integrated MatriDerm) were treated according to the protocol of the ReliaPrep FFPE gDNA Miniprep System (Promega) with native MatriDerm serving as a positive control. The isolated DNA of samples and MatriDerm was then further processed using the foodproof SL Bovine Species Detection Kit (Hygiena Diagnostics GmbH, Germany) according to the manufacturer’s instructions. Thereby, a positive signal (fluorescence accumulation curve crosses the threshold line) is considered with the presence of bovine DNA.

RESULTS

Histological Examination

The normal skin consists of the narrow epidermis (a), the fiber-rich dermis (b), and the fat-rich subcutis (c). In the case of chronic wound healing disorder, an ulceration occurred with the loss of the epidermis (a) as well as severe inflammation in the dermis (b) and subcutis (c), including fat tissue necrosis (asterisks) and, over the course of chronic inflammation, increased fibrosis (X). (See figure, Supplemental Digital Content 1, which displays the hematoxylin–eosin staining of split-thickness skin graft areas with and without MatriDerm. A, split-thickness skin graft; B, original subcutis; a, epidermis; b, dermis; c, subcutis; >>, estimated MatriDerm layer; X, fibrosis; *, fat tissue, https://links.lww.com/PRSGO/E786.)

In the mesh-grafted area, the damaged layers were replaced. The MatriDerm dressing on the wound defect is thus expected to be positioned above the original fat tissue necrosis of the underlying subcutaneous connective tissue (B) and beneath the new dermis (>>>) (Supplemental Digital Content 1, https://links.lww.com/PRSGO/E786).

In the enlarged sections (rectangle in Supplemental Digital Content 2), this area was examined using several special stains. (See figure, Supplemental Digital Content 2, which displays the Elastica–Van Gieson and CD68 PGM1 staining. Open arrows, elastic fibers in vessels; closed arrows, expected bovine elastic fibers in MatriDerm; +, macrophages [brown], https://links.lww.com/PRSGO/E787.) In the Elastica–Van Gieson stain, elastic fibers are shown in black. The elastic fibers in the blood vessels of the graft are clearly visible.

Because MatriDerm contains bovine collagen fibers, a similar presentation using the Elastica–Van Gieson stain would have been expected. However, no elastic fibers are detectable in the area of the MatriDerm dressing (closed arrows in Supplemental Digital Content 2, https://links.lww.com/PRSGO/E787). Here, increased fibrosis (pink fibers) is observed.

Detection of Bovine DNA by qRT-PCR

Although bovine DNA could be detected in the MatriDerm positive control, no bovine DNA was found in any of the skin samples (healthy or skin graft). (See figure, Supplemental Digital Content 3, which displays the results of the qRT-PCR analysis for detection of bovine DNA. A, Amplification plot of controls and patient samples. B, Overview of c_t values [threshold = 0.3; n.d. = not detectable], https://links.lww.com/PRSGO/E788.)

DISCUSSION

The use of MatriDerm for the reconstruction of various soft tissue defects has been extensively described in the literature.^10–12 Regarding long-term outcomes, it has been shown that, compared with other dermal substitute materials such as Integra (Integra LifeScience Corporation), MatriDerm is associated with fewer foreign body reactions but a higher risk of scar contractures.¹⁰ However, our case demonstrated that after wound conditioning via VAC therapy and subsequent MatriDerm application, a highly elastic and noncontractured split-thickness skin graft area was present at the 12-month follow-up. The more frequent observation of scar contractures in previous studies using MatriDerm may be attributable to the underlying burn injuries in those cohorts.^13,14

In a histological study by Dickson et al,¹⁰ the integration of MatriDerm was analyzed in biopsies taken several weeks and months after application.¹⁰ The results of that study support our findings, in which we likewise found no detectable bovine DNA. However, in our long-term data, macrophage infiltration was still observed, indicating a prolonged remodeling process in the area affected by postoperative necrosis. Contrary to the findings of Dickson et al,¹⁰ this suggests that, in our case, tissue remodeling persisted for a longer period, possibly due to differences in etiology (burn injury versus postoperative wound healing disorder), thereby limiting the comparability of the 2 studies.

In our study, no bovine DNA from the original MatriDerm matrix could be detected, highlighting the distinctive properties of the product and its unique resorption process despite ongoing tissue remodeling. MatriDerm is composed of a noncrosslinked CEM specifically designed to promote rapid cellular infiltration and to support the wound healing process. As shown in previous studies, resorption of the matrix begins as early as the fourth week and is nearly complete by the second month.^10,15 This rapid degradation suggests that the matrix is completely replaced by host tissue, rendering the bovine origin of the collagen undetectable. These findings align with data from Vana et al,¹⁶ who demonstrated that the MatriDerm matrix is fully converted into well-organized connective tissue within 12 months.

In both aforementioned studies—focused solely on histological evaluation without DNA analysis—the patient populations consisted exclusively of burn injury cases.^10,16 To date, investigations following secondary surgical procedures after flap loss have not been described in the literature.

The degradation of MatriDerm follows the natural wound healing mechanism, in which the matrix is gradually resorbed by fibroblasts and other host cells. Due to this rapid transformation into neodermal tissue, no traces of the original bovine DNA remain—an observation supported by the histological findings presented in this study.

These properties of MatriDerm support the hypothesis that the material not only provides a temporary scaffold but also facilitates complete integration into human tissue without leaving residual components of the original matrix. The fact that no bovine DNA could be detected further supports our in-house data, which reported no complications in the form of foreign body granulomas or allergic reactions.

CONCLUSIONS

This study highlights the favorable biological, structural, and clinical characteristics of MatriDerm as a dermal substitute. The prompt and complete integration observed suggests that the product enables rapid and effective incorporation into the wound healing process without acting as a physical barrier in later phases of tissue regeneration—unlike Integra, which has been shown to remain detectable years after transplantation,¹⁶ despite manufacturer claims of resorption within 30–60 days.

A key advantage lies in the absence of detectable bovine DNA in MatriDerm. Previous molecular biological analyses failed to identify any residual animal nucleic acids, indicating a high degree of purity and complete decellularization of the collagen–elastin complex. This absence of residual DNA suggests that the bovine starting material is fully resorbed during tissue healing, leaving no xenogeneic cells or tissue components at the recipient site. This is particularly relevant for immunologic safety and long-term biocompatibility, as remaining xenogeneic DNA could potentially trigger immune responses. The molecular confirmation of DNA absence further supports the safety profile of the product and justifies its use in sensitive areas with thin soft tissue coverage.

Regarding sampling from multiple areas, although this would be technically possible, in the present case series, it was limited to a defined site for ethical and practical reasons, avoiding additional tissue trauma. We consider that multiregional sampling would not have substantially altered the results, as histological and molecular findings indicate complete and homogeneous matrix integration across the entire transplantation area. These findings underscore the reliable resorption and tissue incorporation of MatriDerm in clinical applications. Furthermore, the DNA-free nature of the product supports greater ethical acceptability among users and patients with religious or cultural reservations regarding animal-derived tissue products. The 2-stage approach, with initial VAC therapy for wound conditioning followed by MatriDerm application and skin grafting, prolongs the overall reconstruction process compared with a single-stage procedure, which may be disadvantageous for multimorbid or hospitalized patients. There is a risk of matrix dehydration if the dressing is insufficiently moistened or excessive suction is applied after VAC removal, potentially impairing cell migration and integration. The combination of 2 treatment steps also involves higher material costs, additional surgeries, and increased staffing requirements.

Clinically, MatriDerm proved to be an easy-to-handle material with a high matrix take rate. Despite its early resorption, the matrix provided sufficient temporary dermal stabilization and efficiently supported reepithelialization, as demonstrated in our case study. The 1-mm matrix required no secondary silicone layer removal, streamlining surgical workflows compared with products such as Integra. MatriDerm can be used both in joint-related (cross-joint) defects and in chronic wounds without joint involvement. Its application has become established practice in reconstructive and wound surgery, as it provides a stable dermal substitute that supports neovascularization and improves graft take regardless of the anatomical location. Several studies have reported favorable outcomes using Matriderm in chronic, non–joint-related wounds, demonstrating its versatility and reliability in complex soft tissue reconstruction.^6,7

Comparative studies evaluating the integration of other dermal substitute products should be conducted to further validate and contextualize the findings. Future studies should also include an increased number of cases to strengthen the statistical power and generalizability of the results.

DISCLOSURES

Prof. Dragu serves on the advisory board of MedSkin Solutions Dr. Suwelack AG and has received consulting fees from the company. The company had no role in the design, conduct, analysis, or reporting of this study. The other authors have no financial interest to declare in relation to the content of this article.

PATIENT CONSENT

Written informed consent for publication has been obtained from the identifiable patient to publish this article.

The datasets analyzed in this article are not publicly available. Requests to access the datasets should be directed to antek.nicklas@uniklinikum-dresden.de.

ACKNOWLEDGMENT

The authors are grateful to Annett Wenke, Suzanne Manthey, and Kathleen Schütz for excellent technical assistance (histology, qRT-PCR).

ETHICAL APPROVAL

The study was conducted in accordance with the Declaration of Helsinki and approved by the ethics committee (ethical approval number: BO‑EK‑10012022).