Vol. 118 No.

2 August 2014

Resorbable collagen membranes: histopathologic features

Soulafa A. Almazrooa, BDS, DMSc,a Vikki Noonan, DMD, DMSc,b,f and Sook-Bin Woo, DMD, MMScc,d,e
Harvard University, Boston, MA, USA; Boston University, Boston, MA, USA; Brigham and Women’s Hospital, Boston, MA, USA; StrataDx Inc,
Cambridge, MA, USA

Objective. Resorbable collagen membranes (RCMs) are commonly used by oral surgeons, periodontists, and endodontists for
multiple purposes. We report 6 cases of RCMs that did not resorb as expected and describe the histopathologic features.
Study Design. Cases of an unusual fibrillar foreign material were noted in biopsy specimens curetted from bone.
Hematoxylin-eosin and Masson trichrome stains were performed. Clinicians were contacted for detailed clinical information.
Results. There were 3 men and 3 women. RCMs presented as hyalinized, paucicellular, delicate eosinophilic fibrils or a
meshwork without a foreign body reaction. They were refractile and stained for Masson trichrome as expected. These RCMs
persisted longer than expected (2-6 weeks) in 3 cases and may have retarded healing in 5 cases.
Conclusions. Although RCM is supposed to be fairly rapidly resorbable, this material sometimes persists within wound sites without
any obvious foreign body reaction and may retard healing. (Oral Surg Oral Med Oral Pathol Oral Radiol 2014;118:236-240)

Resorbable collagen membranes (RCMs) are manu- RESULTS

factured from allogeneic or xenogeneic sources to
manage oral wounds such as extraction sockets, for
sinus-lift procedures and repairs, and for periodontal or
endodontic surgeries.1-4 They act as scaffolds for bone
deposition in guided bone regeneration (GBR), promote
platelet aggregation, stabilize clots, and attract fibro-
blasts, facilitating wound healing.5-7 They are designed
to resorb within 2 to 32 weeks and are biocompatible,
easy to manipulate, and only weakly immunogenic.7-9
They are available as membranes, plugs, or pads for
ease of use.
The objective of this report is to describe 6 cases of
retained resorbable collagen membranes noted in oral
curettage specimens and to describe the histopathology
of this exogenous material.
MATERIALS AND METHODS
Cases of an unusual fibrillar foreign material were noted
in biopsy specimens accessioned from StrataDx Inc,
Lexington, MA, USA, from January 2013 to December
2013. Patient history and clinical and radiographic
features were obtained by contacting the clinicians by
telephone. Hematoxylin-eosin and Masson trichrome
stains were performed.
a
Graduate student, Department of Oral Medicine, Infection and
Immunity, Harvard School of Dental Medicine.
b
Associate Professor, Boston University Henry Goldman School of
Dental Medicine.
c
Associate Professor, Department of Oral Medicine and Oral Pathol-
ogy, Harvard School of Dental Medicine.
d
Associate Surgeon, Division of Oral Medicine and Dentistry, Brig-
ham and Women’s Hospital.
e
Co-director, Oral Pathology Center, StrataDx Inc.
f by oral surgeons, periodontists, and endodontists for
Associate Pathologist, StrataDx Inc.
Received for publication Feb 25, 2014; returned for revision Apr 16,
2014; accepted for publication Apr 21, 2014.
Ó 2014 Elsevier Inc. Open access under CC BY-NC-ND license.
2212-4403
http://dx.doi.org/10.1016/j.oooo.2014.04.006
Six cases were identified. The demographic data, history,
and clinical information are presented in Table I. The
biopsy specimens were from 3 men and 3 women. Five
cases were curettage specimens from the bone and were
biopsied because of a persistent radiolucency or delayed
healing (Figure 1), and the sixth case represented acci-
dental contamination of a biopsy specimen during an
apicoectomy when the membrane was placed for he-
mostasis (see Table I). In 5 cases, resorbable collagen
was used for ridge augmentation, for GBR, to control
bleeding in an extraction socket, to fill a defect after
removal of a recurrent keratocystic odontogenic tumor
(KCOT), and for hemostasis after an apicoectomy.
Histopathologic findings
All cases (except case 6, which represented contami-
nation) showed granulation and fibrous tissue with a
variable lymphoplasmacytic infiltrate consistent with a
healing wound. In all cases, there were hyalinized
eosinophilic strands of fibrillar material resembling
collagen (Figures 2 and 3). Some of the eosinophilic
strands were present in a meshwork, or as thinner, more
delicate fibrils appearing to be in the process of disin-
tegration (Figure 4, A, B); these fibrils were separated
by fibrous connective tissue containing fibroblasts with
scattered lymphocytes. A foreign body giant cell
Statement of Clinical Relevance
Resorbable collagen membranes are commonly used
multiple purposes. They generally resorb fairly
rapidly but sometimes may persist within wound
sites without any obvious foreign body reaction and
may retard healing.

236
OOOO ORIGINAL ARTICLE
Volume 118, Number 2 Almazrooa, Noonan and Woo 237

Table I. Summary of cases, demographic data, and clinical features

Age/ Time since collagen
Case No. gender History/collagen product use Reason for surgery product use
Case 1 58/F Ridge augmentation using RCM6 Biopsy of right maxillary vestibule for 12 weeks
eSlide: VM00235 recurrent infection after ridge
and VM00234 augmentation
Case 2 84/M Extraction of right mandibular first and second Persistent granulation tissue within socket 6 weeks
eSlide: VM00233 molar; OsseoGuard placed for GBR 6 weeks after extraction
Case 3 71/M Extraction of right mandibular third molar; Persistent radiolucency of socket for 2 8 weeks
eSlide: VM00232 CollaTape placed months
Case 4 47/F Curettage of area between the right Persistent radiolucency 4 weeks
eSlide: VM00231 mandibular first and second premolars
(history of KCOT there); CollaTape placed
Case 5 75/M Sinus tract, apicoectomy; CollaTape placed Persistent sinus tract 4 weeks
eSlide: VM00230
Case 6 68/F Apicoectomy of left maxillary second molar; Persistent periapical radiolucency 0*
eSlide: VM00236 CollaPlug placed
GBR, guided bone regeneration; KCOT, keratocystic odontogenic tumor.
*CollaPlug was placed at the same time as apicoectomy specimen was submitted. Accidental contamination occurred.

Fig. 2. Case 1. Hyalinized, acellular eosinophilic strands of

fibrillar material resembling collagen with fibrosis and mild
chronic inflammation (hematoxylin-eosin, original magnifi-
cation  100). A high-resolution version of this slide is
available as eSlide VM00235.

Fig. 1. Case 2. Persistent ulcerated granulation tissueelike

mass extruding from extraction sockets of teeth 30 and 31
(right mandibular first and second molars).

reaction was not seen. The collagen membrane differed

from the surrounding collagen because of its lack of
cellularity (Figure 5). However, it was refractile in a
fashion similar to collagen (Figure 6). It also stained
positively with the Masson trichrome stain (Figure 7).
There was no evidence of osteoid or woven bone for-
mation in any of the cases.
Fig. 3. Case 5. Hyalinized, acellular eosinophilic strands of
collagen, partially degraded with fibrosis and chronic inflamma-
tion (hematoxylin-eosin, original magnification  100). A high-
resolution version of this slide is available as eSlide VM00230.
ORAL AND MAXILLOFACIAL PATHOLOGY OOOO
238 Almazrooa, Noonan and Woo August 2014

Fig. 4. A, Case 3. Collagen membrane in process of degradation with a mesh-like appearance (top) or as delicate, short fibrils
(bottom) (hematoxylin-eosin, original magnification 200). A high-resolution version of this slide is available as eSlide VM00232.
B, Case 2. Collagen membrane in process of degradation with both thicker, intact bands (top) and more delicate, thin fibrils (center)
(hematoxylin-eosin, original magnification 400). A high-resolution version of this slide is available as eSlide VM00233.

Fig. 5. Case 1. Collagen membrane showing lack of cellu-
larity, insinuated by fibrous tissue, in the process of degra-
dation (hematoxylin-eosin, original magnification 400). A
high-resolution version of this slide is available as eSlide
VM00235.
Fig. 6. Case 1. Collagen membrane strands are refractile in
polarized light, similar to normal collagen (hematoxylin-
eosin, original magnification 200).

DISCUSSION
Collagen is an insoluble fibrous protein that is an
essential component of the connective tissue stroma.
There are at least 16 types of collagen found in inter-
stitial tissues, matrix of bone, cartilage, epithelial and
blood vessel basement membrane, and the vitreous of
the eye, among others.10 Type I, II, and III collagen
constitute 80% to 90% of the body’s collagen;
commercially available collagen products are composed
mainly of type 1 collagen.9 Many of the most
commonly used collagen membranes are derived from
bovine tendon11,12 (Table II). Cross-linkage between
collagen molecules (such as with formaldehyde or
glutaraldehyde)11-13 during the manufacturing process
strengthens the collagen fibrils, increases their stability, Fig. 7. Case 1. Collagen membrane stains in a manner similar
prolongs resorption time, and increases biocompati- to, but more intense than, that of normal collagen (Masson
bility. Resorption of collagen membranes occurs trichrome, original magnification 100). A high-resolution
through biodegradation by inflammatory cells.14 In version of this slide is available as eSlide VM00234.
OOOO
Volume 118, Number 2
Table II. The most commonly used commercially available resorbable collagen membranes
Commercial name (manufacturer)
CollaTape/CollaPlug/CollaCote (Integra LifeSciences Corp, Plainsboro, NJ, USA)
Periogen (Collagen Corporation, Palo Alto, CA, USA)
BioMend (Collagen Matrix Inc, Franklin Lakes, NJ, USA)
BioMend extend (Collagen Matrix Inc)
Ossix (Datum Dental Ltd, Lod, Israel)
Bio-Gide (Geistlich, Wolhusen, Switzerland)
OsseoGuard (Collagen Matrix Inc)
OsseoGuard Flex (Collagen Matrix Inc)
RCM6 (ACE Surgical Supply Co Inc, Brockton, MA, USA)
1985, the Food and Drug Administration approved
CollaCote (Integra LifeSciences Corp, Plainsboro, NJ,
USA), a rapidly resorbable collagen membrane derived
from bovine tendon; subsequently, many of the other
commercially available membranes were approved in
1990.15 Resorbable collagen membranes are commer-
cially available as membranes alone (see Table II) or
impregnated with other materials such as bone
morphogenic protein (Infuse; Medtronic Inc, Minne-
apolis, MN, USA).7,16
Resorbable collagen membranes are frequently used
as wound dressings because they act as a scaffold, pro-
mote platelet aggregation, stabilize clots, and attract fi-
broblasts, facilitating wound healing; they are therefore
often used for GBR.7,9,17,18 Other applications for these
collagen products include ridge augmentation and
grafting of extraction sockets, as well as for sinus lift
procedures, the repair of sinus membrane tears, soft tis-
sue recontouring, and GBR during apicoectomy.7,9,19,20
Historically, collagen membranes exhibit variable
resorption times ranging from 4 to 32 weeks, and the
choice of material depends on the intended use.8,9 If the
intended use is GBR, a more durable collagen mem-
brane with longer resorption time such as OsseoGuard
(Collagen Matrix Inc, Franklin Lakes, NJ, USA) may
be used because of its reported 6- to 9-month resorption
period.8 However, if the intended use is simply to
control bleeding, products with the shortest reported
resorption time of 10 to 14 days, such as CollaTape,
CollaPlug, and CollaCote (Integra LifeSciences Corp),
may be preferable.7
In this report, we describe the clinical and histo-
pathologic findings of resorbable collagen membrane in
6 patients. The membrane material resembled collagen
both in its refractile properties under polarized light and
in the characteristic staining with Masson trichrome
stain. However, the morphology of this material was
different from that of native collagen in that the
resorbable collagen exhibited acellular strands of hya-
linized material often noted to be in the process of
disintegration into short and narrow fibrils, or a mesh-
work, with associated fibrosis and chronic inflammation.
ORIGINAL ARTICLE
Almazrooa, Noonan and Woo 239
Collagen type Collagen source Resorption rate
Type I Bovine tendon 10-14 days
Type I and III Bovine dermis 4-8 weeks
Type I Bovine tendon 6-8 weeks
Type I Bovine tendon 18 weeks
Type I Porcine tendon 4-6 months
Type I and III Porcine skin 24 weeks
Type I Bovine tendon 6-9 months
Type I and III Bovine dermis 6-9 months
Type I Bovine tendon 26-38 weeks
In 3 cases, the resorbable collagen was used to fill
bone defects or control bleeding, and in 2 cases, it was
placed for GBR and ridge augmentation (see Table I).
In case 1, an infection occurred 3 months after ridge
augmentation. Remnants of RCM6 collagen membrane
(ACE Surgical Supply Co Inc, Brockton, MA, USA)
were seen in the biopsy specimen, an expected obser-
vation given that the reported resorption time is 6
months or more.
In case 2, the clinical wound did not heal for 6 weeks
after tooth extractions (see Figure 1), leading the
clinician to perform a biopsy. Remnants of OsseoGuard
membrane (Collagen Matrix Inc) were seen, as ex-
pected given that the reported resorption time is 6
months; but there was no evidence of new bone for-
mation 6 weeks after the procedure. In general, reepi-
thelialization occurs within 4 weeks, osteoid starts to fill
the extraction socket by 2 to 4 weeks, woven bone by 8
weeks, and lamellar bone by 12 weeks.21-24 Similarly,
in cases 3, 4, and 5 there was persistence of CollaTape
(Integra LifeSciences Corp) 8 weeks after extraction, 4
weeks after curettage of a KCOT, and 4 weeks after
apicoectomy, respectively, although this membrane is
reported to typically undergo resorption within 2
weeks. The biopsies did not show significant new bone
formation, and this is particularly striking in case 3,
which was evaluated 8 weeks after extraction.
Although reossification appeared to be delayed in
some cases, it is unclear if the collagen membrane
contributed to this. What is clear is that in 3 of 5 cases
in which the time of insertion was known, the mem-
brane did not resorb in the timeframe expected. Despite
this, the material appeared to be inert and did not elicit a
foreign body reaction.
CONCLUSION
In this report, we describe the histopathologic appear-
ance of resorbable collagen membranes. The majority
of cases were from curettage specimens of persistent
radiolucencies within bone. This material differs from
endogenous collagen in its organization and
morphology but is identical in its refractility and
ORAL AND MAXILLOFACIAL PATHOLOGY
240 Almazrooa, Noonan and Woo
positive staining with the Masson trichrome stain.
Although resorbable collagen membrane is supposed to
be fairly rapidly resorbable, this material sometimes
persists within wound sites without any obvious foreign
body reaction.
We thank all the clinicians who contributed the cases used for
this report. They are Sadru Kabani, DMD, Cambridge, MA,
USA; Annie Amsalem, DDS, Chestnut Hill, MA, USA; Maria
Dona, DMD, Andover, MA, USA; Erich Herbst, DDS,
Baraboo, WI, USA; Patricia Machalinski, DMD, Arlington,
MA, USA; and Arnold Maloff, DMD, Salem, MA, USA.
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Reprint requests:
Soulafa A. Almazrooa, BDS, DMSc
Division of Oral Medicine and Dentistry
Brigham and Women’s Hospital
75 Francis St
Boston
MA 02115
USA
soulafa_almazrooa@hsdm.harvard.edu; salmazrooa@gmail.com