Research

JAMA Facial Plastic Surgery | Original Investigation

Scaffold-Assisted Artificial Hair Implantation in a Rat Model

Joshua K. Au, MD; Miguel Fernando Palma Diaz, MD; Tara Aghaloo, DDS, MD, PhD; Maie A. St John, MD, PhD

IMPORTANCE Current treatments for alopecia with autograft hair transplantation face
limitations that may preclude complete hair restoration and leave patients with donor site
scars. Scaffold assisted artificial hair implantation as demonstrated in a rat model may provide
an adjunct for hair restoration without donor site morbidity.

OBJECTIVE To design and create porous high-density polyethylene (PHDPE) and expanded
polytetrafluoroethylene (ePTFE) hair-bearing scaffolds and evaluate their biocompatibility in
a rat model.

DESIGN, SETTING, AND PARTICIPANTS For this single-institution randomized prospective

animal study, 34 Sprague Dawley rats were randomly selected into 2 groups: 24 rats for direct
implantation and 10 rats for delayed implantation. The direct-implantation group was
randomly divided into 3 subgroups of 8 rats, which were observed for 2, 12, and 24 week.

INTERVENTIONS Each rat dorsum was implanted with 4 scaffolds—PHDPE and ePTFE with
and without hair—in a randomized 4-quadrant manner. The rats in the direct-implantation
group were observed to their selected time points of 2, 12, and 24 weeks. The rats in the
delayed-implantation group were observed for 4 weeks at which, all well-healed scaffolds
without hair were then percutaneously implanted with 2 follicular units of hair. These rats
were then observed for another 4 weeks.

MAIN OUTCOMES AND MEASURES During the clinical observation period, scaffolds were
observed for signs of infection, extrusion, and persistence of follicular units. Following
sacrifice, sagittal sections of scaffold and surrounding skin were fixed in formalin, stained with
hematoxylin-eosin, and evaluated for degree of fibrovascular invasion and acute and chronic
inflammation.

RESULTS Overall 94.5% (86 of 91) of the scaffolds were well healed at time of evaluation (2
week, 100% [32 of 32]; 12 week, 96.3% [26 of 27]; 24 week, 87.5% [28 of 32]); while 85.6%
of artificial hair follicular units were intact at time of evaluation (2 week, 93.8% [30 of 32]; 12
week, 86.7% [26 of 30]; 24 week, 75.0% [21 of 28]). Within the delayed implant group 100%
(19 of 19) of the hair-implanted scaffolds were well healed at 8 weeks, with 94.7% (36 of 38)
of the follicular units intact; 100% of the delayed–hair implant scaffolds were well healed with Author Affiliations: Department of
Head and Neck Surgery, UCLA
86.1% (36 of 38) of the follicular units intact. Kaplan-Meier log-rank analysis showed no Medical Center, Los Angeles,
significant difference in survival between ePTFE and PHDPE scaffolds, as well as scaffolds California (Au, St John); Department
with hair and scaffolds without hair. Upon histological analysis, overall scaffolds with hair of Pathology and Laboratory
Medicine, UCLA Medical Center, Los
were noted to have greater chronic inflammation (95% CI, −0.81 to −1.10; P = .01), and PHDPE
Angeles, California (Palma Diaz);
was noted to have significantly great fibrovascular integration (95% CI, −11.42 to −1.96; UCLA Head and Neck Cancer
P = .01) compared with ePTFE. Program, UCLA David Geffen School
of Medicine, Los Angeles, California
(Palma Diaz, St John); Jonsson
CONCLUSIONS AND RELEVANCE Overall, PHDPE and ePTFE hair bearing scaffolds were well
Comprehensive Cancer Center, UCLA
tolerated in a rat model. Progressive loss of artificial hair may be percutaneously implanted David Geffen School of Medicine,
without significant increases in infection or extrusion. Los Angeles, California (Palma Diaz,
St John); Section of Oral &
Maxillofacial Surgery, UCLA School of
LEVEL OF EVIDENCE NA. Dentistry, Los Angeles, California
(Aghaloo).
Corresponding Author: Joshua Au,
MD, Department of Head and Neck
Surgery, University of California Los
Angeles, 10833 Le Conte Ave, CHS
JAMA Facial Plast Surg. 2018;20(3):230-237. doi:10.1001/jamafacial.2017.2186 62-132, Los Angeles, CA 90095-1624
Published online December 28, 2017. (Joshua.k.au@gmail.com).

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 Scaffold-Assisted Artificial Hair Implantation in a Rat Model
A
lopecia occurs when the normal repopulation of hair
is disrupted. The most common form is androgenic alo-
pecia, with frontotemporal and vertex hair loss, spar-
ing the occipital scalp. Androgenic alopecia affects more than
50% of men by age 50 years.1 The severity of androgenic alo-
pecia has been stratified by the Norwood Classification.2 In ad-
dition to patterned baldness, hair loss may result from alope-
cia areata, an autoimmune inflammatory condition, telogen
effluvium, trauma, or postsurgical scarring.
Treatment of alopecia has included medical, as well as sur-
gical, therapies. Minoxidil and finasteride are approved for medi-
cal treatments of androgenic alopecia.3-6 Currently, autograft
hair transplantation is the gold-standard surgical treatment for
alopecia.7-11 Hair follicles are removed from the nonbalding oc-
cipital scalp in a linear strip by follicular unit transplantation or
through individual punches by follicular unit extraction and
then surgically transplanted to areas of alopecia.7-11 However,
autograft hair transplantation, while able to produce long-
lasting and safe results, is not without morbidity and limita-
tion. Donor site morbidity in follicular unit transplantation re-
sults in a conspicuous occipital linear scar, especially in patients
who wear their hair shorter than 1 to 2 cm.8-11 Follicular unit ex-
traction, adopted to prevent need for a strip of donor hair, is lim-
ited by lower yield in viable follicular units.10,11 Additionally, ow-
ing to the low yield, multiple rounds of hair harvesting may be
required, which may result in donor scalp cobblestoning, hair
thinning, and limit further hair transplant procedures.8,10,11
Patients with advanced hair loss (ie, Norwood VI, VII, or alo-
pecia totalis/universalis) may have such limited donor site hair
that the improvement of hair coverage by autograft hair trans-
plantation may not be possible or may not achieve complete hair
coverage.8 In these patients, a series of artificial hair implants
may be able to create hair coverage where donor site hair is un-
available. In addition, in patients with alopecia from traumatic
scarring, artificial hair implantation may provide coverage in the
scarred tissue without creating further donor site scarring.
Prior attempts at artificial hair implantation were not ap-
proved by the US Food and Drug Administration (FDA) owing
to complications including folliculitis, extrusion, and skin
inflammation.12 A clinical trial13 in India of Biofiber, an Italian
artificial hair, has shown infection rates of 30% and extrusion
rates of 20% per year.
There are numerous examples of safe, FDA-approved im-
plants, including rhinoplasty, malar, and dental implants. Po-
rous high-density polyethylene (PHDPE) and expanded poly-
tetrafluoroethylene (eP TFE) have been shown to be
biocompatible, nonbiodegradable, able to retain shape, and
FDA approved in facial implants.14-23 The goal of this study was
to explore the role of PHDPE and ePTFE scaffold-assisted ar-
tificial hair implantation in a rat model.
Methods
Scaffold Design
The scaffold consisted of a body and lateral flaps in a “t” shape
measuring 10 × 10 × 3 mm (L × W × H) (Figure 1). In head and
neck surgery, t-shaped implants have been used to promote
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Original Investigation Research
Key Points
Question Are porous high-density polyethylene (PHDPE) and
expanded polytetrafluoroethylene (ePTFE) artificial hair-bearing
scaffolds tolerated in a rat model?
Findings In this animal study of 34 rats, 87.5% of the scaffolds
were well healed, and 75% of artificial hair follicular units were
intact at 24 weeks. The analysis showed no significant difference
between ePTFE and PHDPE scaffolds as well as scaffolds with hair
and scaffolds without hair.
Meaning Overall, PHDPE and ePTFE hair-bearing scaffolds are
well tolerated in a rat model, and progressive loss of artificial hair
may be percutaneously replenished without any significant
increase in infection or extrusion.
retention and prevent extrusion of the implant.24 The scaf-
fold was carved in a sterile fashion with a No. 15 blade from
sterile PHDPE (Stryker) or ePTFE blocks (Surgiform).
Scaffold Hair Insertion
When artificial hair was required, 5-cm industrial grade red
kanekalon hair was sterilized in a 5-minute betadine wash. Four
strands of hair were knotted at one end to simulate a follicu-
lar unit. At the other end, the strands of hair were fixed to a
sterile Keith needle. The needle was passed from the base of
the scaffold through the top, pulling the hair through the scaf-
fold until the knotted end was mechanically fixed to the base
of the scaffold body. Each hair bearing scaffold had 2 follicu-
lar units of hair inserted at the one-third and two-third points
of the scaffold body, ensuring at least a 1-mm border of scaf-
fold margin around each follicular unit of hair. Thus, each hair-
bearing scaffold implanted 2 follicular units (Figure 1).
Structural Integrity Evaluation
The tensile strength of the hair fixed to the scaffolds was evalu-
ated to ensure the ability to withstand forces from the activi-
ties of daily living (approximately 0.3 N).25 The hair was
clamped and the scaffold body was suspended from a spring
scale. A sustained load of more than 0.3 N was confirmed for
each scaffold.
Surgical Implantation of Scaffolds in a Rat Model
This experimental protocol was approved by the University of
California, Los Angeles, Institutional Animal Care and Use Com-
mittee. Three-month old male Sprague Dawley rats, weigh-
ing 200 to 250 g, were selected as a wound-healing animal
model.26 Thirty-four rats were randomly selected into 2 groups:
24 rats for direct implantation and 10 rats for delayed implan-
tation. The direct-implantation group was randomly divided
into 3 subgroups of 8 rats that were observed for 2, 12, and 24
week, because, in patients with alloplastic implants, infec-
tious complications usually occurred within 3 months.27
All surgical procedures were performed with aseptic tech-
nique. The rats were placed in the prone position and
anesthetized with inhaled isoflurane 2% to 4% to effect. Bu-
prenorphine 0.05 mg/kg was given subcutaneously for pain
management. Nonsteroidal anti-inflammatory analgesia and
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 Research Original Investigation
Figure 1. Scaffold Design
A Expanded polytetrafluoroethylene B Porous high-density polyethylene
Clinical photographs of t-shaped scaffolds with mechanically fixed hair prior to
implantation.
antibiotics were not used so as not to confound the incidence
of infection. The animal was prepared aseptically by shaving
the dorsum from the caudal aspect of the scapula to the ce-
phalic aspect of the pelvis. The skin was then disinfected with
3 alternating betadine and alcohol scrubs and bland ophthal-
mic ointment was placed in the eyes during anesthesia.
Four-quadrant scaffold implantation was planned with in-
cisions placed 3 cm apart to minimize the potential confound-
ing effect of each implant on the rest. One-centimeter incisions
were made with a No. 15 blade through the panniculus carno-
sus muscle, and blunt dissection deep to the panniculus carno-
sus muscle created a surgical implantation pocket.28-30 Each rat
was implanted with a set of scaffolds including: (1) PHDPE with
hair; (2) PHDPE without hair; (3) ePTFE with hair; and (4) ePTFE
without hair, allowing scaffolds without hair to serve as con-
trols to the scaffolds with hair. The location of each scaffold im-
plantation was randomized by quadrant to control for prefer-
ential animal grooming habits. Each incision was then closed
with 2 simple interrupted 5-0 polypropylene stiches through the
panniculus carnosus muscle and skin. The rats in the direct-
implantation group were observed to their selected time points
of 2, 12, and 24 weeks.
The rats in the delayed-implantation group were ob-
served for 4 weeks, at which point all well-healed scaffolds
without hair were then percutaneously implanted with 2 fol-
licular units of hair. These rats were then observed for an-
other 4 weeks.
During the clinical observation period, scaffolds were ob-
served for signs of infection, extrusion, and persistence of fol-
licular units. Following sacrifice, sagittal sections of scaffold
and surrounding skin were fixed in formalin and stained with
hematoxylin-eosin and evaluated for degree of fibrovascular
invasion, as well as acute and chronic inflammation.
In Vivo Evaluation of Implants
The healing of implants were evaluated postsurgically at 24 hours,
48 hours, 1 week, 2 weeks, 1 month, 3 months, and 6 months,
when applicable. The implant sites were evaluated for signs of in-
fection and extrusion, as well as retention of implanted follicu-
lar units. Implants that were completely extruded and absent
within 48 hours of implantation were noted as extruded samples,
and excluded from follicular unit survival, scaffold survival, and
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Scaffold-Assisted Artificial Hair Implantation in a Rat Model
histological analysis. If implants showed signs of infection and
partial extrusion, the implant was explanted, while the other im-
plants remained in place. Partially extruded implants at final
evaluation were included in follicular unit survival, scaffold sur-
vival, and histological analysis. Completely extruded implants
were lost samples and were excluded from follicular unit, survival,
scaffold survival, and histological analysis.
Data Collection and Analysis
At the designated time points, the 8 rats in each group were eu-
thanized. The presence of infection or extrusion was noted and
the number of retained follicular hair units was recorded. The
implants were then excised from the rat dorsum with a 5-mm
margin of tissue. Specimens were fixed in 10% formalin for 48
hours, paraffin sectioned to 7 micron thickness at the level of the
artificial hair shaft, and stained with hematoxylin-eosin for his-
tological analysis.31 Analysis included the degree of acute and
chronic inflammation, percentage of fibrovascular integration,
and the degree of inflammation at the hair insertion site of the
scaffold. Periscaffold acute and chronic inflammation, as well
as hair shaft inflammation, were measure in a semiquantitative
scale: 0, no inflammation; 1, mild inflammation, small number
of disseminated neutrophils or lymphocytes; 2, moderate in-
flammation, moderate number of neutrophils or lymphocytes
clustered in groups; or 3, severe inflammation, large number of
cells with dense cellular infiltrate.31 Fibrovascular integration was
measured as a percentage of the scaffold integrated by surround-
ing fibrovascular tissue.32
Statistical Analysis
Power calculations with G*Power (Heinrich-Heine-Universität
Düsseldorf) confirmed the need for a minimum of 7 rats per
group to establish if PHDPE scaffold exhibits less infection and
better biocompatibility than the ePTFE scaffold and may serve
as a hair–containing artificial hair implant in a rat model.33 This
was based upon the hypothesis that PHDPE, with its larger pore
size and potential for fibrovascular integration will have a large
(effect size of f = 0.8) impact on decreasing infection and extru-
sion; α was set to .05, and the power at 0.8.
Statistical analyses were performed using SPSS 24 soft-
ware (IBM Corp). Analysis of acute inflammation, chronic in-
flammation, fibrovascular integration, and hair shaft inflam-
mation were evaluated between scaffolds with and without
hair, between different scaffold materials, and across sacri-
fice time points by independent-sample t test analysis. Statis-
tical significance was determined at the P < .05 threshold.
Scaffold survival and follicular unit survival was evalu-
ated by the Kaplan-Meier method with the pooled data of the
2 week, 12 week, and 24 week groups. Differences in survival
were formally evaluated using the log-rank test. Similarly, scaf-
fold and follicular unit survival analysis of the delayed group
were evaluated by Kaplan-Meier log-rank test.
Results
Overall, 94% (86 of 91) of the implanted scaffolds were well
healed at the time of evaluation (2 week, 100% [32 of 32]; 12
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 Scaffold-Assisted Artificial Hair Implantation in a Rat Model Original Investigation Research

week, 96% [26 of 27]; 24 week, 88% [28 of 32]). Of the 2-week
Figure 2. Animal Model
group, all scaffolds were well healed. Of the 12-week group, 5
scaffolds (1 PHDPE with hair, 2 PHDPE without hair, 2 ePTFE
without hair) were dislodged by animal grooming within a day
after implantation and were excluded from the study. Of the
remaining 27 scaffolds, 26 were well healed at 12 weeks, and
only 1 scaffold (ePTFE with hair) was partially extruded upon
final evaluation. Of the 24-week group, 28 of 32 scaffolds were
well healed at the time of evaluation (Figure 2). Three scaf-
folds had extruded (2 PHDPE with hair, and 1 PHDPE without
hair) and 1 PHDPE with hair had partially extruded upon final
evaluation. When analyzing scaffold survival based on mate-
rial, there was no difference in scaffold survival between ePTFE
and PHDPE scaffolds (Kaplan-Meier log-rank, P = .30). Simi-
larly, there was no scaffold survival difference between scaf-
folds with hair and scaffolds without hair (Kaplan-Meier log-
rank, P = .72).
Of the delayed group, 1 scaffold (PHDPE with hair) was dis-
lodged by animal grooming within 48 hours of implantation
and excluded from the study. In addition, 2 scaffolds (1 ePTFE
and 1 PHDPE) had superficial abrasion noted at 4 weeks and
did not have hair implanted and were excluded from the
Well-healed 24-week postimplantation rat dorsum with PHDPE and ePTFE
remainder of the study. All 19 of the initially implanted scaf- scaffolds with hair on the left and control PHDPE and ePTFE scaffolds without
folds were well healed, and all 18 of the delayed implanted hair on the right. PHDPE indicates porous high-density polyethylene; ePTFE,
scaffolds were well healed at the 8 week time of evaluation. expanded polytetrafluoroethylene.

Kaplan-Meier log-rank analysis showed no significant differ-

ence in scaffold survival between initially implanted scaf-
folds and scaffolds implanted with hair 4 weeks after implan-
tation (P = .34). There was also no significant difference in
scaffold survival (P = .32) when analyzing between scaffold ma-
terials (ePTFE vs PHDPE) in the delayed-implantation group
by Kaplan-Meir log-rank analysis.
Overall, 86% of artificial hair follicular units were intact
at time of evaluation (2 week, 94% [30 of 32]; 12 week, 87%
[26 of 30]; 24 week, 75% [21 of 28]). There was no statistically
significant difference of follicular unit survival between ePTFE
and PHDPE scaffolds (Kaplan-Meier log-rank, P = .72) based on
scaffold material. Within the delayed-implantation group, 95%
(36 of 38) of the initially implanted follicular units remained
intact; 89% (32 of 36) of the delay-implanted follicular units
remained intact. Kaplan-Meier log-rank analysis showed no sig-
nificant difference in follicular unit survival (P = .24) be-
tween initially implanted scaffolds and delayed-implanta-
tion scaffolds. There was also no significant difference in
follicular unit survival (P = .68) between ePTFE and PHDPE
scaffolds in the delayed-implantation group.
All animals survived the procedures. No major complica-
tions were noted postoperatively. All areas with previously ex-
truded implants were well healed and did not require sacri-
fice of rats or explantation of neighboring scaffolds.
Upon histological analysis, there was no statistical differ-
ence between materials or hair status in the scaffolds at the
2-week time point (Table 1). At the 12-week time point, there
were statistical differences in chronic inflammation and de-
gree of fibrovascular integration between ePTFE and PHDPE
scaffolds. At the 24-week time point, there was statistically sig-
nificant greater acute and chronic inflammation of scaffolds
with hair than scaffolds without hair (Table 1). There was no
significant difference between the level of inflammation of the
hair shafts of ePTFE and PHDPE scaffolds with hair at all time
points (Table 1; Figure 3). Overall, scaffolds with hair were noted
to have greater chronic inflammation (95% CI, −0.81 to −0.10;
P = .01), and PHDPE was noted to have significantly greater fi-
brovascular integration (95% CI, −11.42 to −1.96; P = .01) com-
pared with ePTFE (Table 1).
Histological analysis of the delayed group noted signifi-
cant differences in fibrovascular integration, chronic inflam-
mation, and hair shaft inflammation between ePTFE and
PHDPE (Table 2). However, notably, there were no significant
differences in acute inflammation, chronic inflammation, fi-
brovascular integration, or hair shaft inflammation between
scaffolds with hair and scaffolds with delay-implanted hair.
Discusssion
In this study, artificial hair-bearing scaffolds were engi-
neered from ePTFE and PHDPE. At 24 weeks, 75% of artificial
hair follicular units were intact with no significant difference
between follicular unit survival between ePTFE and PHDPE
scaffolds. This rate of retention is less than the rates of hu-
man hair turnover of 0.1% per day5 and previous human stud-
ies of individual artificial hair implants of 15% to 20% per year.10
However, lower rate of follicular unit retention may be ex-
plained by the social grooming of rats, which may place re-
petitive tensile and sheering forces on the follicular units. Fu-
ture implants may be engineered to withstand these greater
strains from social grooming.
At 24 weeks, 88% of the implanted scaffolds were intact
and well healed at the time of evaluation. This is comparable

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 234
Table 1. Direct-Implantation Group Histological Evaluation by Student t Test

Hair Evaluation Hair Shaft Evaluationa Material Evaluation

ePTFE PHDPE
Without Hair Without Hair Total Without ePTFE With ePTFE With ePTFE Without
(Mean), (Mean), Hair (Mean), Hair (Mean), Hair (Mean), Hair (Mean),
ePTFE With PHDPE With With Hair PHDPE With PHDPE With PHDPE Without Total ePTFE (Mean),
Time Postprocedure Hair (Mean) P Value hair (Mean) P Value (Mean) P Value Hair (Mean) P Value Hair (Mean) P Value Hair (Mean) P Value PHDPE (Mean) P Value
2 Weeks
Acute inflammationa 0.00, 0 0.375 .18 0.750, 0.750 >.99 0.375, 0.563 .57 1.571, 1.286 .55 0.375, 0.750 .46 0.000, 0.750 .09 0.188, 0.750 .08
Research Original Investigation

Chronic 1.375, 1.625 .45 1.500, 1.750 .51 1.438, 1.688 .30 1.625, 1.750 .74 1.375, 1.500 .71 .605 (1.500-1.625) .61
inflammationa
Fibrovascular 10.625, .61 9.375, .61 10.646, .46 13.125, 13.125 >.99 7.289, 13.742 .82 .884 (11.875-11.250) .88
integration, % 13.125 13.125 13.022
12 Weeks

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Acute inflammationa NA NA NA NA NA NA 1.000, 1.250 .58 NA NA NA NA NA NA
Chronic 0.571, 0.000 .11 0.875, 1.000 .41 0.500, 0.733 .30 0.571, 0.875 .34 0.000, 1.000 <.001b 0.3077, 0.929 .002b
inflammationa
Fibrovascular 2.143, 0.833 .60 15.625, .37 6.667, 9.333 .42 2.1429, 15.625 .002 0.833, 12.500 <.001b 1.539, 14.286 <.001b
integration, % 12.500
24 Weeks
Acute inflammationa 0.000, 1.333 .04b 0.000, 0.125 .33 0.000, 0.643 .04b 1.333, 1.429 .81 1.333, 0.125 .047b NA NA 0.615, 0.063 .08
b b
Chronic 0.143, 1.667 .02 0.250, 0.750 .12 0.200, 1.143 .01 1.667, 0.750 .13 0.143, 0.250 .64 0.846, 0.500 .33
inflammationa
Fibrovascular 13.333, .10 15.625, .73 14.643, .54 2.500, 18.125 .01b 13.333, 15.625 .79 7.917, 16.875 .08

JAMA Facial Plastic Surgery May/June 2018 Volume 20, Number 3 (Reprinted)
integration 2.500 18.125 11.429
Compiled
Acute inflammationa 0.000, 0.524 .03b 0.273, 0.292 .93 0.140, 0.400 .11 1.300, 1.318 .94 0.524, 0.292 .39 0.000, 0.272 .11 0.262, 0.283 .90
Chronic 0.571, 1.286 .02b 0.909, 1.125 .33 0.744, 1.200 .01b 1.286, 1.125 .55 0.571, 0.909 .15 0.929, 1.022 .61
inflammationa
Fibrovascular 8.500, 6.429 .50 12.500, .39 10.600, .77 6.429, 15.625 .01b 8.500, 12.500 .27 7.439, 14.120 .01b
integration, % 15.625 11.333
Abbreviations: PHDPE, porous high-density polyethylene; ePTFE, expanded polytetrafluoroethylene. neutrophils or lymphocytes clustered in groups; or 3, severe inflammation, large number of cells with dense
a cellular infiltrate.
Scores are based on a semiquantitative scale of inflammation: 0, no inflammation; 1, mild inflammation, small
b
number of disseminated neutrophils or lymphocytes; 2, moderate inflammation, moderate number of Comparison is statistically significant.

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Scaffold-Assisted Artificial Hair Implantation in a Rat Model

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 Scaffold-Assisted Artificial Hair Implantation in a Rat Model Original Investigation Research

Figure 3. Scaffold Histological Evaluation

A Original magnification ×2 B Original magnification ×2

Representative 24-week
hematoxylin-eosin of (A) PHDPE
(top) and ePTFE (bottom) without
C Original magnification ×20 D Original magnification ×20 hair and (B) ePTFE (top) and PHDPE
(bottom) with hair scaffolds.The blue
arrowheads indicate minimal
fibrovascular integration, and the
yellow arrowheads indicate moderate
fibrovascular integration. High-power
hematoxylin-eosin of (C) ePTFE
scaffold with hair noting mild chronic
inflammation (magenta arrowhead)
of the hair shaft, and (D) PHDPE
scaffold with hair noting moderate
chronic inflammation and focal giant
cell reaction (black arrowheads).

Table 2. Delayed-Implantation Group Histological Evaluation by Student t Test

Hair Evaluation Material Evaluation

ePTFE
ePTFE dH PHDPE dH With Hair Total
(Mean), (Mean), (Mean), ePTFE dH ePTFE
ePTFE PHDPE PHDPE (Mean), (Mean),
Histological With Hair With Hair Total dH With Hair PHDPE dH PHDPE
Analysis (Mean) P Value (Mean) P Value With Hair P Value (Mean) P Value (Mean) P Value (Mean) P Value
Acute 0.000, .36 NA NA 0.000, .34 0.200, .36 NA NA 0.105, .34
inflammationa 0.200 0.105 0.000 0.000
Chronic 0.444, .70 1.111, >.99 0.778, .79 0.600, .19 0.444, .01b 0.526, .01b
inflammationa 0.600 1.111 0.842 1.111 1.111 1.111
Fibrovascular 6.111, .17 21.667, >.99 13.889, .47 1.500, <.001b 6.111, .002b 3.684, <.001b
integration, % 1.500 21.667 11.053 21.667 21.667 21.667
Hair shafta 1.111, .66 1.556, .35 1.333, .86 1.000, .002b 1.111, .12b 1.053, .001b
1.000 1.778 1.368 1.778 1.556 1.667
Abbreviations: dH, delayed hair implantation; ePTFE, expanded or lymphocytes; 2, moderate inflammation, moderate number of neutrophils
polytetrafluoroethylene; PHDPE, porous high-density polyethylene. or lymphocytes clustered in groups; or 3, severe inflammation, large number
a
Scores are based on a semiquantitative scale of inflammation: 0, no of cells with dense cellular infiltrate.
b
inflammation; 1, mild inflammation, small number of disseminated neutrophils Comparison is statistically significant.

to prior studies in rat models with PHDPE and ePTFE.34,35 Well-
healed scaffolds may provide a milieu for further implanta-
tion of artificial hair. Delayed implantation of hairs after 4 weeks
had no significant impact on follicular unit survival or scaf-
fold survival. In this manner, hair implantation may mimic hair
turnover by replenishing hairs lost to activities of daily living.
That we know of, this study is the first to demonstrate the
implementation of scaffold assisted hair implants. The benefit
of delayed hair implantation to replenish hair attrition showed
no increased rate of inflammation or scaffold extrusion.
Overall, 6 implants were extruded fewer than 48 hours af-
ter implantation, likely from social animal grooming (ie, bit-
ing of sutures) and excluded from the study. However, we can-
not exclude early technical failure as the 5 scaffolds extruded
from the 12-week group were among the first implanted over-
all in the study. One additional scaffold extruded following im-
plantation within the delayed-implantation group. Animals
were housed in pairs owing to the social nature of rats. The high
overall retention of implants accentuates the robust healing
despite the persistent contamination and manipulation from
social grooming. The extent of postsurgical manipulation by
human patients may be better controlled than the social groom-
ing of rats and may improve outcomes. Finally, the location
of implantation in the rat dorsum, which is extremely mo-
bile, also places the implants at increased risk of explanta-
tion. As the scalp exhibits limited mobility, hair-bearing scaf-
fold implantation would be expected to have improved
retention relative to the mobile rat dorsum.
Overall, ePTFE scaffolds extruded more often (n = 7; 6 fully
extruded, 1 partially extruded) compared with PE scaffolds (n = 2;

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 Research Original Investigation Scaffold-Assisted Artificial Hair Implantation in a Rat Model

1 fully extruded, 1 partially extruded). However, Kaplan-Meier
log-rank analysis did not show a significant difference in over-
all scaffold survival. Multiple studies have suggested that the po-
rous character of PHDPE promotes a greater degree of fibrovas-
cular integration and decreased infection and extrusion, which
was suggested by this study.34,35 This increased fibrovascular in-
tegration was noted to be associated with increased acute and
chronic inflammation in contrast to prior studies.35
Scaffolds that were completely extruded and absent were
excluded from histological analysis, as well as follicular unit
and scaffold survival analysis. As a result, the histological re-
sults presented are likely biased toward less inflammation and
infection because extruded scaffolds were likely associated
with greater inflammation and infection. Additionally, the fol-
licular unit survival analysis may overestimate follicular unit
survival, which would likely be less in infected scaffolds.
Limitations
It has been well studied and documented that alloplastic mate-
rials may serve as long-term soft tissue implants.14-23 The limi-
tation of this concept in the setting of an artificial hair transplant
is that the hairs extruding from the implanted scaffold remain
through the skin and remain a potential nidus for infection.35 In
this study, scaffolds with hair did not show any clinical purulence
or infection. Notably, scaffolds with hair were noted to have
greater degrees of acute and chronic inflammation at 24 weeks;
however, scaffolds with hair did not have any significant differ-
ence in survival compared with scaffolds without hair. Future
studies may evaluate the association between these levels of in-
flammation with scaffold and hair survival at longer time points.
With the results of this study, we demonstrate the feasi-
bility of scaffold assisted artificial hair implantation. In the fu-
ture, alterations may be made to the scaffold design, includ-
ing alternative mechanical and chemical binding of the artificial
hair to the scaffold to increase follicular unit retention. Other
biocompatible materials may also be considered to minimize
inflammation and infection. Additionally, the scalable implan-
tation of artificial hairs within biocompatible scaffolds must
be evaluated. Future scaffold designs may be hybridized to in-
clude a porous exterior but a nonporous interior that may pro-
vide additional immunologic protection of the artificial hair
and greater tensile strength to anchor hairs. Production of the
scaffolds themselves may be mechanized by 3-dimensional
printing or produced through molds. Scaffold extrusion may
be minimized with multilayer soft tissue closure. In addition,
the scaffold itself may be anchored to underlying soft tissue,
periosteum, or bone. Finally, the art of hair implantation must
take into account the natural angle of hair as it exits the fol-
licles. Future implants may be designed with directionality to
mimic the aesthetic of natural hair.
Conclusions
That we know of, this study is the first to demonstrate the
implementation of scaffold assisted artificial hair implanta-
tion, and PHDPE and ePTFE artificial hair-bearing scaffolds
were well tolerated in a rat model. In addition, delayed hair im-
plantation to replenish hair attrition showed no increased rate
of inflammation or scaffold extrusion.

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Accepted for Publication: October 8, 2017. 1. Otberg N, Finner AM, Shapiro J. Androgenetic Surg. 2008;24(4):404-413.

Published Online: December 28, 2017.
doi:10.1001/jamafacial.2017.2186
Author Contributions: Dr Au had full access to all
of the data in the study and takes responsibility for
the integrity of the data and the accuracy of the
data analysis.
Study concept and design: Au, Aghaloo, St John.
Acquisition, analysis, or interpretation of data: Au,
Palma Diaz.
Drafting of the manuscript: Au.
Critical revision of the manuscript for important
intellectual content: All authors.
Statistical analysis: Au.
Obtained funding: Au, Aghaloo.
Study supervision: Aghaloo, St John.
Conflict of Interest Disclosures: None reported.
Funding/Support: This study was supported by a
Leslie Bernstein Resident Research Grant (grant No.
AAO-HNSF CORE-AAFPRS).
Role of the Funder/Sponsor: The funder/sponsor
had no role in the design and conduct of the study;
collection, management, analysis, and
interpretation of the data; preparation, review, or
approval of the manuscript; and decision to submit
the manuscript for publication.
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