Keywords
adipose tissue - bioprinting - diabetic foot - limb salvage
Introduction
Preserving lower extremity function is a primary objective for physicians treating
patients with diabetic foot ulcers (DFUs).[1] Reconstructive surgeons consider various reconstructive options to salvage limbs.
Flap reconstruction often yields optimal outcomes; however, its application can be
challenging in patients with severe peripheral artery disease (PAD) or those unable
to tolerate lengthy operations due to multiple comorbidities.[2] Consequently, these patients frequently undergo minor or major amputations, resulting
in a significant decline in their quality of life. Furthermore, long-term mortality
rates are substantially high among individuals who have undergone lower extremity
amputations, particularly when accompanied by risk factors such as renal disease,
diabetes, and PAD.[3]
[4] Therefore, there is a necessity to develop novel strategies for limb salvage in
patients with DFUs.
Autologous fat grafting can be a promising candidate for new treatment options. It
is a frequently performed procedure in plastic surgery, serving multiple purposes
such as body contour correction and rejuvenation.[5] It is popular due to its advantages, including less invasiveness, easy accessibility,
and less donor site morbidity.[6] Recently, there has been an increase in studies demonstrating the potential of autologous
fat grafting in promoting wound healing.[7] This increasing interest has led to the development of innovative approaches. Three-dimensional
bioprinted autologous minimally manipulated homologous adipose tissue (3D-AMHAT) is
a newly developed treatment combining autologous fat grafting and 3D printing technique.[8]
[9]
[10]
[11] In this article, we present our experience in utilizing 3D-AMHAT for limb salvage
in patients who were considered challenging candidates for conventional reconstructive
surgery.
Idea
A 78-year-old female patient presented to our hospital with complaints of right foot
pain. She had a medical history of type 2 diabetes mellitus, end-stage renal disease,
and PAD. Upon examination, an eschar measuring approximately 1 cm in diameter was
observed in the region of the fifth metatarsal bone on her right foot. Lower extremity
vascular evaluation revealed an ankle brachial index of approximately 0.5, indicating
severe stenosis below the right ankle. The patient underwent percutaneous transluminal
angioplasty and received regular follow-up; however, her condition progressively worsened,
resulting in deepening ulcer and the detection of concomitant osteomyelitis on radiologic
examination. To prevent the further progression of osteomyelitis, treatment of the
already necrotic areas was necessary. As a result, she underwent a minor amputation
involving parts of the fourth and fifth metatarsal bones. Despite the amputation,
the patient's diabetic foot did not exhibit significant improvement, and she developed
additional lesion on the heel ([Fig. 1]). The patient and her family expressed a strong desire to preserve her limb function
to the greatest extent possible. During the multidisciplinary meeting, considering
her poor vascular condition, age, comorbidities, and the presence of an ongoing DFU
on the heel, we recommended amputating her foot. However, the patient and her family
declined the amputation and requested an alternative treatment option. Subsequently,
we decided to reconstruct her foot using 3D-AMHAT, conservatively resecting the necrotic
tissue and administering antibiotics to suppress osteomyelitis.
Fig. 1 Preoperative photograph of patient's right foot showing large defect on the lateral
aspect (A) and necrosis on the heel (B).
Under general anesthesia, standard liposuction techniques were employed to harvest
fat from the patient's abdomen. The lipoaspirate was then centrifuged for 5 minutes
at 3,000 rpm, and the second layer was collected into a syringe. The patient's wound
was captured and converted into three-dimensional image files using NewCreatorK software
(ROKIT Healthcare, Seoul, Korea). According to these files, the 3D bioprinter first
printed a scaffold, which was later separated from the patch. Subsequently, a syringe
containing lipoaspirates and another filled with fibrin glue (Tisseel; Baxter AG,
Vienna, Austria) were inserted into the 3D bioprinter. The lipoaspirates and fibrin
glue were then printed in the scaffold in sequence. After hardening, the printed AMHAT
was applied to the defect, and a nonadherent dressing, such as Mepitel (Mölnlycke
Health Care AB, Gothenburg, Sweden), was placed over it. Subsequently, a secondary
dressing comprising foam dressing and cast padding was applied ([Figs. 2]
[3]
[4]).
Fig. 2 A diagram showing the flow of procedure of 3D-AMHAT. 3D-AMHAT, three-dimensional
bioprinted autologous minimally manipulated homologous adipose tissue.
Fig. 3 Intraoperative photograph showing autologous fat being harvested by liposuction and
printed by a 3D printing machine.
Fig. 4 Intraoperative photograph showing printed 3D-AMHAT patch being grafted to patient's
defect. 3D-AMHAT, three-dimensional bioprinted autologous minimally manipulated homologous
adipose tissue.
The patient's wounds were assessed on a weekly basis, and she was discharged approximately
2 weeks after the surgery. The AMHAT graft was well attached and successfully integrated
without any complications such as autolysis, graft failure, or infection. The previously
large defect with exposed bone showed healthy granulation tissue coverage. At the
6-week postoperative follow-up visit, a reduction in the wound size by half was confirmed.
The wound on the lateral aspect of the foot have completely epithelialized, and the
wound on the heel has decreased in size by approximately 75% ([Fig. 5]).
Fig. 5 Postoperative photograph after 6 weeks (A) and 12 weeks (B). The size of the wound reduced to less than half after 6 weeks after surgery, and
complete epithelization was observed on the lateral aspect of the foot 12 weeks after
surgery without additional treatment.
Discussion
Debridement plays a crucial role in the treatment of DFUs, particularly when necrotic
tissue is present. Following debridement, additional reconstructive measures such
as flaps or skin grafts are often necessary for wound closure.[12] However, reconstruction may not always be feasible, particularly in patients with
multiple comorbidities and extensive defects. In cases where reconstruction is not
possible, amputation may be considered to prevent further deterioration of the condition.
But it is important to note that amputation, especially in high-risk patients, can
have a significant impact on the patient's overall health and decrease their life
expectancy.[13] Therefore, there is a need for alternative reconstructive options that can help
avoid major amputations, which significantly impact the patient's quality of life
and overall morbidity. Therefore, we propose fat grafting as a promising and innovative
option for addressing these challenges.
Fat grafting has been widely used in various fields of plastic surgery, but it has
traditionally been considered difficult to reconstruct wounds with raw surfaces using
fat grafts alone. Additionally, fat grafting has not been commonly utilized for the
treatment of chronic wounds. The mechanism by which fat grafts integrate into the
wound site has not been fully elucidated. However, emerging studies suggest that fat
grafts promote wound healing and exert a vasogenic effect.[13]
[14]
[15]
[16] Lipoaspirate, which is obtained during fat grafting, contains cells such as preadipocytes
and multipotent adipose-derived stem cells. These cells contribute to a vasogenic
effect in hypoxic conditions, thereby facilitating wound healing.[4]
[5] Previously, fat grafts lacked a regular shape, making it challenging to cover irregularly
shaped soft tissue defects. However, advancements in 3D printing technology and scaffold
materials have made it possible to create fat grafts with precise and regular shapes.
Moreover, the use of 3D scanning allows accurate replication of irregular wound shapes,
enabling the application of fat grafts to such wounds. The relative simplicity and
shorter operative time of fat grafting make it a suitable option for patients at high
risk for surgery, and the procedure can be performed under local anesthesia.
There have been few prior studies on the use of 3D-AMHAT for treating DFUs, and none
have specifically addressed the treatment of multiple DFUs in distinct vascular territories.[8]
[9]
[10]
[11] Our case demonstrates successful reconstruction using 3D-AMHAT in a high-risk patient
with multiple DFUs. However, there are some limitations to our study. Firstly, the
complete epithelialization time of approximately 12 weeks in our case differs slightly
from previous studies, which reported complete epithelialization within 6 to 8 weeks.
However, this discrepancy is likely attributed to statistical bias due to considerations
of the patient's age, underlying diseases, and the fact that the treatment was performed
in a single case. Additionally, we could not exclude the possibility that the patient's
fat cells had a relatively diminished healing potential due to the patient's old age.
Secondly, there is limited understanding of the action of fibrin glue, which may potentially
aid in wound healing. Further research is needed to clarify the influence of fibrin
glue in this regard.
In our case, the patient's preference for a quick return to daily life and reluctance
towards additional surgery resulted in discharge with a plan for secondary wound healing.
However, it is anticipated that the epithelialization time could be further reduced
by combining 3D-AMHAT with skin grafting in patients seeking expedited treatment.
The significance of this case lies in the successful salvage of the limb using a fat
graft in a patient with multiple DFUs. This suggests that reconstruction surgeons
should consider fat grafting as a valuable option for DFU treatment.
