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*Indicates statistical signi ficance as determined by 2-tailed paired t-test
All comparisons were made between baseline scores and individual post-injection
timepoint.
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on the side of injection in two patients 1 day after the ini-
tial injection
No safety events were reported from any ofthe injections ( n=43) throughout the duration of the
trial.
All patients continued to experience subjectively
improved voice outcomes, with the improved overall qual-ity, loudness, vocal endurance, and less strain andbreathiness at 1 month
Two patients noted that theimprovements were sustained until 3 weeks following thefirst injection when they experienced a slight deteriora-
tion but did not return to their baseline dysphonia
Eightpatients continued to experience improved voice qualityand resonance 1 month following the second injection.Two patients reported sustained voice quality at the levelexperienced after the initial injection with no notableimprovement thereafter
All patients reported subjectiveimprovement in their voice 1 month after the third injec-tion, of which three experienced their best overall voiceenhancement
Two patients consistently experienced
gradual deterioration in their voice quality and noted
voice instability as they neared the one-month timepointfollowing each injection.
DISCUSSION
While the application of regenerative medicine tech-
niques in laryngology holds great promise there is a pau-city of human data on the use of PRP
This prospectivecohort study demonstrated a favorable safety pro file for
the use of serial in-of fice vocal fold injections of autolo-
gous PRP among patients with vocal disturbances due tovocal fold atrophy and scar
There were no adverse eventsor peri-procedural complications across 43 PRP injectionsin 12 patients
The practicality of in-of fice procedures has
been embraced in laryngology as they circumvent the useof general anesthesia and the need for an operating roomand staff.
24,25The bioactive components in PRP such as
growth factors, cytokines, and cell adhesion molecules areself-renewing
Moreover, the plasma derivative tissueproduct is reliably reproduced via routine blood drawsand minimal subsequent manipulation
In this trial,blood collection and centrifugation added approximately10–15 min of preparation time
Blood collection, PRP
product preparation, and treatment can be completed in atimely manner rendering the process feasible for theambulatory care setting.
Lamina propria defects found in vocal fold atrophy
and scar represent challenging pathologies to treat.
3Ther-
apeutic interventions include surgical and non-surgicaloptions including tissue transplantation, angiolytic lasertreatments, and voice therapy
Surgeons must consider thediverse roles of the larynx during respiration, phonation,and deglutination
26,27to preserve functional capacity fol-
lowing treatment.2,28Pathologic healing from scar tissue
can lead to persistent dysphonia that impairs appropriatevocal fold approximation and natural dynamic oscillationrequired for clear resonant voice sounds.
3Moreover, there
is no substance to replace the intricate framework of theSLP
Prior to trial enrollment, all patients underwentsome form of previous treatment including steroid injec-tions, injection augmentation, or surgical scar revision.Despite these interventions, these patients continued to
have residual vocal de ficits despite temporary improve-
ment seen in some instances
All participants expresseddissatisfaction with their vocal capabilities during thebaseline evaluation.
PRP is a biological material shown to stimulate host
tissue rejuvenation without eliciting immune rejection asit is derived from the patient ’s own blood
The composi-
tion of PRP consists primarily of a high concentration ofplatelets and growth factors but can also include whiteblood cells and other vasoactive and chemotactic agents.
29
PRP releases growth factors that expedite wound healingvia cell proliferation, matrix formation, osteoid produc-tion, connective tissue healing, angiogenesis, and collagensynthesis.
30,31PRP injections have been shown to have a
broad range of applications in tissue sealing, stabiliza-tion, scar maturation, osteogenesis, and a
lopecia acrossvarious surgical specialties from orthopedics to cosmeticsurgery with virtually no adverse side effects.
32–34In vivo
studies revealed the effect of PRP in vocal fold healing in
rabbit models following acute vocal fold injury.29In oto-
laryngology, the wound healing properties of PRP havepreviously been used to treat tympanic membrane perfo-ration.
35This prospective clinical report on the use of
PRP in the human larynx is unique and builds on recentinterest in commissioning bioactive componen
ts, includ-ing fibroblast growth factors and autologous bone
marrow-derived mesenchymal stromal cells, to treatpathologies of the head and neck
Recently Woo et al.reported short-term voice improvements following inof fice
PRP injections with 11 patients receiving three injec-tions.
26While our preliminary work set out to show the
safety and tolerability of PRP injections in an ambulatorycare setting, many of the patients expressed subjectiveimprovements occurring after a four-injection series
Thestandardized design of our prospective trial, formattedwith consistent follow-up after four unilateral vocal foldinjections, provides a unique and controlled studymethod
As a newly emerging therapeutic avenue in lar-yngology, our findings contribute to the scarcity of litera-
ture exploring the potential use of PRP injections as asuitable treatment modality for patients with vocal foldscar and atrophy
Our results are consistent with thesafety of PRP injections described by Woo et al., and fur-ther support the use of PRP precisely because of theirsimilarity.
All patients underwent treatment without dif ficulty
or complications
There were no accounts of laryngealedema, local in flammatory reaction, dysphagia, or dys-
pnea
Mild discomfort was noted on the side of injectionin two patients 1 day after the initial injection
Patientsin our trial expressed a variable range of voice improve-
ment
Three patients described a mild roughness in the
quality of their voice for 3 –5 days following the first injec-
tion which subsequently resolved
One patient went on toexperience a similar occurrence at their second injection.Patient experiences re flected a general trend of improve-
ment with consecutive PRP injections
Three accountsacross two patients described sustained improvement for3 weeks following treatment before perceiving remissionin voice quality
Generally, patients experienced vocal
Laryngoscope 133: March 2023 van der Woerd et al.: Serial PRP Injections for Vocal Fold Atrophy and Scar
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quality and consistency that eventually spanned the
month between injections
Interestingly, three subjectsexperienced their best overall voice improvement afterinjection number three
All patients who received fourPRP injections were satis fied with the improvement of
their voice and expressed interest in continued treatmentbeyond the completion of their trial participation.
VHI-10 and VFI scores mirror the trend of gradual
improvement
At 1 week after the first PRP injection, the