Progress in Vocal Fold Regenerative Biomaterials: An Immunological Perspective

Abstract

The vocal folds are functional organs located in the larynx that play a critical role in our daily breathing, speech, and swallowing functions. A key structural feature of the vocal folds is their delicate mucosa, which consists of a thin, layered epithelium and underlying extracellular matrix (ECM)-rich lamina propria. [1,2] Irreversible changes to the vocal fold mucosa, such as scarring, atrophy, and sulcus vocalis, require regenerative technologies to stimulate a controlled regrowth of the tissue. An increasing number of biomaterial systems have been proposed with the concurrent capability of refilling and regenerating severely damaged or absent vocal fold mucosae in situ (see review on public health significance in the study by Green et al. [3] ).Notably, as the vocal folds are located at the narrowest point of the airway, adverse hostÀbiomaterial responses can impair upper airway patency and create life-threatening complications. For instance, 2À5% of patients were reported to have postoperative inflammatory reactions including edema, dysphonia, and dyspnea to injectable biomaterials derived from hyaluronic acid (HA). [4][5][6] Although the incidence is rare, severe airway reactions could lead to an emergency admission for intensive care and require intubation procedures for breathing support. [5,7] Inevitably, this immunemediated rejection response is detrimental to the longevity, performance, and integration of the biomaterial in the vocal fold mucosa.Upon biomaterial introduction into a host, the immune system quickly responds to the iatrogenic trauma and foreign

Unraveling the Relevance of Tissue‐Specific Decellularized Extracellular Matrix Hydrogels for Vocal Fold Regenerative Biomaterials: A Comprehensive Proteomic and In Vitro Study

“…The induction of macrophage polarization toward the M2 phenotype would provide key evidence toward the applicability of VF dECM hydrogels toward VF repair. [8,77] Rather than solely relying on proteomic analyses and the presence of remnant immunogenic proteins, these results should be used in combination with in vivo studies to predict the immune response.…”

“…Mammalian vocal folds (VFs) have unique ECM‐structural and mucosa‐immunological profiles that likely benefit from a tissue‐specific regenerative approach like dECM. [ 8–10 ] Mass spectrometry has aided in profiling the proteome of organs of interest by measuring the mass‐to‐charge ratio (m z −1 ) of fragmented proteins in the sample. For complex ECM profiles like VF, proteomic analyses are imperative to generate a deep understanding of the interaction between biological systems and biomaterials for bioengineering applications.…”

“…[15] To address this scalability challenge, large organs such as small intestinal submucosa (SIS) or urinary bladder matrix (UBM) have been used for the extraction of dECM in developing VF regenerative biomaterials. [8,16] The larger size of porcine SIS can generate a larger volume of material from a single batch for testing and gel production. Several dECM-derived scaffolds are already clinically approved including Cook Biotech's Biodesign from SIS and ACELL's Matristem UBM.…”

Polymethylmethacrylate injections for augmentation and strengthening of abdominal muscles: an experimental model

“…PMMA is used in cured solid form as bone cement, for treating bone fractures and osteomyelitis [3] and in the treatments of bone tumors [4]. PMMA microspheres suspended in gel form are used in injections to correct congenital and acquired deformities such as Scleroderma en coup de sabre [5], in vocal cord medialization [6], in tissue engineering for the manufacture of heart valves [7], for treating urinary and fecal incontinence and gastroesophageal reflux [8], for treating acne scars [9], and in subcutaneous and juxta-dermal collagen biostimulation obtaining satisfactory results, with low complication rates [10].…”

The life‐cycle and restoration of the human vocal fold

“…As seen in other scarring conditions, 10 treatment runs the risk of triggering recurrent fibrosis and initiating a vicious cycle of scar deposition. A range of novel therapies have been trialed that aim to break this cycle, 11 , 12 , 13 but most remain experimental and in instances where data is available involving human subjects, 14 , 15 randomized controlled trials are yet to be reported.…”