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102 Dinaki et al. | Journal of Clinical and Translational Research 2024; 10(2): 99-111
Furthermore, the cells must be able to incorporate into the 4.4. Stem cells in TM regeneration
organ of Corti following injection and survive the potentially
lethal high potassium concentration of the endolymph [15,16]. The use of stem cells in regenerative techniques for TMP
Lee et al. evaluated the viability of human embryonic stem cells recovery has been studied in animal models [36]. Scaffold
(ESCs) in the cochlea of deaf guinea pigs preconditioned to have materials can be used as supporting structures to provide
low potassium levels [17]. Their study indicated that temporarily mechanical assistance and deliver cells for cell proliferation and
lowering the potassium concentration in the endolymph before differentiation. Combining scaffolds with MSCs or growth factors
transplantation, by flushing it with sodium caprate, contributed to has improved TPM healing efficacy. In two studies by Goncalves
a 1-week survival of human ESCs in the endolymph. et al., the combination of BM-MSCs with a HA scaffold or gelatin
Injecting genes and medications to rejuvenate the present cells sponge, respectively, resulted in enhanced TMP recovery [37,38].
of the inner ear is challenging. Researchers have already tested the In a clinical trial by Vozel et al., [11] patients were given
efficacy of the gene-editing technology CRISPR/Cas9 in treating autologous platelet- and extracellular vesicle-rich plasma as a
animal models with autosomal dominant hearing loss [18]. To therapy for persistent postoperative inflammation of the temporal
activate the existing cells, the future treatment will involve bone cavity. A persistent postoperative inflammation of the
combining stem cell therapy, gene therapy, and pharmacological temporal bone cavity is defined as a chronically discharging radical
therapy. In 2020, Huang et al. developed an induced pluripotent mastoid cavity that is oftentimes the result of a canal wall-down
stem cell (iPSC) line from a 7-year-old male patient with a mastoidectomy. The findings of the trial indicated the remarkable
homozygous GJB2 c.235delC mutation [19]. Human SOX2, efficacy of autologous platelet- and extracellular vesicle-rich
OCT4, KLF4, and c-MYC reprogramming factors were expressed plasma in treating persistent postoperative inflammation of the
in reprogrammed peripheral blood mononuclear cells. Five iPSC temporal bone cavity, thereby suggesting its promising use after
clones were manually selected, grown, and stored; their capacity conventional surgical and conservative therapies have been
to differentiate into three germ layers was revealed. Genetic exhausted [39].
technology can precisely regulate stem cells in vivo, ameliorating 4.5. Ossicles
their applicability in therapies.
Through tissue engineering, ossicle reconstruction is performed
4.2. Tympanic membrane (TM) by cultivating MSCs on bioresorbable 3D scaffolds. Danti et al.

The TM is a thin membrane between the external and middle developed partial ossicular replacement prosthesis (PORP)-like
ear. TM perforations (TMPs) are a significant issue in otology. scaffolds with a biocompatible and biodegradable polymer [47].
While acute TMPs can heal naturally, chronic TMPs require The poral characteristics were analyzed using micro-CT, and
surgery (i.e., tympanoplasty). The standard surgical procedure is the capacity to support human MSC (hMSC) colonization and
performed through tympanoplasty, using the perichondrium or osteoblastic development in vitro was analyzed quantitatively
temporalis fascia to rectify the TMP. In regenerative therapy, a and qualitatively [48]. The findings demonstrated that the
range of scaffold materials (e.g., hyaluronic acid [HA], collagen, poral characteristics of PORP-shaped scaffolds were necessary
chitosan, and gel foam), growth factors, and cells have been used to support the colonization of hMSCs and their osteoblastic
as therapies for TMP (Table 3). maturation in vitro.
4.3. Growth factors in TMP regeneration 4.6. Cartilaginous craniofacial components
Growth factors have been studied for the repair of TMPs. Autologous cartilage is the gold standard for nasal and
A randomized controlled trial conducted by Lou and Lou auricular reconstruction. However, the use of allogenic and
included 184 patients with traumatic TMP [32]. The intervention synthetic materials for the cartilage is known to increase the risk
groups received drops containing EGF, FGF-2, and ofloxacin, of tissue rejection, resorption, extrusion, and infection. In this
respectively [32]. The study reported that all treatment groups regard, regenerative engineering methods may be preferred as the
had significantly shorter closure times than the control group. engineered cartilages closely resemble native cartilages and can
A randomized controlled trial with 93 study subjects treated with be produced in large amounts. In addition, these cartilages can be
basic fibroblast growth factor (bFGF) displayed a substantially specifically shaped by harvesting cartilage cells from the auricle
higher closure rate and a considerably shorter closure time in or septum and growing them in a specific 3D scaffold. Likewise,
the experimental group than in the control group [33]. Cai et al. growth factors can facilitate the growth and differentiation of the
examined the short- and long-term detrimental effects of fibroblast cartilage cells in the scaffold.
growth factor-2 (FGF-2) therapy in 134 patients with tympanic In 2004, autologous cultured chondrocytes were utilized
perforations. The results revealed that the total closure rate and the in human nose reconstruction for the first time [49]. Yanaga
closure healing duration were much better in the FGF-2 group [34]. et al. extracted the chondrocytes from the conchal cartilage and
Kanemaru et al. investigated the use of fibrin glue and gelatin sponge cultivated them in vitro. The chondrocytes were then injected into a
with bFGF, the use of which demonstrated increased healing rates subcutaneous pocket above the nasal bone. No complications were
of complete TMP closure as compared to the control group [35]. reported after a 2-year follow-up period. In 2009, Yanaga et al.

DOI: https://doi.org/10.36922/jctr.22.00151