Figure 3 - available via license: CC BY-NC-SA
Content may be subject to copyright.
Cryopreserved birth tissue products in ophthalmology: (a) Cryopreserved amniotic membrane was the first birth tissue product on the market. (b) The cryopreserved umbilical cord product (AmnioGuard) was available in 2010. The PROKERA family of devices comprises four models (c-f) of a biologic corneal bandage. (c) The PROKERA is designed such that an amniotic membrane is clipped to a dual polycarbonate ring system, allowing the membrane to act as a biological bandage when in contact with the cornea. (f) PROKERA PLUS model has two amniotic membrane layers, providing extra therapeutic benefit. (d) PROKERA SLIM and (e) PROKERA CLEAR both have a thinner, smaller ring (less plastic), while (e) PROKERA CLEAR also provides central aperture clearance d c
Source publication
The birth tissue is predominantly comprised of amniotic membrane (AM) and umbilical cord (UC), which share the same cell origin as the fetus. These versatile biological tissues have been used to treat a wide range of conjunctival and corneal conditions since 1940. The therapeutic benefits of the birth tissue stem from its anti-inflammatory and anti...
Context in source publication
Context 1
... thickness of the UC product is approximately 500-900 µm compared to 75-150 µm for the AM product. [13] These cryopreserved products [ Figure 3] can be stored for 2 years (from the manufacturing date) at temperatures ranging from − 80°C to 4°C. Both cryopreserved AM and UC have been used clinically in ophthalmology to treat indications such as keratitis, band keratopathy, burns, keratoconjunctivitis, ulcers, basement membrane dystrophy, LSCD, epithelial defects, corneal erosion, Stevens-Johnson syndrome, and toxic epidermal necrolysis. ...
Citations
... They have been shown to orchestrate regenerative healing within its anti-inflammatory and anti-scarring properties in ophthalmic applications. (6) Interestingly, FLO appears to relieve pain effectively in several ocular surface disorders, (7)(8)(9) and musculoskeletal disorders such as osteoarthritis (10,11) and lower extremity neuropathy. (12) However, the mechanisms underlying their pain inhibition properties remain unknown. ...
Pain after surgery causes significant suffering. Opioid analgesics cause severe side effects and accidental death. Therefore, there is an urgent need to develop non-opioid therapies for managing post-surgical pain and, more importantly, preventing its transition to a chronic state. In a mouse model of post-surgical pain, local application of Clarix Flo (FLO), a human amniotic membrane (AM) product, attenuated established post-surgical pain hypersensitivity without exhibiting known side effects of opioid use in mice. Importantly, preemptive drug treatment also inhibited the transition of post-surgical pain to a prolonged state. This effect was achieved through direct inhibition of nociceptive dorsal root ganglion (DRG) neurons via CD44-dependent pathways, and indirect pain relief by attenuating immune cell recruitment. We further purified the major matrix component, the heavy chain-hyaluronic acid/pentraxin 3 (HC-HA/PTX3) from human AM that has greater purity and water solubility than FLO. HC-HA/PTX3 replicated FLO- induced neuronal and pain inhibition. Mechanistically, HC-HA/PTX3 induced cytoskeleton rearrangements to inhibit sodium current and high-voltage activated calcium current on nociceptive neurons, suggesting it is a key bioactive component mediating pain relief. Collectively, our findings highlight the potential of naturally derived biologics from human birth tissues as an effective non-opioid treatment for post-surgical pain and unravel the underlying mechanisms.
... The amniotic fluid consists of several layers. Basal layer, compact layer, fibroblastic layer, and spongy layer, which is a source of important MSCs (Tighe et al. 2020;Zavatti et al. 2020). According to previous research, avian Amniotic Mesenchymal Stem Cells (AMSCs) are obtained from the amniotic spongy layer of 8-day-old chicken embryos and 14-day-old Beijing duck embryos (Li et al. 2014). ...
... Studies show that in groups treated with laser, a higher amount of collagen is produced, which leads to wound closure. Also, the amount of immune cell secretion was higher in the irradiated group, which helped wound healing (8). In addition to these studies, laser treatment can affect controlling inflammation by reducing edema (9). ...
Background: Fibroblasts are the most important cells in the healing process of wounds. The motility activity of low-level laser (light) therapy (LLLT) on fibroblast proliferation has been well-established in vitro. Laser treatment for scar removal increases the number of scars. Objectives: This method uses light therapy to remove the outer layer of the skin surface and produce new skin cells to cover the damaged skin cells. Methods: The present research is from an experimental laboratory. First, tissue fibroblast cells were cultured under appropriate conditions. Then, it was exposed to laser radiation with intensities of 650 and 980 nm, and its supernatant solution was used for wound treatment. Interleukin 2 (IL-2), tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF) levels were used to check the recovery. Results: The results of the MTT assay showed an increase in the viability of the cell line under laser irradiation. In addition, these evaluations showed an increase in IL-2, TNF-α, and VEGF after 650 and 980 nm laser irradiation compared to the control group after 48 hours. Conclusions: According to the present study, laser therapy has potential therapeutic potential for wound healing. However, more studies are suggested to increase the efficiency and speed up the treatment process.
... Sutureless cAM covers and protects the corneal surface while promoting corneal healing through its anti-inflammatory and anti-scarring properties that support epithelial adhesion and differentiation. 3,4 When used in patients with severe DED, cAM has been shown to significantly improve the ocular surface health and symptoms for up to 6 months. [5][6][7][8][9] In one prospective, randomized study, treatment with cAM for 3-5 days resulted in a significant improvement in dry eye severity score, corneal staining, tear break-up time, and corneal nerve density in DED patients at 1 and 3 months, whereas control subjects receiving conventional maximum treatment showed no significant change. ...
Background
While sutureless, cryopreserved amniotic membrane (cAM) has been shown to significantly improve signs and symptoms of dry eye disease (DED), no studies have assessed the association of cAM treatment duration to the differential response in clinical outcomes.
Methods
A multi-center, retrospective study was conducted on patients with moderate-to-severe DED who were treated with self-retained cAM (Prokera® Slim) for 2 to 7 days. The primary outcome measure was DEWS severity score assessed at 1 week, 1 month, and 3 months. Secondary outcome measures included ocular discomfort, visual symptoms, corneal staining, and visual acuity.
Results
A total of 89 eyes (77 patients) with moderate-to-severe DED (DEWS severity 3.24 ± 0.56) received treatment with self-retained cAM for 2 days (n = 10), 3 days (n = 15), 4 days (n = 12), 5 days (n = 19), 6 days (n = 6), or 7 days (n = 27). DEWS scores significantly improved at 1 week, 1 month, and 3 months for all treatment duration groups, with no significant difference observed between groups at any timepoint. In addition to an improvement in DEWS severity scores, those receiving cAM treatment for 2 days demonstrated a significant improvement in corneal staining, visual symptoms, and ocular discomfort at 1 week, 1 month, and 3 months.
Conclusion
This retrospective study suggests that a single placement of self-retained cAM for 2 days can significantly improve signs and symptoms of DED with a lasting benefit observed for up to 3 months.
... Collagen production by fibroblasts provides structural stability and reduces wound size. Although collagen and glycosaminoglycan's assembly in the early phase of wound repair is crucial for a proper healing process, it could lead to an irregular fibril arrangement and fibrosis [57]. Liver fibrosis which is caused by various inducers such viral hepatitis, excessive alcohol consumption, and fat deposition can lead to liver dysfunction and failure, and an enhanced risk of liver malignancies [58,59]. ...
... Incubation of HSCs with hAM-derived exosomes results in a significant prohibition of TGF-β1-activated HSCs, inhibition of HSC migration, and profound down-regulation in the expression of fibrosis-associated genes such as α smooth muscle actin (ACTA) [68]. AME is able to reverse the myofibroblasts phenotype into fibroblasts and to inhibit fibrosis [69], an effect mostly attributed to HC-HA/PTX3-mediated TGF-β1 suppression [57]. Such a role of HC-HA/PTX3 is mediated by an upregulation of the expression of BMP-4, BMP-6, BMP receptor1A (BMPR1A), BMPR1B, and BMPR2 consequently to the activation of stromal cell derived factor-1/C-X-C chemokine receptor type 4 (SDF-1/CXCR4) signaling [70]. ...
Liver is a vital organ responsible for metabolic and digestive functions, protein synthesis, detoxification, and numerous other necessary functions. Various acute, chronic, and neoplastic disorders affect the liver and hamper its biological functions. Most of the untreated liver diseases lead to inflammation and fibrosis which develop into cirrhosis. The human amniotic membrane (hAM), the innermost layer of the fetal placenta, is composed of multiple layers that include growth-factor rich basement membrane, epithelial and mesenchymal stromal cell layers. hAM possesses distinct beneficial anti-fibrotic, anti-inflammatory and pro-regenerative properties via the secretion of multiple potent trophic factors and/or direct differentiation into hepatic cells which place hAM-based therapies as potential therapeutic strategies for the treatment of chronic liver diseases. Decellularized hAM is also an ideal scaffold for liver tissue engineering as this biocompatible niche provides an excellent milieu for cell proliferation and hepatocytic differentiation. Therefore, the current review discusses the therapeutic potential of hAM and its derivatives in providing therapeutic solutions for liver pathologies including acute liver failure, metabolic disorders, liver fibrosis as well as its application in liver tissue engineering.
... For more than 110 years, amniotic membranes (AM) have been used in various applications such as managing wounds of the skin or cornea surface and supplementing damaged joints or tendons [4][5][6]. The therapeutic potential of AM inpart is thought to be due to its composition of extracellular matrix components that have been shown to be important for modulating inflammation and tissue regeneration in the wound healing process [7,8]. ...
Background
Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by symptomatic frequency and urgency, as well as chronic pelvic pain. Disruption of the urothelial barrier is closely associated with IC/BPS. As amniotic membranes (AM) offer capabilities of wound healing in many other fields of medicine, likewise amniotic bladder therapy (ABT) may offer capability of urothelial healing in IC/BPS.
Methods
Under general anesthesia, 10 consecutive IC/BPS patients received intra-detrusor injections of 100 mg micronized AM (Clarix Flo) diluted in 10 ml 0.9% preservative-free sodium chloride. Clinical evaluation and questionnaires (Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS), Overactive Bladder Assessment Tool, and SF-12 Health Survey) were repeated at pre-op and 2, 4, 8 and 12 weeks post-op.
Results
Ten females (47.4 ± 14.4 years) who had recalcitrant IC/BPS for 7.8 years (5.2–12.1 years) received injection of micronized AM uneventful in all cases. After treatment, voiding symptoms and bladder pain significantly improved from pre-injection to 3 months. BPIC-SS significantly decreased from 37.4 ± 0.70 at baseline to 12.2 ± 2.90 at 3 months (p < 0.001). This corresponded to a significant improvement in their overall physical and mental quality of life. No adverse events occurred related to micronized AM injections, such as UTIs or acute urinary retention.
Conclusion
ABT could be an innovative treatment option for IC/BPS patients in terms of improving clinical symptoms based on preliminary outcomes at 3 months. Further studies are warranted to confirm the usefulness of ABT in patients with IC/BPS and to determine the duration of the effect.
... The umbilical cord patch (UCP) has emerged as a novel technique for reconstructing corneal perforations and descemetoceles [11,12]. It is easier to manipulate and has been successfully used for tube shunt coverage and conjunctival surface reconstruction [13]. The UCP contains a high concentration of biological signaling agents, such as high molecular weight hyaluronic acid, heavy chain-hyaluronic acid complex, and pentraxin 3, which are recognized as the most important factors underlying the anti-inflammatory, anti-scarring, and antiangiogenic effects of the UCP [4]. ...
Background:
Umbilical cord patch (UCP) grafts have been successfully used for glaucoma shunt tube coverage and conjunctival surface reconstruction. In recent years, the technique has emerged as a novel alternative for the reconstruction of corneal perforation and descemetocele. This study aimed to evaluate the effectiveness of combined UCP grafting and human amniotic membrane (HAM) transplantation for the management of corneal perforation or descemetocele.
Methods:
This prospective, non-comparative, interventional case series included nine eyes of nine patients with corneal descemetoceles and 28 eyes of 28 patients with corneal perforations, all in a clinically quiescent state. UCP grafting and HAM transplantation were combined to treat all patients. We re-examined the patients daily throughout the first week, weekly for 1 month, and then monthly for the first 6 months using slit-lamp examination and anterior segment optical coherence tomography.
Results:
We included 37 eyes with descemetocele or corneal perforation in a clinically quiescent state. The mean (standard deviation) ages of patients with corneal descemetocele and corneal perforation were 56.3 (18.8) years and 54.3 (18.1) years, respectively. The male-to-female ratios in patients with corneal descemetocele and corneal perforation were 56% to 44% and 61% to 39%, respectively. Postoperative corneal thickness increased significantly in eyes with descemetocele compared to preoperative values (P < 0.001). Postoperative best-corrected distance visual acuity improved significantly compared to preoperative values in eyes with descemetocele or corneal perforation (both P < 0.001), with relief of accompanying ocular symptoms. We did not observe any recurrence or complications such as rejection, infection, suture-related problems, or severe inflammation and all had a formed anterior chamber up to the final follow-up visit.
Conclusions:
Combined UCP grafting and HAM transplantation could be a promising alternative treatment for corneal perforation or descemetocele in clinically quiescent eyes, providing satisfactory reconstruction and functional outcomes. Further studies with robust designs, larger sample sizes, and longer follow-up are needed to verify the efficacy and safety of this modified surgical technique in enhancing vision and restoring anterior segment anatomical integrity in compromised corneas.
... MSC-secreted TSG-6 catalyzing HC transfer to HA and HA crosslinking enables the formation of cable-like hyaluronan raft that traps inflammatory cells and has a pivotal role in suppressing inflammation [41,106]. Administration of HC-HA-PTX3 isolated from the amniotic membrane displays anti-inflammatory, anti-fibrotic, and pro-regenerative effects, which was demonstrated by its ability to prolong the lifespan of a mismatched corneal allograft in mice by suppressing CD4 + Th1 cells and macrophages [107,108]. ...
Since their inception in the 1960s-70s, mesenchymal stem/stromal cells (MSCs) have gained interest because of their differentiation potential, anti-inflammatory effects, and immune-modulating properties. Both cell-based and cell-free MSC treatments show healing capacity in injured tissues. Cell-based treatment comprises MSCs and all secreted products, whereas cell-free treatments include only the secreted products. MSCs are therapeutically administered to many damaged organs owing to their efficacy. Specifically, the eye is a unique organ system to study the effects of MSCs, as treatment is easily applied and measured owing to its external location. The eye holds an immune-privileged status, wherein inflammation and immune responses are innately down-regulated. As excessive inflammation in the cornea often leads to fibrosis and irreversible corneal hazing, many studies have investigated the anti-inflammatory and immune-modulating capacities of MSCs. Decades of research suggest that MSCs modulate the immune response by secreting cytokines, growth factors, and extra-cellular matrix proteins that inhibit the infiltration of inflammatory cells following injury and promote a healing phenotype via M2 macrophage polarization. MSCs have also shown trans-differentiation potential into cornea-specific cell types during the wound healing process, such as corneal epithelial, stromal, or endothelial cells. This review discusses recent investigations of MSC treatment in the cornea, focusing on therapeutic efficacy, mechanisms, and future directions.
... Furthermore, amniotic scaffold reduced fibrosis and induced formation of organized muscle through its growth factors and cytokines. [27][28][29] CONCLUSIONS AMS may have the ability to promote muscle regeneration by exerting a paracrine effect on the host to regenerate polarized, structural muscle. This study serves as a proof of concept that AMS may be a promising, clinically feasible strategy that deserves further investigation for the treatment of VML defects. ...
Current treatment for volumetric muscle loss is limited to muscle transfer or acellular collagen scaffold (ACS) therapies that are associated with donor site morbidity and nonfunctional fibrosis, respectively. The aim of this study is to assess the utility of amniotic membrane scaffold (AMS) for volumetric muscle loss treatment.
Methods:
Murine quadriceps defects were created and randomized to three groups (n = 5/group): untreated controls, ACS, and AMS. In vivo muscle regeneration volume was quantified by MRI and microcomputed tomography. Muscle explants were analyzed using standard histology and whole-mount immunofluorescence at 8 weeks.
Results:
The cross-sectional muscle regeneration ratio was 0.64 ± 0.3 for AMS, 0.48 ± 0.07 for ACS, and 0.4 0 ± 0.03 for controls as assessed by MRI (P = 0.09) and 0.61 ± 0.28 for AMS, 0.50 ± 0.06 for ACS, and 0.43 ± 0.04 for controls as assessed by microcomputed tomography (P = 0.2). Histologically, AMS demonstrated significantly higher cellular density (900 ± 2 70 nuclei/high powered field) than ACS (210 ± 36) and control (130 ± 4) groups (P = 0.05). Immunofluorescence for laminin (AMS 623 ± 11 versus ACS 339 ± 3 versus control 115 ± 7; P < 0.01) and myosin heavy chain (AMS 509 ± 7 versus ACS 288 ± 5 versus control 84 ± 5; P = 0.03) indicated greater organized muscle fiber formation with AMS.
Conclusion:
AMS mediated muscle healing was characterized by increased cellular infiltration and organized muscle formation when compared with controls and ACS.
... By contrast, the self-adhesive amniotic membrane used in this study is a dehydrated membrane. Preservation methods have a significant effect on the structural and biochemical characteristics of amniotic membranes [16][17][18]. ...
... The healing, anti-inflammatory, and regenerative properties of amniotic membranes come from their biological activity, which can be largely attributed to the heavy chain hyaluronic acid pentraxin (HC-HA/ PTX3) complex [19]. The heavy chain component, HC-HA, was found to have many anti-inflammatory characteristics including antiangiogenic properties, making it crucial for the therapeutic efficacy of amniotic membranes [17]. Membranes dehydrated with heat were found to lack the HC-HA component potentially due to compaction of stromal and chorion layers [18]. ...
Purpose
Pterygium is a non-cancerous, fibrovascular growth of the bulbar conjunctiva that can cause visual disturbance, ocular pain, and cosmetic concerns. Surgical management is required in certain cases, which consists of excising the pterygium and associated Tenon’s, then overlaying the bare sclera with an autograft or amniotic membrane using glue or sutures. The purpose of this study is to assess outcomes of pterygium repair using a newly developed self-adhesive amniotic membrane that does not require glue or sutures for fixation.
Methods
Chart review of pterygium excision using a new self-adhesive amniotic membrane from a single surgical practice from 2012-2018. Descriptive statistics from 51 primary cases of pterygium excision were included.
Results
Pterygium recurrence occurred in 3 of the 51 self-adhesive amniotic membrane cases studied, resulting in a recurrence rate of 5.9%. Pterygium excision with the self-adhesive amniotic membrane had high rate of pyogenic granuloma formation of 27%. Self-adhesive amniotic membranes were found to perform comparably to more widely used techniques for pterygium excision, namely amniotic membranes and conjunctival autographs with glue or sutures. However, the self-adhesive grafts are associated with substantially more pyogenic granuloma formation.
Conclusion
Self-adhesive amniotic membranes offer comparable efficacy for preventing pterygium recurrence in comparison to other amniotic membranes and the conjunctival autograft. The incidence of pyogenic granuloma formation is higher in self-adhesive grafts compared to other widely used options.
