Allogeneic Cultured Keratinocytes and Dermal Fibroblasts in Murine Collagen

Overview

Allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen are cellularized scaffolding materials used to treat individuals with surgically treated thermal burns. It was created as an alternative to autografting, which involves harvesting and grafting skin from a patient onto the burn site. Allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen are a bi-layered construct comprising two lab-grown skin cells: keratinocytes and dermal fibroblasts. Human growth hormones, cytokines, and extracellular matrix proteins needed in wound repair are delivered to the burn site by sheets containing this scaffold product. The product is not permanently engrafted and is gradually replaced by the patient's cells, lowering or eliminating the necessity for autografting. In June 2021, the Food and Drug Administration (FDA) accepted the usage of allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen.

Drug Group

Allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen belong to a biotech drug that supports the formation of new tissue using allogeneic cellularized scaffold materials containing donor cells. It belongs to the biological category of cell transplant therapies.

Indications

An allogeneic cellularized scaffolding containing allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen can be used for the treatment of adults with deep partial-thickness burns (thermal burns comprising intact dermal elements in cases where surgical intervention is considered necessary).

Contraindications

Patients with known allergies to murine collagen or products containing bovine- or porcine-derived components should avoid using this medicine.

Dosage Forms and Available Strengths

Allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen are a 15.5 square inches (about 3.15 inches by 4.92 inches) pale white rectangular sheet containing a viable, bioengineered, allogeneic cellularized scaffolding material obtained from keratinocytes developed on gelled collagen comprising cutaneous fibroblasts.

Warnings and Precautions

• Potential Sensitivity: In murine collagen, Glycerin is present in allogeneic cultured keratinocytes and dermal fibroblasts. Patients with known sensitivity (allergic reaction) to Glycerin should avoid using it.

• Reactions to Hypersensitivity: There is a risk of severe hypersensitivity reactions to allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen. Following the application of allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen, look for early and late symptoms and warning signs of hypersensitivity responses and treat these reactions according to established medical protocol.

• Infectious Disease Transmission: Allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen contain human donor cells and may transfer infectious diseases or infectious agents, such as viruses, bacteria, or other pathogens, like the agent causing transmissible spongiform encephalopathy (TSE, also known as Creutzfeldt-Jakob disease (CJD) or variant CJD) (a set of progressive, incurable, and fatal illnesses caused by prions that damage the brain and nervous system in various animals, especially humans, cattle, and sheep). Allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen, a xenotransplantation material (the act of transferring nonhuman animal cells, tissues, or organs into human recipients or through ex vivo interactions with human body fluids), were previously exposed to well-characterized mouse cells. The cell banks have been evaluated and proven to be free of detectable adventitious agents, and mouse cells are no longer employed in the production of allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen; nonetheless, these precautions do not eliminate the risk of infectious diseases and disease agents being transmitted. Allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen have not been linked to transmitting infectious diseases or agents.

• Blood, Organs, Tissues, or Cell Donation: Allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen recipients should refrain from donating the whole blood, components of the blood, tissues, breast milk, eggs, sperm, or other body parts for use in humans because this is a xenotransplantation medicine.

For Patients

What Are Deep Thermal Burns?

Deep thermal burns are a form of burn injury affecting the epidermis and some of the skin's dermis. Burns are commonly produced by contact with a hot object, such as boiling water, a hot cooktop surface, or steam from an iron. The depth of thermal injury is proportional to the contact temperature, time of contact with the external heat source, and skin thickness. Deep thermal burns can cause pain, blisters, swelling, and skin color changes to red, white, or charred (blackened). Deep, extensive burns can result in life-threatening consequences such as shock and severe infections. People with severe burns might need intravenous fluids, surgery, and rehabilitation, which is generally done at a burn center.

How Do Allogeneic Cultured Keratinocytes and Dermal Fibroblasts in a Murine Collagen Work?

Allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen is a bioengineered, cellularized scaffolding material used to help repair deep thermal burns. It comprises laboratory-grown skin cells, keratinocytes, and dermal fibroblasts cultivated on a murine collagen matrix, creating a bi-layered construct. These cells are metabolically active and viable, allowing these cells to grow and function. When these cells are introduced to the burn site, these cells release human growth factors, cytokines, and extracellular matrix proteins that aid in wound healing. Allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen are not permanently engrafted. Still, they are gradually replaced by the patient's cells, thereby minimizing or eliminating the need for autografting, which results in a fresh wound at the location from which the graft is removed. This provides a short-term, actively functioning skin substitute that promotes healing and tissue regeneration as an alternative to autografting.

What Are the Clinical Uses of Allogeneic Cultured Keratinocytes and Dermal Fibroblasts in Murine Collagen?

This allogeneic cultured product aids healing by incorporating cells that secrete human growth factors, cytokines, and extracellular matrix proteins. This promotes tissue healing and decreases scarring (a tissue growth that marks the location where the skin has healed following an injury). Allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen were created as an alternative to autografting, which causes new wounds at the graft site. It provides long-term wound closure, similar to autograft results. This product is intended to integrate into the clinical process, making it easier for healthcare providers to use. It may also lessen or eliminate the requirement for skin harvesting for grafting. However, seeking specific medical advice from a healthcare expert is critical.

How Are Allogeneic Cultured Keratinocytes and Dermal Fibroblasts in Murine Collagen Administered?

• Preparation: Allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen is a wound healing treatment that covers huge wound regions with an off-white rectangle. In a surgical setting, it is prepared using a laminated foil bag, allogeneic cultured keratinocytes, dermal fibroblasts in a murine collagen product dish, and a polystyrene insert tray. One construct requires two operators, and numerous constructs should be created in batches. The complete treatment takes approximately 20 minutes. Warm the hold solution bottle in a warming oven or water bath before presenting it to the sterile operator for placement in the sterile field. Using forceps or gloved fingers, the sterile operator takes the allogeneic cultured keratinocytes and dermal fibroblasts in the murine collagen insert tray from the allogeneic cultured keratinocytes and dermal fibroblasts in the murine collagen product dish. Maintain the allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen construct in the hold solution for 15 minutes to four hours, moistening the meshes or tissue board as required.

• Administration: It is administered by a trained healthcare provider under aseptic conditions. Apply fibrin glue to the wound bed before applying the meshed allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen. Place the allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen on the patient's wound bed, with the dermal side down and the epidermal side facing up. If the region is smaller than one build, remove any extra allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen. Make sure allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen are in contact with the entire wound bed surface and that it is not stretched or expanded. To keep allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen in place, use staples, tissue adhesives, or sutures. Place a nonadherent contact dressing over allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen for one week before changing it. Place a second layer of dressing on top of the first. A therapeutically acceptable outer bolster or wrap can be used.

What Are the Side Effects of Allogeneic Cultured Keratinocytes and Dermal Fibroblasts in Murine Collagen?

Itchiness (pruritus), blisters (a painful condition that occurs when fluid fills a gap between skin layers), hypertrophic scarring (a raised, thick scar), and poor healing were the most prevalent side effects (incidences greater than two percent).

What Are the Things to Inform the Doctor Before Taking Allogeneic Cultured Keratinocytes and Dermal Fibroblasts in Murine Collagen?

It is critical to inform the doctor about the following before using allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen:

• Tell the doctor if patients have known allergies to murine collagen or goods containing bovine or porcine components.

• Allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen contain Glycerin, which makes it sensitive. Notifying the physician if patients have a known sensitivity (irritant reaction) to Glycerin is critical.

• Make sure the doctor is aware of all the drugs patients are currently taking. For example, after using allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen, it is not suggested to use Mafenide acetate.

• If patients are pregnant or plan to become pregnant, see the physician. There is no data on allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen use in pregnant women.

Storage and Handling:

• Allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen should be stored between -70 degrees Celsius (°C) and -90 degrees Celsius (-94 degrees Fahrenheit to -130 degrees Fahrenheit).

• The hold solution should be stored between 2 degrees Celsius and 8 degrees Celsius (36 degrees Fahrenheit and 46 degrees Fahrenheit).

• Keep the hold dishes at room temperature.

• If any of the components mentioned earlier have been compromised, do not use it.

• Unused allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen should be disposed of as surgical biohazardous waste, following local regulations.

• Materials that have come into touch with allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen should be disposed of as surgical biohazardous waste per local regulations.

For Doctors

Pharmacodynamics

Allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen's pharmacodynamic effects are unknown.

Mechanism of Action

A cellularized allogeneic scaffold product containing metabolically active cells that generate and secrete several growth factors and cytokines. This product secretes human growth factors and cytokines and contains human extracellular matrix proteins, according to in vitro investigations. Wound repair and regeneration are known to be aided by growth hormones, cytokines, and extracellular matrix proteins. This product is never permanently engrafted but is gradually replaced by the patient's cells, eliminating or lowering the requirement for autografting in most treated wounds. At three months, 85 patients in Studies 1 and 2 were assessed for the persistence of allogeneic scaffold product DNA at the treatment site. Allogeneic scaffold product-related DNA was not found in these cases.

Pharmacokinetics

Allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen's pharmacokinetic effects are unknown.

Drug Interactions

• Mafenide Acetate: It is not recommended to utilize Mafenide acetate after using allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen. This topical antibiotic has been proven to impair keratinocyte viability and compromise the structural integrity of tissue-engineered human skin replacements made of primary keratinocytes.

• Dressings and Antimicrobials Containing Silver: The application of silver-containing antimicrobials or dressings is not advised since in vitro studies indicate that silver may reduce the longevity of keratinocytes and human skin fibroblasts.

• Chlorhexidine: Applying an antimicrobial Chlorhexidine solution to the wound is not recommended after applying allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen. Keratinocytes and human dermal fibroblasts have been proven toxic to this substance.

Clinical Studies

This allogeneic cultured product's efficacy in adult patients with thermal burns containing intact skin elements was studied in two randomized, open-label, multicenter clinical studies. This significantly reduced pain and scarring at possible donor sites, according to study 1, and 83 percent of patients achieved lasting wound closure at three months without autograft insertion. The findings were consistent across race, ethnicity, gender, age, burn size, this allogeneic cultured product treatment area, and Baux score subgroups.

In Study 2, 30 adult patients with severe thermal burns were given three to 49 percent of their total body surface area. The efficiency of wound treatment with this allogeneic cultured product was evaluated. At 6 and 12 months, 93.1 percent of allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen and 100 percent autograft sites had complete wound healing.

Specific Considerations

• Pregnancy: Due to an absence of data on animal reproductive and developmental toxicity studies, the usage of this allogeneic cultured product in pregnant women is unknown. However, in the general population of the United States, the estimated background risk of severe birth abnormalities and miscarriage is between two and four percent and fifteen and twenty percent, respectively.

• Breastfeeding: The presence of this allogeneic cultured product in human milk is unknown, as are its effects on breastfed infants and milk production. Breastfeeding benefits should be weighed against the mother's clinical necessity and potential adverse effects.

• Pediatric Use: The safety and effectiveness this allogeneic cultured product in pediatric patients (less than 18 years) have yet to be established.

• Geriatric Use: In Study 1, eight individuals aged 65 and older were included, and no changes in safety or efficacy were seen between senior and younger patients. The number of elderly patients, however, was insufficient to assess their response.