Acellular dermis

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Acellular dermis is a type of biomaterial derived from processing human or animal tissues to remove cells and retain portions of the extracellular matrix (ECM). These materials are typically cell-free, distinguishing them from classical allografts and xenografts, can be integrated or incorporated into the body, and have been FDA approved for human use for more than 10 years in a wide range of clinical indications. [1]

Contents

Harvesting and processing

All ECM samples originate from mammalian tissues, such as dermis, pericardium, and small intestinal submucosa (SIS). After explantation from the source, the ECM biomaterial retains some characteristics of the original tissue. The ECM tissues can be harvested from varying stages in the developmental stages in mammalian species such as human, porcine, equine, and bovine. Although they are similarly composed of fibril collagen, the microstructure, specific composition (including presence of non-collagenous protein and glycosaminoglycans and ratio of different types of collagen), physical dimensions and mechanical properties can differ. Depending on the developmental stage of the tissue during which harvesting occurred, the microstructure can vary within an organism. Additionally, keeping in mind the size and shape of the final tissue, the potential of the physical dimensions of the tissue of origin must be considered. [1]

Despite this “memory” of the ECM tissue, methods have been engineered so that these innate characteristics can be modified, saved or removed. [1] The modification process varies depending on the material used in clinical setting. Some ECM biomaterials undergo a modification that removes all the cells but leaves the remainder of the other ECM components called decellularization. Another process that can be introduced into the biomaterial is artificial crosslinking. Artificial crosslinking has been shown to stabilize reconstituted collagen, which can rapidly degenerate in vivo. [1] Although mechanical strength is gained, the artificial crosslinks that are added increase the chance for a host-cell rejection, due to its foreign origin. [2] Due to this complication, intentional crosslinking is no longer practiced as more recent advancements have been made that increase the lifespan of the collagen without the use of artificial stabilization. Finally, to ensure the ECM biomaterial is without infectious bacteria and viruses, most are terminally sterilized. This can include ethylene oxide (EO) gas, gamma irradiation, or electron beam (e-beam) irradiation as the sterilizing agent. [1]

Decellularized ECM biomaterials can be further processed into a fine powder and then lyophilized (freeze-dried). This powder can then be mixed with collagenase to form an ECM derived hydrogel (self-healing hydrogels). These hydrogels are then used in cell culture to help maintain cell phenotype and increase cell proliferation. Cells cultured on ECM hydrogels maintain their phenotype better than cells cultured on other substrates such as matrigel or type 1 collagen. [3] [4] Though hydrogels do not yet have direct clinical relevance, they have shown promise as a method of assisting in organ regeneration. [3] [4] [5]

Similarly, whole organs can be decellularized to create 3-D ECM scaffolds. These scaffolds can then be re-cellularized in an attempt to regenerate whole organs for transplant. This method works primarily for organs with a complex vasculature, as it allows detergent to be fully perfused through the material. [6]

Host/implant interactions

Wound healing of the skin and tendons is a complex coordinated process in the body that happens slowly over weeks or even years. A number of products in the market today aim to affect this process positively, although little data is available on their success. The majority of products are still in the development phases where the (often inflammatory) interactions between the host and the implanted devices are being assessed.

Implanted ECM biomaterials fall into two general categories based on how they interact with the host. Incorporating devices eventually allow the growth of cells and passage of blood vessels through the matrix, whereas nonincorporating biomaterials are encapsulated by a wall of fused macrophages. In nonincorporating biomaterials such as Permacol, an acellular porcine dermal implant for hernia repair, it is important that the material is not degraded or infiltrated by the immune system. [1] [7] Encapsulated biomaterials that are recognized as foreign can be degraded and/or rejected by the body and migrate to the outside of the body. In incorporated ECM biomaterials, infiltration by the immune system can occur in as few as seven days, leading to rapid degradation of the device volume. In the case of Graftjacket, an allograft from human dermis, the matrix is quickly populated by host cells as vasculature. The device itself decreased more than 60% in volume, and is replaced with host fibroblasts and macrophages. [1] [8]

Applications

ECM biomaterials are used to promote healing in a number of tissues, especially the skin and tendons. Surgimend, a collagen matrix derived from fetal bovine dermis, can trigger the healing of tendons (which do not heal spontaneously) in the ankle. This intervention can shorten healing time by almost half and allows the patient to return to full activity much sooner. [9] Open wounds, like tendons, do not spontaneously heal and can persist for long stretches of time. When ECM biomaterials are added in multiple layers to the ulcer, the wound begins to close quickly and generates host tissue. Although preliminary studies seem promising, little information is available on the success of and direct comparisons between different ECM biomaterial devices in human trials. [1]

Alloderm, an acellular dermis derived from the skin of donated cadavers, [10] [11] is used in reconstructive and dental surgeries. In gingival grafts, the acellular dermis is an alternative to tissue cut from the palate of the patient's mouth. [12] It has also been used for abdominal hernia repair, [13] and to rebuild resected turbinates in the treatment of empty nose syndrome. [14] Alloderm and other acellular dermal matrices are used routinely in implant based breast reconstruction after mastectomy for improved soft tissue coverage and thus decrease the risk of visible rippling, capsular contraction, implant malposition, bottoming out and implant exposure. [15]

The FDA has not approved any acellular dermal matrix products for use in implant-based breast reconstruction following surgery to remove a breast tumour, as the published literature suggests that some products may have high risk profiles. [16]

Examples

Related Research Articles

<span class="mw-page-title-main">Extracellular matrix</span> Network of proteins and molecules outside cells that provides structural support for cells

In biology, the extracellular matrix (ECM), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and biochemical support to surrounding cells. Because multicellularity evolved independently in different multicellular lineages, the composition of ECM varies between multicellular structures; however, cell adhesion, cell-to-cell communication and differentiation are common functions of the ECM.

<span class="mw-page-title-main">Tissue engineering</span> Biomedical engineering discipline

Tissue engineering is a biomedical engineering discipline that uses a combination of cells, engineering, materials methods, and suitable biochemical and physicochemical factors to restore, maintain, improve, or replace different types of biological tissues. Tissue engineering often involves the use of cells placed on tissue scaffolds in the formation of new viable tissue for a medical purpose, but is not limited to applications involving cells and tissue scaffolds. While it was once categorized as a sub-field of biomaterials, having grown in scope and importance, it can is considered as a field of its own.

<span class="mw-page-title-main">Wound healing</span> Series of events that restore integrity to damaged tissue after an injury

Wound healing refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue.

Cardiomyoplasty is a surgical procedure in which healthy muscle from another part of the body is wrapped around the heart to provide support for the failing heart. Most often the latissimus dorsi muscle is used for this purpose. A special pacemaker is implanted to make the skeletal muscle contract. If cardiomyoplasty is successful and increased cardiac output is achieved, it usually acts as a bridging therapy, giving time for damaged myocardium to be treated in other ways, such as remodeling by cellular therapies.

<span class="mw-page-title-main">Artificial skin</span> Material to regenerate or replace skin

Artificial skin is a collagen scaffold that induces regeneration of skin in mammals such as humans. The term was used in the late 1970s and early 1980s to describe a new treatment for massive burns. It was later discovered that treatment of deep skin wounds in adult animals and humans with this scaffold induces regeneration of the dermis. It has been developed commercially under the name Integra and is used in massively burned patients, during plastic surgery of the skin, and in treatment of chronic skin wounds.

Nano-scaffolding or nanoscaffolding is a medical process used to regrow tissue and bone, including limbs and organs. The nano-scaffold is a three-dimensional structure composed of polymer fibers very small that are scaled from a Nanometer scale. Developed by the American military, the medical technology uses a microscopic apparatus made of fine polymer fibers called a scaffold. Damaged cells grip to the scaffold and begin to rebuild missing bone and tissue through tiny holes in the scaffold. As tissue grows, the scaffold is absorbed into the body and disappears completely.

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The dermal equivalent, also known as dermal replacement or neodermis, is an in vitro model of the dermal layer of skin. There is no specific way of forming a dermal equivalent, however the first dermal equivalent was constructed by seeding dermal fibroblasts into a collagen gel. This gel may then be allowed to contract as a model of wound contraction. This collagen gel contraction assay may be used to screen for treatments which promote or inhibit contraction and thus affect the development of a scar. Other cell types may be incorporated into the dermal equivalent to increase the complexity of the model. For example, keratinocytes may be seeded on the surface to create a skin equivalent, or macrophages may be incorporated to model the inflammatory phase of wound healing.

Dermal fibroblasts are cells within the dermis layer of skin which are responsible for generating connective tissue and allowing the skin to recover from injury. Using organelles, dermal fibroblasts generate and maintain the connective tissue which unites separate cell layers. Furthermore, these dermal fibroblasts produce the protein molecules including laminin and fibronectin which comprise the extracellular matrix. By creating the extracellular matrix between the dermis and epidermis, fibroblasts allow the epithelial cells of the epidermis to affix the matrix, thereby allowing the epidermal cells to effectively join together to form the top layer of the skin.

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<span class="mw-page-title-main">Decellularization</span>

Decellularization is the process used in biomedical engineering to isolate the extracellular matrix (ECM) of a tissue from its inhabiting cells, leaving an ECM scaffold of the original tissue, which can be used in artificial organ and tissue regeneration. Organ and tissue transplantation treat a variety of medical problems, ranging from end organ failure to cosmetic surgery. One of the greatest limitations to organ transplantation derives from organ rejection caused by antibodies of the transplant recipient reacting to donor antigens on cell surfaces within the donor organ. Because of unfavorable immune responses, transplant patients suffer a lifetime taking immunosuppressing medication. Stephen F. Badylak pioneered the process of decellularization at the McGowan Institute for Regenerative Medicine at the University of Pittsburgh. This process creates a natural biomaterial to act as a scaffold for cell growth, differentiation and tissue development. By recellularizing an ECM scaffold with a patient’s own cells, the adverse immune response is eliminated. Nowadays, commercially available ECM scaffolds are available for a wide variety of tissue engineering. Using peracetic acid to decellularize ECM scaffolds have been found to be false and only disinfects the tissue.

Decellularization of porcine heart valves is the removal of cells along with antigenic cellular elements by either physical or chemical decellularization of the tissue. This decellularized valve tissue provides a scaffold with the remaining extracellular matrix (ECM) that can then be used for tissue engineering and valve replacement in humans inflicted with valvular disease. Decellularized biological valves have potential benefit over conventional valves through decreased calcification which is thought to be an immuno-inflammatory response initiated by the recipient.

<span class="mw-page-title-main">Biomesh</span> Surgical mesh from biomaterial

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References

  1. 1 2 3 4 5 6 7 8 Cornwell, K.G., Landsman, A., James, K.S. Extracellular Matrix Biomaterials for Soft Tissue Repair. Clin Podiatr Med Surg 26 (2009) 507–523 (Original Article)
  2. ↑ "Badylak S. "Host Response to Biomaterials"". Archived from the original on 2019-03-19. Retrieved 2015-04-19.
  3. 1 2 Wolf MT, et al. "A hydrogel derived from decellularized dermal extracellular matrix"
  4. 1 2 Sawkins MJ, et al. "Hydrogels derived from demineralized and decellularized bone extracellular matrix"
  5. ↑ Barker TH "The role of ECM proteins and protein fragments in guiding cell behavior in regenerative medicine"
  6. ↑ Faulk, Denver M.; Johnson, Scott A.; Zhang, Li; Badylak, Stephen F. (August 2014). "Role of the extracellular matrix in whole organ engineering". Journal of Cellular Physiology . 229 (8). Wiley-Liss: 984–989. doi:10.1002/jcp.24532. ISSN   0021-9541. PMID   24347365. Archived from the original on 2022-08-02. Retrieved 2024-03-29.
  7. ↑ Faulk DM, et al. "ECM hydrogel coating mitigates the chronic inflammatory response to polypropylene mesh."
  8. ↑ [Graft Jacket Archived 2016-03-09 at the Wayback Machine
  9. ↑ Tei Biosciences
  10. ↑ Naomi Freundlich for the New York Times. March 16, 2003 All of Me
  11. ↑ Kerry Howley for the LA Times. March 6, 2007 Big business in body parts
  12. ↑ Hirsch A, Goldstein M, Goultschin J, Boyan BD, Schwartz Z (2005). "A 2-year follow-up of root coverage using sub-pedicle acellular dermal matrix allografts and subepithelial connective tissue autografts". Journal of Periodontology. 76 (8): 1323–8. doi:10.1902/jop.2005.76.8.1323. PMID   16101365.
  13. ↑ Misra, S.; Raj, P. K.; Tarr, S. M.; Treat, R. C. (2008-06-01). "Results of AlloDerm use in abdominal hernia repair". Hernia. 12 (3): 247–250. doi:10.1007/s10029-007-0319-z. ISSN   1265-4906. PMID   18209948. S2CID   9919259.
  14. ↑ Leong, SC (Jul 2015). "The clinical efficacy of surgical interventions for empty nose syndrome: A systematic review". Laryngoscope. 125 (7): 1557–62. doi:10.1002/lary.25170. PMID   25647010. S2CID   206202553.
  15. ↑ Hinchcliff KM, Orbay H, Busse BK, Charvet H, Kaur M, Sahar DE. Comparison of two cadaveric acellular dermal matrices for immediate breast reconstruction: A prospective randomized trial. J Plast Reconstr Aesthet Surg. 2017 May;70(5):568-576. doi: 10.1016/j.bjps.2017.02.024. Epub 2017 Mar 6. PMID 28341592.
  16. ↑ "Acellular Dermal Matrix (ADM) Products Used in Implant-Based Breast Reconstruction Differ in Complication Rates: FDA Safety Communication". FDA. Retrieved 3 January 2023.
  17. ↑ Alloderm, manufactured by Lifecell
  18. ↑ SurgiMend and PriMatrix, manufactured by TEI Biosciences Inc. Archived 2016-07-10 at the Wayback Machine
  19. ↑ FDA 510k, Permacol
  20. ↑ Grafton, manufactured by Osteotech Inc. FDA 510K, Grafton
  21. ↑ FDA 510k, Orthadapt
  22. ↑ FDA 510k, Supple Peri-Guard
  23. ↑ Jayakumar, R; Chennazhi, KP; Srinivasan, S; Nair, SV; Furuike, T; Tamura, H (2011). "Chitin scaffolds in tissue engineering". Int J Mol Sci. 12 (3): 1876–87. doi: 10.3390/ijms12031876 . PMC   3111639 . PMID   21673928.
  24. ↑ Tissue Engineering: From Cell Biology to Artificial Organs, p163
  25. ↑ Ranganathan, Kavitha; Santosa, Katherine B.; Lyons, Daniel A.; Mand, Simanjit; Xin, Minqiang; Kidwell, Kelley; Brown, David L.; Wilkins, Edwin G.; Momoh, Adeyiza O. (2015-10-01). "Use of Acellular Dermal Matrix in Postmastectomy Breast Reconstruction: Are All Acellular Dermal Matrices Created Equal?". Plastic and Reconstructive Surgery. 136 (4): 647–653. doi:10.1097/PRS.0000000000001569. ISSN   1529-4242. PMID   26397242. S2CID   4769316.
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