TABLE 3.
List of approved tissue-engineered products (TEPs).
| No. | Trade name/proper name | Manufacturer | Indications | Approvedby/date | Dosage | Product form | Description | AT/AL | Price |
| 1 | Apligraf (Organogenesis Inc., 2019c, 2020) | Organogenesi, Inc. and Novartis AG (United States) | Chronic VLU, DFU | US FDA 2000 June | Circular disk with a diameter and thickness of 75 and 0.75 mm in size | Bag | Bi-layer bioengineered skin with inner layer of HDFn and outer layer of HEKn | AL | $1,500–2500 per treatment |
| 2 | Dermagraft (Organogenesis Inc., 2019d) | Organogenesis, Inc. (United States) | Full-thickness DFU > 6 weeks extended through the dermis without tendon, muscle, joint capsule, or bone exposure | US FDA 2001 September | 2 × 3-inch sheets | Bag | Fibroblasts on a piece of bio-absorbable scaffold | AL | $1,700 per treatment |
| 3 | Aurix (Napodano, 2015; Nuo Therapeutics Inc., 2019) | Nuo Therapeutics, Inc. (United States) | All types of ulcers (DFU, pressure, VLU, etc.) | US FDA 2007 September | Depends on the size and condition of the wound | Gel | PRP hematogel | AL | $430 per treatment |
| 4 | Epicel Cultured epidermal autografts (Genzyme, 2019; Schlatter, 2019) | Vericel, Corp. (United States) | Deep dermal or full thickness burns | US FDA 2007 October | 50 cm2 sheets with a thickness of 2–8 cell layers | Sheet | Cultured keratinocytes on murine 3T3 fibroblasts (each graft is attached to petrolatum gauze backing with titanium surgical clips) | AT | $6,000 to $10,000 per 1% TBSA |
| 5 | Gintuit ACKFBC (Food and Drug Administration, 2019o) | Organogenesis, Inc. (United States) | Surgically created vascular wound bed in the treatment of mucogingival conditions | US FDA 2012 March | Sheets with a diameter and thickness of 75 and 0.75 mm, respectively, which consist of ∼4 million cells | Sheet | Cultured neonatal keratinocytes and fibroblasts on bovine collagen | AL | NA |
| 6 | Omnigraft Dermal Regeneration Matrix (Food and Drug Administration, 2019p; Integra, 2019) | Integra LifeSciences, Corp. (United States) | DFU | US FDA 2016 January | Sheets with two sizes of 4 × 4 and 7 × 7 cm2 | Sheet | Bi-layered bioengineered scaffold, including an inner layer of bovine collagen and chondroitin, and an outer layer consisting of thin silicone | Xn | $499.00 per Kit |
| 7 | MACI (Bloomberg Businessweek, 2018; Food and Drug Administration, 2019q) | Vericel, Corp. (United States) | Single or multiple symptomatic full-thickness cartilage defects of the knee with or without bone involvement in adults | US FDA 2016 December | 3 × 5 cm2 sheets, consist of 500,000 cells per cm2 | Sheet | Cultured chondrocytes on a porcine type I/III collagen membrane | AT | $40,000 per each scaffold |
| EMA 2013 June | |||||||||
| 8 | Holoclar (EMC Inc., 2020; European Medicines Agency, 2020c) | Chiesi Farmaceutici S.p.A (Italy) | Severe limbal stem cell deficiency | EMA 2015 February | 79,000–316,000 cells/cm2 | Sheet | HCEpC containing stem cells | AT | ∼ $102,977 per treatment per eye |
| 9 | Spherox (European Medicines Agency, 2020d; Startseite., 2020) | CO.DON AG (Germany) | Symptomatic articular cartilage defects of the femoral condyle and the patella of the knee with defect sizes up to 10 cm2 in adults | EMA 2017 July | 10–70 spheroids/cm2 | Tube | Tissue spheroids of human matrix-associated chondrocytes | AT | ∼ $12224 per treatment |
| 10 | Holoderm (Kim, 2014; Food and Drug Administration, 2019i; Tego Science, 2019e) | Tego Science (South Korea) | Deep 2nd and 3rd degree burns | South Korea MFDS 2002 December | 56 cm2/piece consisting of 1–4 billion keratinocytes | Sheet | Cultured keratinocyte sheet | AT | $697.76 per each cm2 |
| 11 | Kaloderm (Jae-hyeon, 2018; Global Sources, 2019) | Tego Science (South Korea) | Deep 2nd degree burns and DFU | South Korea MFDS 2005 March (for burns) 2010 January (for DFU) | Each sheet contains > 2 × 107 cells backed by vaseline gauze. The amount is determined considering the size and condition of the wound. | Sheet | Cultured keratinocytes sheet | AL | $26.5 per 1 cm2 for products with 56 cm2 units |
| 12 | CardioCel Pure collagen scaffold (Taylor and Francis Group, 2015; Anteris Technologies Limited, 2019) | Admedus (Singapore) | ASD and VSD | Australia HAS 2014 November | Sheets with three sizes of 4 × 4, 5 × 8, and 14 × 7 cm2 | Sheet | Tissue engineered bovine pericardium | Xn | $421.13 per sheet |
| 13 | JACE Epidermis-derived cell sheet (Drew, 2015; Pharmaceuticals and Medical Devices Agency, 2019) | J-TEC (Japan) | Scars, vitiligo, nevi (birthmarks), ulcers, skin-graft donor sites, severe burns: DDB + DB ≥ 30% | Japan PMDA 2007 October | A sheet consists of 1 × 104 cells/cm2 | Sheet | Keratinocytes sheet cultured on 3T3-J2 cells | AT | S$3,140 per 8 × 10 inch sheet |
| 14 | JACC AT Chondrocyte (Japan Tissue Engineering Co Ltd., 2020) | J-TEC (Japan) | Cartilage defect area >2–4 cm with no alternative therapy | Japan PMDA 2012 July | The quantity of mixture determined by the size of the cartilage defect: defect area x 0.3 ml (final cell density = 2 × 106 cells/mL, 1.33% collagen) | Pre- field syringe | Cultured chondrocytes in atelocollagen gel | AT | $21,300 per knee |
| 15 | HeartSheet SDCS (Pharmaceuticals and Medical Devices Agency, 2019; Pricing of Approved Cell Therapy, 2019) | Terumo, Corp. (Japan) | Severe heart failure due to ischemic heart disease | Japan PMDA 2015 September | 5 skeletal myoblast-derived cell sheets (containing 3 × 108 cells) | Sheet | Skeletal myoblast sheet | AT | A kit: $56000 B kit: $15000 (Each treatment 1 A kit and 5 B kits) |
| 16 | Artificial transfected pigskin (Cheng et al., 2016) | Chongqing Zongshen Junhui Biotechnology (China) | Burns and other traumatic wounds | China CFDA 2007 | NA | Sheet | Bama miniature pig fresh skin tissue transfected with CTLA4Ig gene | Xn | NA |
| 17 | Bilayer artificial skin (Cheng et al., 2016) | Shaanxi Eyre skin Biological Engineering (China) | Deep 2nd degree burn wound, not more than 3rd degree burn wound 20 cm2 (diameter <5 cm) | China CFDA 2007 | NA | Sheet | A bilayer artificial skin with the epidermal layer composed of human epidermal cells and the dermal fibroblasts from human and bovine collagen | AL | NA |
| 18 | Amniosin (SinaCell Enterprise Knowledge Management, 2019) | SinaCell (Iran) | Corneal ulcer, full-thickness DFU > 6 weeks extended through the dermis without tendon, muscle, joint capsule, or bone exposure | Iran FDA 2017 March | One piece of 2 × 2 cm2 implanted | Sheet | Acellular human amniotic membrane-derived dressing | AL | NA |
| 19 | Cell-Amniosin (SinaCell Enterprise Knowledge Management, 2019) | SinaCell (Iran) | Full-thickness DFU > 6 weeks extended through the dermis without tendon, muscle, joint capsule, or bone exposure | Iran FDA 2017 March | One piece of 2 × 2, 3 × 3, 5 × 5, 5 × 10, or 10 × 10 cm2 implanted weekly until the ulcer is healed | Sheet | Cellular human amniotic membrane-derived dressing | AL | NA |
| 20 | Amniodisk (SinaCell Enterprise Knowledge Management, 2019) | SinaCell (Iran) | Corneal ulcer, conjunctival and epithelial damage | Iran FDA 2020 September | One piece of 15 mm circular shape sheet | Sheet | Dehydrated human amniotic membrane-derived ocular allograft | AL | NA |
ACKFBC, allogeneic cultured keratinocytes and fibroblasts in bovine collagen; AL, allogeneic; ASD, atrial septal defect; AT, autologous; CFDA, China Food and Drug Administration; CTLA4Ig, cytotoxic T-lymphocyte associated protein 4 immunoglobulin; DDB, deep dermal burn; DB, dermal burn; DFU, diabetic foot ulcer; EMA, European Medicines Agency; FDA, Food and Drug Administration; HAS, Heath Administration of Singapore; HDFn, human dermal fibroblasts (neonatal); HEKn, human epidermal keratinocytes (neonatal); MFDS, Ministry of Food and Drug Safety; NA, not available; PMDA, Pharmaceuticals and Medical Devices Agency; PRP, platelet-rich plasma; SDCS, skeletal myoblast-derived cell sheet; TBSA, total body surface area; VLU, venous leg ulcer; VSD, ventricular septal defect; Xn, xenogeneic. All prices are in USD.