Bioprinted skin substitutes: advancing regenerative medicine with next-generation tissue engineering

The demand for effective solutions to treat full-thickness skin defects has significantly increased in recent years. Traditional methods, such as autologous split-thickness skin grafts (STSG), remain the gold standard in reconstructive surgery, offering life-saving interventions and functional restoration after trauma or burns. However, these approaches present persistent challenges, including donor site morbidity, scarring, and the necessity of general anesthesia. The advent of high-resolution 3D bioprinting technologies now enables the fabrication of personalized skin substitutes, marking a pivotal evolution in clinical practice and patient care within regenerative medicine.

The challenge of skin reconstruction in modern medicine

Loss of skin due to trauma, severe burns, oncological resection, or chronic ulcers presents complex therapeutic dilemmas. Surgeons must balance rapid wound closure with minimization of both functional and aesthetic sequelae. Conventional surgical approaches require harvesting healthy skin from patients, resulting in secondary wounds, protracted healing at donor sites, pain, contractures, and permanent scarring. In extensive injuries or when donor surfaces are insufficient, therapeutic options become critically limited.

Skin tissue engineering and cell-based therapies have emerged to address these limitations. Initial breakthroughs involved culturing autologous keratinocytes to generate epidermal sheets in vitro, yet these constructs lacked the layered architecture and mechanical stability characteristic of native human skin. The integration of bioprinting platforms has transformed this scenario by allowing precise spatial organization of multiple cell types and biomaterials, more closely replicating physiological skin structure and function.

Technological foundations of next-generation bioprinting platforms

Modern laser-assisted bioprinting (LAB) offers resolution at the cellular and even picoliter scale, ensuring exact placement of keratinocytes, fibroblasts, and extracellular matrix analogues within printed constructs. These systems, designed to comply with GMP standards, enable reproducible manufacturing of clinical-grade bioengineered tissues. Such rigor is essential for medical translation and regulatory acceptance.

A fundamental objective is maintaining high cell viability and construct homogeneity throughout fabrication. Comprehensive traceability, process validation, and histological controls ensure batch-to-batch consistency prior to clinical use. These quality measures are critical to maximize engraftment potential and long-term integration following transplantation.

High-fidelity deposition of multiple cell types in controlled architectures
Maximized viability through non-contact, gentle printing processes
Use of extracellular matrix analogues supporting vascularization and tissue maturation
Strict compliance with European and international GMP guidelines

Poietis’ development of Poieskin: a paradigm shift in dermo-epidermal substitutes

Poietis has pioneered innovation in bioengineered dermo-epidermal skin substitutes through the development of Poieskin. This advanced product results from close collaboration with major academic and clinical institutions, notably the AP-HM (Assistance Publique–Hôpitaux de Marseille). Extensive preclinical evaluation has validated its design, which faithfully reproduces both epidermal and dermal compartments, aiming for permanent and functional wound coverage.

Preclinical studies, conducted in partnership with university hospital teams, established robust methodologies for assessing Poieskin’s efficacy. Large-area transplants in animal models with acute full-thickness wounds enabled direct comparison with human STSG. Key performance indicators included graft take-rate, integration, neovascularization, and inflammatory response—parameters essential for clinical translation.

Manufacturing reliability and tissue performance

Ensuring uniform distribution of cells and matrices within each printed construct is crucial for clinical application. Quality control protocols, based on comprehensive histological analysis, confirmed the reproducibility and architectural integrity of every Poieskin batch. These bioprinted skin grafts demonstrate consistent surface structure and biomechanical properties necessary for successful engraftment in vivo.

In vivo assessments have shown that Poieskin achieves rates of engraftment and blood vessel formation comparable to conventional STSG. Objective imaging modalities, such as laser Doppler and PET scans, quantified tissue perfusion and inflammation longitudinally. Notably, no significant differences were observed between bioprinted constructs and patient-derived grafts, underscoring the therapeutic equivalence of engineered tissues.

Clinical prospects and first-in-human transitions

With GMP-compliant manufacturing workflows established, preparations are underway for clinical trials evaluating the safety and effectiveness of Poieskin in patients. The installation of bioprinting platforms in reference hospitals demonstrates the feasibility of integrating these systems into daily clinical routines. This advancement supports access to personalized skin regeneration, adapting graft geometry and composition to individual defect profiles.

Broad adoption of these technologies is poised to transform burn care, plastic surgery, and dermatology. Treatments will become accessible where traditional options are limited by donor shortages or comorbidities. As more centers acquire next-generation printers, multidisciplinary teams can leverage digital planning to deliver standardized, reproducible, and patient-specific tissue-engineered products on demand.

Broader implications of bioprinted skin for regenerative medicine

The convergence of scientific, industrial, and clinical expertise accelerates the transition of experimental bioengineered tissues to approved therapeutic applications. Active involvement of surgeons, cell therapists, and bioengineers ensures new products meet stringent healthcare requirements and real-world expectations.

Ongoing research aims to incorporate additional cell types—such as melanocytes for pigmentation or immune cells to enhance integration—into future iterations of bioprinted skin. The modularity of custom 3D bioprinting allows adaptation of layer composition, geometry, and vascularization to specific clinical scenarios, facilitating repair of diverse and physiologically demanding skin losses.

Reduction of secondary wound burden and donor site complications
On-demand customization matching anatomical location and defect size
Potential for both temporary dressings and definitive, permanent repairs
New avenues for recreating functional appendages and specialized skin structures

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