3D bioprinting for stickler syndrome: a transformative approach to early-onset joint degeneration

To the Editor,

Stickler syndrome or hereditary progressive arthro-ophthalmopathy is a rare inherited connective tissue disorder caused by mutations in collagen genes affecting approximately 1 in 7500 individuals. It is characterized by ocular, skeletal, orofacial, and auditory abnormalities, often leading to severe cartilage degradation and early onset osteoarthritis[1]. A typifying feature of this syndrome is early onset degenerative joint disease, with around 75% of patients developing osteoarthritis, particularly in weight-bearing joints, before the age of 30 years[2]. Such patients suffer debilitating joint pains and their quality of life is significantly affected by the disease. Current treatment options offer only symptomatic support and treatments such as joint replacement, are suboptimal for younger patients due to limited durability and poor integration with native tissues, which demands an urgent need for novel interventions[2]. This article is in line with the TITAN Guidelines on the need for transparency in AI use in healthcare[3].

Recent advancements in 3D bio printing offers a new paradigm for disease-modifying treatment of Stickler syndrome patients. Bioprinting is a novel, advanced 3D tissue engineering technique that precisely uses bio-inks composed of biomaterials and living cells to fabricate complex, functional tissue constructs such as organs and tissues with high precision. Although still developing, this technology is anticipated to show encouraging outcomes with applications in producing transplantable skin, cartilage, and bone[4]. 3D bio printing holds significant promise for creating personalized cartilage implants, offering new hope for patients with cartilage disorders like Stickler syndrome.

Recent studies have demonstrated the potential use of 3D bioprinted joints for joint repair in Stickler syndrome. A systematic review was conducted that analyzed 27 studies for articular cartilage bioprinting, which illustrated the ability of this technology to recapitulate the complex zonal microarchitecture of native hyaline cartilage on account of its unique abilities, varied techniques, and in situ bioprinting, allowing replication of anatomical structures, biological function, and mechanical properties of native articular cartilage. This review demonstrated great capacity for cartilage reconstruction and future in vivo implantation, which can have great prospects in the future for the definitive treatment of patients with Stickler’s syndrome if adequate resources and attention are given to this novel technique and further large-scale trials take this into account[5]. Another comprehensive review also focused on the importance of stem cells with hydrogels and bioinks in the fabrication of living, organized tissue constructs via layer-by-layer deposition, thus allowing the control of cell distribution and mechanical and chemical properties[6].

Despite its promising potential for successful cartilage reconstruction and future in vivo implantation, and possessing a strong potential for the definitive treatment for Stickler’s syndrome patients, several challenges remain, including difficulties in achieving high-precision cell placement, uniform cell distribution, mechanical strength and durability, and innervation and vascularization. However, 3D bioprinting through precise, layer-by-layer fabrication of scaffolds closely mimics the complex architecture of native cartilage, including its zonal organization and mechanical properties, and can produce impressive outcomes if scaled for clinical translation, particularly in repairing osteochondral defects prevalent in genetic connective tissue disorders like Stickler’s syndrome. Nevertheless, current studies are mostly preclinical, and long-term effectiveness and safety in humans remain unclear[4]. Further research and large-scale clinical trials are needed before these solutions, which are anticipated to bring a revolution in the treatment of degenerative joint disease in Stickler syndrome patients, can become widely available.

Stickler syndrome is a significant clinical challenge due to limited therapeutic options especially in patients with early onset osteoarthritis. The technological advent of 3D bio printing however has opened up new avenues in regenerative medicine. Despite its present limitations and the need for further clinical validation, the ability of this technology to replicate complex cartilage architecture which can mimic the function of native tissues suggests a prospective outlook for joint repair in patients with hereditary connective tissue disorders such as Stickler syndrome patients with early onset osteoarthritis. Continued investment in research and translational efforts is vital in bringing this innovative approach into effective long-term use for the plight of patients who have Stickler syndrome.

Ethical approval

This article does not involve any studies with human participants or animals performed by any of the authors; therefore, ethical approval was not required.

Consent

Not applicable. This article does not include any studies involving human participants or identifiable individual data.

Sources of funding

None.

Author contributions

S.A.: conceptualization; writing – original draft; M.N.: conceptualization; writing – original draft; M.T.: writing – original draft; writing – review & editing; S.B.I.: writing – review & editing; L.S.: writing – review & editing.

Conflicts of interest disclosure

None.

Guarantor

Laiba Shamim.

Research registration unique identifying number (UIN)

Not applicable.

Peer and provenance statement

None.

Data availability statement

Not applicable.