3D bioprinting for auricular reconstruction: A review and future perspectives

Congenital abnormalities or acquired trauma to the auricle can result in a need for ear reconstruction and negatively impact a person’s quality of life. Autografting, alloplastic implants, and prostheses are available to treat these issues, but each requires multiple surgical stages and has limitations and complications. Three-dimensional (3D) bioprinting promises to allow the creation of living, patient-specific ear substitutes that could reduce operative morbidity. In this review, we evaluate the current state of 3D bioprinting methods through a systematic search and review of 27 studies, aiming to examine this emerging technology within the context of existing reconstructive options. The included studies were all non-randomized experimental studies, except for a single pilot clinical trial. Most of these studies involved both in vitro and in vivo experiments demonstrating the potential of 3D bioprinting to create functional and anatomically accurate engineered cartilaginous frameworks for surgical implantation. Various ways of optimizing printing were identified, from choosing the most suitable material and cell type for the construct to addressing scaffold deformation and shrinkage issues. 3D printing has the potential to revolutionize reconstructive ear surgery by creating functional and aesthetically pleasing auricles. While more research into printing parameters, bioinks, cell types, and materials could optimize results, the next step is to conduct long-term in vivo clinical trials in humans

Stereolithography

The stereolithography (SLA) process and its methods are introduced in this chapter. After establishing SLA as pertaining to the high-resolution but also high-cost spectrum of the 3D printing technologies, different classifications of SLA processes are presented. Laser-based SLA and digital light processing (DLP), as well as their specialized techniques such as two-photon polymerization (TPP) or continuous liquid interface production (CLIP) are discussed and analyzed for their advantages and shortcomings. Prerequisites of SLA resins and the most common resin compositions are discussed. Furthermore, printable materials and their applications are briefly reviewed, and insight into commercially available SLA systems is given. Finally, an outlook highlighting challenges within the SLA process and propositions to resolve these are offered

Optimal Strategies for Addressing Developmental Breast Asymmetry and the Significance of Symmetrical Treatment: A Systematic Review

BACKGROUND: Approximately one quarter of women are affected by asymmetry as a result of abnormal breast development, which can lead to significant emotional distress. Despite this, there is currently no widely accepted approach for managing this prevalent condition. This systematic review aims to review the available literature on the management of developmental breast asymmetry. METHODS: A comprehensive search in MEDLINE, EMBASE and CENTRAL databases was conducted for primary clinical studies reporting on the management of developmental breast asymmetry from 1962 to November 2022. The primary outcome measures were long term aesthetic outcome and patient reported outcomes. RESULTS: 11 case series and 2 cohort studies were included, comprising a total of 1237 patients with a mean age of 26.5 years (range 14-65). Twelve studies (92%) addressed asymmetry through surgical means, using various augmentation and reduction procedures, while one study (8%) utilised external prosthesis. Meta-analysis of the data was not deemed to be possible due to heterogeneity of data, a narrative synthesis of the literature was provided. CONCLUSIONS: There is no consensus on how to manage developmental breast asymmetry. Furthermore, there is a lack of consistency in the classification of patients with developmental breast asymmetry and in the reporting of outcomes, highlighting the need for a consensus. Further research outlining long term aesthetic and patient reported outcomes is needed to understand which procedures provide optimal outcomes. Additionally, external breast prosthesis is a promising non-surgical alternative and further studies into its efficacy are needed

Biofabrication of the osteochondral unit and its applications: Current and future directions for 3D bioprinting

Multiple prevalent diseases, such as osteoarthritis (OA), for which there is no cure or full understanding, affect the osteochondral unit; a complex interface tissue whose architecture, mechanical nature and physiological characteristics are still yet to be successfully reproduced in vitro. Although there have been multiple tissue engineering-based approaches to recapitulate the three dimensional (3D) structural complexity of the osteochondral unit, there are various aspects that still need to be improved. This review presents the different pre-requisites necessary to develop a human osteochondral unit construct and focuses on 3D bioprinting as a promising manufacturing technique. Examples of 3D bioprinted osteochondral tissues are reviewed, focusing on the most used bioinks, chosen cell types and growth factors. Further information regarding the applications of these 3D bioprinted tissues in the fields of disease modelling, drug testing and implantation is presented. Finally, special attention is given to the limitations that currently hold back these 3D bioprinted tissues from being used as models to investigate diseases such as OA. Information regarding improvements needed in bioink development, bioreactor use, vascularisation and inclusion of additional tissues to further complete an OA disease model, are presented. Overall, this review gives an overview of the evolution in 3D bioprinting of the osteochondral unit and its applications, as well as further illustrating limitations and improvements that could be performed explicitly for disease modelling

Evaluation of a synthetic peptide-based bioink (PeptiInk Alpha 1) for in vitro 3D bioprinting of cartilage tissue models

Cartilage pathology in human disease is poorly understood and requires further research. Various attempts have been made to study cartilage pathologies using in vitro human cartilage models as an alternative for preclinical research. Three-dimensional (3D) bioprinting is a technique that has been used to 3D-bioprint cartilage tissue models in vitro using animal-derived materials such as gelatine or hyaluronan, which present challenges in terms of scalability, reproducibility, and ethical concerns. We present an assessment of synthetic self-assembling peptides as bioinks for bioprinted human in vitro cartilage models. Primary human chondrocytes were mixed with PeptiInk Alpha 1, 3D-bioprinted and cultured for 14 days, and compared with 3D chondrocyte pellet controls. Cell viability was assessed through LIVE/DEAD assays and DNA quantification. High cell viability was observed in the PeptiInk culture, while a fast decrease in DNA levels was observed in the 3D pellet control. Histological evaluation using hematoxylin and eosin staining and immunofluorescence labeling for SOX-9, collagen type II, and aggrecan showed a homogeneous cell distribution in the 3D-bioprinted PeptiInks as well as high expression of chondrogenic markers in both control and PeptiInk cultures. mRNA expression levels assessed by - qRT-PCR (quantitative real time-polymerase chain reaction) confirmed chondrogenic cell behavior. These data showed promise in the potential use of PeptiInk Alpha 1 as a bioprintable manufacturing material for human cartilage in vitro models

Current standards and ethical landscape of engineered tissues—3D bioprinting perspective

Tissue engineering is an evolving multi-disciplinary field with cutting-edge technologies and innovative scientific perceptions that promise functional regeneration of damaged tissues/organs. Tissue engineered medical products (TEMPs) are biomaterial-cell products or a cell-drug combination which is injected, implanted or topically applied in the course of a therapeutic or diagnostic procedure. Current tissue engineering strategies aim at 3D printing/bioprinting that uses cells and polymers to construct living tissues/organs in a layer-by-layer fashion with high 3D precision. However, unlike conventional drugs or therapeutics, TEMPs and 3D bioprinted tissues are novel therapeutics and need different regulatory protocols for clinical trials and commercialization processes. Therefore, it is essential to understand the complexity of raw materials, cellular components, and manufacturing procedures to establish standards that can help to translate these products from bench to bedside. These complexities are reflected in the regulations and standards that are globally in practice to prevent any compromise or undue risks to patients. This review comprehensively describes the current legislations, standards for TEMPs with a special emphasis on 3D bioprinted tissues. Based on these overviews, challenges in the clinical translation of TEMPs & 3D bioprinted tissues/organs along with their ethical concerns and future perspectives are discussed

Neck Collar Assessment for People Living With Motor Neuron Disease: Are Current Outcome Measures Suitable?

A majority of people living with motor neuron disease (MND) experience weakness of the neck and as a result, experience head drop. This exacerbates problems with everyday activities (eating, talking, breathing, etc). Neck collars are often used to support head drop; however, these are typically designed for prehospitalization settings to manage and brace the cervical region of the spine. As a result, it has been recorded that people living with MND often reject these collars for a variety of reasons but most notably because they are too restricting. The current standardized outcome measures (most notably restricting cervical range of motion) used for neck collars are summarized herein along with whether they are suitable for a bespoke neck collar specifically designed for people living with MND

Accuracy of 3D printed spine models for pre-surgical planning of complex adolescent idiopathic scoliosis (AIS) in spinal surgeries: a case series

Adolescent idiopathic scoliosis (AIS) is a noticeable spinal deformity in both adult and adolescent population. In majority of the cases, the gold standard of treatment is surgical intervention. Technological advancements in medical imaging and 3D printing have revolutionised the surgical planning and intraoperative decision making for surgeons in spinal surgery. However, its applicability for planning complex spinal surgeries is poorly documented with human subjects. The objective of this study is to evaluate the accuracy of 3D printed models for complex spinal deformities based on Cobb angles between 40° to 95°.This is a retrospective cohort study where, five CT scans of the patients with AIS were segmented and 3D printed for evaluating the accuracy. Consideration was given to the Inter-patient and acquisition apparatus variability of the CT-scan dataset to understand the effect on trueness and accuracy of the developed CAD models. The developed anatomical models were re-scanned for analysing quantitative surface deviation to assess the accuracy of 3D printed spinal models. Results show that the average of the root mean square error (RMSE) between the 3DP models and virtual models developed using CT scan of mean surface deviations for the five 3d printed models was found to be 0.5§0.07 mm. Based on the RMSE, it can be concluded that 3D printing based workflow is accurate enough to be used for presurgical planning for complex adolescent spinal deformities. Image acquisition and post processing parameters, type of 3D printing technology plays key role in acquiring required accuracy for surgical applications

Ceramic Materials for 3D Printing of Biomimetic Bone Scaffolds – Current state–of–the–art & Future Perspectives

Ceramic bone implants have potential properties ideal for long-term implantation applications. On comparison with other materials, ceramic biomaterials have advantages such as biocompatibility, low cost, osteoconductivity, osteoinductivity, corrosion resistance, and can be made into various shapes with desired surface properties. Among transplantation surgeries, bone transplantation is the second largest in the globe after blood transfusion which is an indication for rising hope on the potential treatment options for bone. 3D printing is one of the most advanced fabrication techniques to create customized bone implants using materials such as ceramics and their composites. Developing bone scaffolds that precisely recapitulate the mechanical properties and other biological functions of bone remains a major challenge. However, extensive research on ceramic biomaterials have resulted in the successful 3D printing of complex bony designs with >50% porosity with cortical bone mechanical properties. This review critically analyses the use of various 3D printing techniques to fabricate ceramic bone scaffolds. Further, various natural and synthetic ceramic materials for producing customized ceramic implants are discussed along with potential clinical applications. Finally, a list of companies that offer customized 3D printed implants and the future on clinical translation of 3D printed ceramic bone implants are outlined

Mesenchymal stromal cells and platelet-rich plasma promote tendon allograft healing in ovine anterior cruciate ligament reconstruction

Purpose The effect of bone marrow mesenchymal stromal cells (BMSCs) and platelet-rich plasma (PRP) on tendon allograft maturation in a large animal anterior cruciate ligament (ACL) reconstruction model was reported for the first time. It was hypothesised that compared with non-augmented ACL reconstruction, BMSCs and PRP would enhance graft maturation after 12 weeks and this would be detected using magnetic resonance imaging (MRI). Methods Fifteen sheep underwent unilateral tendon allograft ACL reconstruction using aperture fixation and were randomised into three groups (n = 5). Group 1 received 10 million allogeneic BMSCs in 2 ml fibrin sealant; Group 2 received 12 ml PRP in a plasma clot injected into the graft and bone tunnels; and Group 3 (control) received no adjunctive treatment. At autopsy at 12 weeks, a graft maturation score was determined by the sum for graft integrity, synovial coverage and vascularisation, graft thickness and apparent tension, and synovial sealing at tunnel apertures. MRI analysis (n = 2 animals per group) of the signal–noise quotient (SNQ) and fibrous interzone (FIZ) was used to evaluate intra-articular graft maturation and tendon–bone healing, respectively. Spearman’s rank correlation coefficient (r) of SNQ, autopsy graft maturation score and bone tunnel diameter were analysed. Results The BMSC group (p = 0.01) and PRP group (p = 0.03) had a significantly higher graft maturation score compared with the control group. The BMSC group scored significantly higher for synovial sealing at tunnel apertures (p = 0.03) compared with the control group. The graft maturation score at autopsy significantly correlated with the SNQ (r = − 0.83, p < 0.01). The tunnel diameter of the femoral tunnel at the aperture (r = 0.883, p = 0.03) and mid-portion (r = 0.941, p = 0.02) positively correlated with the SNQ. Conclusions BMSCs and PRP significantly enhanced graft maturation, which indicates that orthobiologics can accelerate the biologic events in tendon allograft incorporation. Femoral tunnel expansion significantly correlated with inferior maturation of the intra-articular graft. The clinical relevance of this study is that BMSCs and PRP enhance allograft healing in a translational model, and biological modulation of graft healing can be evaluated non-invasively using MRI