The combined application of stem cells and three-dimensional bioprinting scaffolds for the repair of spinal cord injury

Spinal cord injury is considered one of the most difficult injuries to repair and has one of the worst prognoses for injuries to the nervous system.Following surgery,the poor regenerative capacity of nerve cells and the generation of new scars can make it very difficult for the impaired nervous system to restore its neural functionality.Traditional treatments can only alleviate secondary injuries but cannot fundamentally repair the spinal cord.Consequently,there is a critical need to develop new treatments to promote functional repair after spinal cord injury.Over recent years,there have been seve ral developments in the use of stem cell therapy for the treatment of spinal cord injury.Alongside significant developments in the field of tissue engineering,three-dimensional bioprinting technology has become a hot research topic due to its ability to accurately print complex structures.This led to the loading of three-dimensional bioprinting scaffolds which provided precise cell localization.These three-dimensional bioprinting scaffolds co uld repair damaged neural circuits and had the potential to repair the damaged spinal cord.In this review,we discuss the mechanisms underlying simple stem cell therapy,the application of different types of stem cells for the treatment of spinal cord injury,and the different manufa cturing methods for three-dimensional bioprinting scaffolds.In particular,we focus on the development of three-dimensional bioprinting scaffolds for the treatment of spinal cord injury.

Preparation of Dashanzha Wan by three-dimensional printing

Objective:To use three-dimensional(3D)printing technology to prepare Dashanzha Wan.Methods:The standard formula proportion of Dashanzha Wan was used to prepare printable materials(normally called the ink)for 3D printing,and different doses and shapes of Dashanzha Wan were prepared.Then,the rheological properties,texture characteristics,scanning electron microscopy,and content of ursolic acid were evaluated.Results:Dashanzha Wan ink showed good shear thinning properties,which is very suitable for 3D printing.The printed sample had a beautiful and regular shape with high resolution.Meanwhile,ursolic acid content in 3D-printed Dashanzha Wan aligned with the ursolic acid content shown in the Pharmacopoeia of the People's Republic of China 2020.Conclusion:The 3D-printed Dashanzha Wan has a better texture,and can be shaped into various shapes according to individual needs,which would increase patients’interest when taking medicine.Moreover,3D printing of Dashanzha Wan could be easily integrated into the digital life system,enabling online customization or use at home.This study reveals that 3D printing technology is a promising method for the production of traditional Chinese medicine with personalized appearance,dosage,and texture,which is suitable for a broader population.

Recent advances in meniscus-on-demand three-dimensional micro-and nano-printing for electronics and photonics

The continual demand for modern optoelectronics with a high integration degree and customized functions has increased requirements for nanofabrication methods with high resolution,freeform,and mask-free.Meniscus-on-demand three-dimensional(3D)printing is a high-resolution additive manufacturing technique that exploits the ink meniscus formed on a printer nozzle and is suitable for the fabrication of micro/nanoscale 3D architectures.This method can be used for solution-processed 3D patterning of materials at a resolution of up to100 nm,which provides an excellent platform for fundamental scientific studies and various practical applications.This review presents recent advances in meniscus-on-demand 3D printing,together with historical perspectives and theoretical background on meniscus formation and stability.Moreover,this review highlights the capabilities of meniscus-on-demand 3D printing in terms of printable materials and potential areas of application,such as electronics and photonics.

A New Three-Dimensional(3D)Printing Prepress Algorithm for Simulation of Planned Surgery for Congenital Heart Disease

Background:Three-dimensional printing technology may become a key factor in transforming clinical practice and in significant improvement of treatment outcomes.The introduction of this technique into pediatric cardiac surgery will allow us to study features of the anatomy and spatial relations of a defect and to simulate the optimal surgical repair on a printed model in every individual case.Methods:We performed the prospective cohort study which included 29 children with congenital heart defects.The hearts and the great vessels were modeled and printed out.Measurements of the same cardiac areas were taken in the same planes and points at multislice computed tomography images(group 1)and on printed 3D models of the hearts(group 2).Pre-printing treatment of the multislice computed tomography data and 3D model preparation were performed according to a newly developed algorithm.Results:The measurements taken on the 3D-printed cardiac models and the tomographic images did not differ significantly,which allowed us to conclude that the models were highly accurate and informative.The new algorithm greatly simplifies and speeds up the preparation of a 3D model for printing,while maintaining high accuracy and level of detail.Conclusions:The 3D-printed models provide an accurate preoperative assessment of the anatomy of a defect in each case.The new algorithm has several important advantages over other available programs.They enable the development of customized preliminary plans for surgical repair of each specific complex congenital heart disease,predict possible issues,determine the optimal surgical tactics,and significantly improve surgical outcomes.

Role of three-dimensional printing and artificial intelligence in the management of hepatocellular carcinoma:Challenges and opportunities

Hepatocellular carcinoma(HCC)constitutes the fifth most frequent malignancy worldwide and the third most frequent cause of cancer-related deaths.Currently,treatment selection is based on the stage of the disease.Emerging fields such as three-dimensional(3D)printing,3D bioprinting,artificial intelligence(AI),and machine learning(ML)could lead to evidence-based,individualized management of HCC.In this review,we comprehensively report the current applications of 3D printing,3D bioprinting,and AI/ML-based models in HCC management;we outline the significant challenges to the broad use of these novel technologies in the clinical setting with the goal of identifying means to overcome them,and finally,we discuss the opportunities that arise from these applications.Notably,regarding 3D printing and bioprinting-related challenges,we elaborate on cost and cost-effectiveness,cell sourcing,cell viability,safety,accessibility,regulation,and legal and ethical concerns.Similarly,regarding AI/ML-related challenges,we elaborate on intellectual property,liability,intrinsic biases,data protection,cybersecurity,ethical challenges,and transparency.Our findings show that AI and 3D printing applications in HCC management and healthcare,in general,are steadily expanding;thus,these technologies will be integrated into the clinical setting sooner or later.Therefore,we believe that physicians need to become familiar with these technologies and prepare to engage with them constructively.

Three-dimensional(3D) Printing Technology Assisted by Minimally Invasive Surgery for Pubic Rami Fractures

The feasibility of three-dimensional (3D) printing technology cgmbined with minimally invasive surgery in the treatment of pubic rami fractures was explored.From August 2015 to October 2017,a series of 30 patients who underwent surgical stabilization of their anterior pelvic ring (all utilizing the 3D printing technology)by one surgeon at a single hospital were studied.The minimally invasive incisions were made through anterior inferior cilia spine and pubic nodule.Data collected included the operative duration,the blood loss,the damage of the important tissue,the biographic union and therecovery of the function after the operation.Measurements on inlet and outlet pelvic cardiograph were made immediately post-operation and at all follow-up clinic visits.The scores of reduction and function were measured during follow-up.Results showed that the wounds of 30 patients were healed in the first stage,and there was no injury of important structures such as blood vessels and nerves.According to the Matta criteria,excellent effectiveness was obtained in 22 cases and good in 8 cases.According to the functional evaluation criteria of Majeed,excellent effectiveness was obtained in 21 cases and good in 9 cases.It was suggested that the 3D printing technology assisted by minimally invasive surgery can better evaluate the pelvic fracture before operation,which was helpful in plate modeling, and can shorten surgery duration and reduce intraoperative blood loss and complications. The positioning accuracy was improved,and better surgical result was finally achieved.

Use of three-dimensional printing in preoperative planning in orthopaedic trauma surgery: A systematic review and meta-analysis

BACKGROUND With the increasing complexity of surgical interventions performed in orthopaedic trauma surgery and the improving technologies used in threedimensional(3D)printing,there has been an increased interest in the concept.It has been shown that 3D models allow surgeons to better visualise anatomy,aid in planning and performing complex surgery.It is however not clear how best to utilise the technique and whether this results in better outcomes.AIM To evaluate the effect of 3D printing used in pre-operative planning in orthopaedic trauma surgery on clinical outcomes.METHODS We performed a comprehensive systematic review of the literature and a metaanalysis.Medline,Ovid and Embase were searched from inception to February 8,2018.Randomised controlled trials,case-control studies,cohort studies and case series of five patients or more were included across any area of orthopaedic trauma.The primary outcomes were operation time,intra-operative blood loss and fluoroscopy used.RESULTS Seventeen studies(922 patients)met our inclusion criteria and were reviewed.The use of 3D printing across all specialties in orthopaedic trauma surgery demonstrated an overall reduction in operation time of 19.85%[95%confidence intervals(CI):(-22.99,-16.71)],intra-operative blood loss of 25.73%[95%CI:(-31.07,-20.40)],and number of times fluoroscopy was used by 23.80%[95%CI:(-38.49,-9.10)].CONCLUSION Our results suggest that the use of 3D printing in pre-operative planning in orthopaedic trauma reduces operative time,intraoperative blood loss and the number of times fluoroscopy is used.

Application of the Guiding Template Designed by Three-dimensional Printing Data for the Insertion of Sacroiliac Screws:a New Clinical Technique

This study is aimed to explore the clinical application of the guiding template designed by three-dimensional printing data for the insertion of sacroiliac screws.A retrospective study of 7 cases (from July 2016 to December 2016),in which the guiding template printed by the three-dimensional printing technique was used for the insertion of sacroiliac screws of patients with posterior ring injuries of pelvis,was performed.Totally,4 males and 3 females were included in template group,aged from 38to 65years old (mean 50.86±8.90).Of them,5 had sacral fractures (3 with Denis type Ⅰ and 2 with type Ⅱ)and 2 the separation of sacroiliac joint.Guiding templates were firstly made by the three-dimensional printing technique based on the pre-operative CT data. Surgical operations for the stabilization of pelvic ring by applying the guiding templates were carried out.A group of 8 patients with sacroiliac injuries treated by percutaneous sacroiliac screws were analyzed as a control group retrospectively.The time of each screw insertion,volume of intra-operative blood loss,and the exposure to X ray were analyzed and the Matta's radiological criteria were used to evaluate the reduction quality.The Majeed score was used to evaluate postoperative living quality.The visual analogue scale (VAS)was applied at different time points to judge pain relief of coccydynia.All the 7 patients in the template group were closely followed up radiographically and clinically for 14 to 20 months,mean (16.57±2.44)months.Totally 9 sacroiliac screws for the S 1 and S2 vertebra were inserted in the 7 patients.The time length for each screw insertion ranged from 450 to 870 s,mean (690.56±135.68)s,and the number of times of exposure to X ray were 4 to 8,mean (5.78±1.20).The intra-operative blood loss ranged from 45to 120 mL,mean (75±23.32)mL.According to Matta's radiology criteria,the fracture and dislocation reduction were excellent in 6cases and good in 1.The pre-operative VAS score ranged from 5.2 to 8.1,mean (7.13±1.00).The average one-week/six-month post-operative VAS was (5.33±0.78)and (1.33±0.66),respectively (P<0.05 when compared with pre-operative VAS).The 12-month post-operative Majeed score ranged from 86 to 92,mean (90.29±2.21).The three-dimensional printed guiding template for sacroiliac screw insertion,which could significantly shorten the operation time,provide a satisfied outcome of the stabilization of the pelvic ring,and protect doctors and patients from X-ray exposure,might be a practical and valuable new clinical technique.

Three-dimensional printing for heart diseases: clinical application review

Heart diseases remain the top threat to human health,and the treatment of heart diseases changes with each passing day.Convincing evidence shows that three-dimensional(3D)printing allows for a more precise understanding of the complex anatomy associated with various heart diseases.In addition,3D-printed models of cardiac diseases may serve as effective educational tools and for hands-on simulation of surgical interventions.We introduce examples of the clinical applications of different types of 3D printing based on specific cases and clinical application scenarios of 3D printing in treating heart diseases.We also discuss the limitations and clinically unmet needs of 3D printing in this context.

Three-dimensional bio-printing: A new frontier in oncology research

Current research in oncology deploys methods that rely principally on two-dimensional(2D) mono-cell cultures and animal models.Although these methodologies have led to significant advancement in the development of novel experimental therapeutic agents with promising anticancer activity in the laboratory, clinicians still struggle to manage cancer in the clinical setting.The disappointing translational success is attributable mainly to poor representation and recreation of the cancer microenvironment present in human neoplasia.Threedimensional(3D) bio-printed models could help to simulate this micro-environment, with recent bio-printing of live human cells demonstrating that effective in vitro replication is achievable.This literature review outlines up-to-date advancements and developments in the use of 3D bio-printed models currently being used in oncology research.These innovative advancements in 3D bio-printing open up a new frontier for oncology research and could herald an era of progressive clinical cancer therapeutics.

Design and Fabrication of Drug Delivery Devices with Complex Architectures Based on Three-dimensional Printing Technique

A new type of implantable drug delivery devices （ DDD ） with complicated architectures were fubricated by three-dimensional printing technique, employing levofloxacin （LVFX） as a model drug. Processing parameters were optimized in riew of the layer thickness, spucing between printed lines, flow rate of liquid binder and the fast axis speed. The prepared DDD prototype consists of a double-layer structure, of which the upper region is a reservoir system and the lower region is a matrix one. The in vitro release test revealed that LVFX was released in a dual-puse pattern. This DDD may present a new strategy for the prophylaxis and treatment of diseases such as bone infection in the near future.

Magnetic resonance imaging-three-dimensional printing technology fabricates customized scaffolds for brain tissue engineering

Conventional fabrication methods lack the ability to control both macro- and micro-structures of generated scaffolds. Three-dimensional printing is a solid free-form fabrication method that provides novel ways to create customized scaffolds with high precision and accuracy. In this study, an electrically controlled cortical impactor was used to induce randomized brain tissue defects. The overall shape of scaffolds was designed using rat-specific anatomical data obtained from magnetic resonance imaging, and the internal structure was created by computer- aided design. As the result of limitations arising from insufficient resolution of the manufacturing process, we magnified the size of the cavity model prototype five-fold to successfully fabricate customized collagen-chitosan scaffolds using three-dimensional printing. Results demonstrated that scaffolds have three-dimensional porous structures, high porosity, highly specific surface areas, pore connectivity and good internal characteristics. Neural stem cells co-cultured with scaffolds showed good viability, indicating good biocompatibility and biodegradability. This technique may be a promising new strategy for regenerating complex damaged brain tissues, and helps pave the way toward personalized medicine.

A combination of digital design and three-dimensional printing to assist treatment of thoracolumbar compression fractures using percutaneous kyphoplasty

Objective:To evaluate the clinical efficacy of the preoperative digita1 design combined with three dimensional(3D)printing models to assist percutaneous kyphoplasty(PKP)treatment for thoracolumbar compression frac tures.Methods:From January 2018 to August 2020,we obtained data of 99 patients diagnosed thoracolumbar compression fractures.These patients were divided into control group(n=50)underwent traditional PKP surgery,and observation group(n=49)underwent preoperative digital design combined with 3D printing model assisted PKP treatment.The clinical efficacy was evaluated with five parameters,including operation time,number of intraoperative radiographs,visual analogue scale(VAS)score,Cobb Angle change,and high compression rate of injured vertebrae.Results:There were statistically significant differences of operation time and number of intraoperative radio graphs between the two groups(P<0.05).For VAS score,Cobb Angle change and vertebral height compression rate,all of these three parameters were significantly improved when the patients accepted surgery teatment in two groups(P<0.05).However,there were no significant differences between control group and observation group for these three parameters either before or after surgery(P>0.05).Conclusions:Through the design of preoperative surgical guide plate and the application of 3D printing model to guide the operation,the precise design of preoperative surgical puncture site and puncture Angle of the injured vertebra was realized,the number of intraoperative radiographs was reduced,the operation time was shortened and the operation efficiency was improved.

Prenatal diagnosis of isolated lateral facial cleft by ultrasonography and three-dimensional printing:A case report

BACKGROUND Lateral facial clefts are atypical with a low incidence in the facial cleft spectrum.With the development of ultrasonography(US)prenatal screening,such facial malformations can be detected and diagnosed prenatally rather than at birth.Although three-dimensional US(3DUS)can render the fetus'face via 3D reconstruction,the 3D images are displayed on two-dimensional screens without field depth,which impedes the understanding of untrained individuals.In contrast,a 3D-printed model of the fetus'face helps both parents and doctors develop a more comprehensive understanding of the facial malformation by creating more interactive aspects.Herein,we present an isolated lateral facial cleft case that was diagnosed via US combined with a 3D-printed model.CASE SUMMARY A 31-year-old G2P1 patient presented for routine prenatal screening at the 22nd wk of gestation.The coronal nostril-lip section of two-dimensional US(2DUS)demonstrated that the fetus'bilateral oral commissures were asymmetrical,and left oral commissure was abnormally wide.The left oblique-coronal section showed a cleft at the left oral commissure which extended to the left cheek.The results of 3DUS confirmed the cleft.Furthermore,we created a model of the fetal face using 3D printing technology,which clearly presented facial malformations.The fetus was diagnosed with a left lateral facial cleft,which was categorized as a No.7 facial cleft according to the Tessier facial cleft classification.The parents terminated the pregnancy at the 24th wk of gestation after parental counseling.CONCLUSION In the diagnostic course of the current case,in addition to the traditional application of 2D and 3DUS,we created a 3D-printed model of the fetus,which enhanced diagnostic evidence,benefited the education of junior doctors,improved parental counseling,and had the potential to guide surgical planning.

Three-dimensional printing technology for patient-matched instrument in treatment of cubitus varus deformity:A case report

BACKGROUND Recently,medical three-dimensional printing technology(3DPT)has demonstrated potential benefits for the treatment of cubitus varus deformity(CVD)by improving accuracy of the osteotomy through the use of an osteotomy guide,with or without a patient-mated plate.Here,we present an interesting CVD case,involving a patient who was treated with corrective biplanar chevron osteotomy using an innovative customized osteotomy guide and a newly designed patient-matched monoblock crosslink plate created with 3DPT.CASE SUMMARY A 32-year-old female presented with a significant CVD from childhood injury.A computer simulation was processed using images from computerized tomography scans of both upper extremities.The biplanar chevron osteotomy was designed to create identical anatomy between the mirror image of the contralateral distal humerus and the osteotomized distal humerus.Next,the customized osteotomy guide and patient-matched monoblock crosslink plate were designed and printed.A simulation osteotomy was created for the real-sized bone model,and the operation was performed using the posterior paratricipital approach with k-wire positioning from the customized osteotomy guide as a predrilled hole for screw fixation to achieve immediate control of the reduction after osteotomy.Our method allowed for successful treatment of the CVD case,significantly improving the patient’s radiographic and clinical outcomes,with satisfactory result.CONCLUSION 3DPT-created patient-matched osteotomy guide and instrumentation provides accurate control during CVD correction.

Intraoperative application of three-dimensional printed guides in total hip arthroplasty: A systematic review

BACKGROUND Acetabular component positioning in total hip arthroplasty(THA)is of key importance to ensure satisfactory post-operative outcomes and to minimize the risk of complications.The majority of acetabular components are aligned freehand,without the use of navigation methods.Patient specific instruments(PSI)and three-dimensional(3D)printing of THA placement guides are increasingly used in primary THA to ensure optimal positioning.AIM To summarize the literature on 3D printing in THA and how they improve acetabular component alignment.METHODS PubMed was used to identify and access scientific studies reporting on different 3D printing methods used in THA.Eight studies with 236 hips in 228 patients were included.The studies could be divided into two main categories;3D printed models and 3D printed guides.RESULTS 3D printing in THA helped improve preoperative cup size planning and post-operative Harris hip scores between intervention and control groups(P=0.019,P=0.009).Otherwise,outcome measures were heterogeneous and thus difficult to compare.The overarching consensus between the studies is that the use of 3D guidance tools can assist in improving THA cup positioning and reduce the need for revision THA and the associated costs.CONCLUSION The implementation of 3D printing and PSI for primary THA can significantly improve the positioning accuracy of the acetabular cup component and reduce the number of complications caused by malpositioning.

Three-dimensional printing in paediatric orthopaedic surgery

Three-dimensional(3D)printing is a rapidly evolving and promising field to improve outcomes of orthopaedic surgery.The use of patient-specific 3D-printed models is specifically interesting in paediatric orthopaedic surgery,as limb deformity corrections often require an individual 3D treatment.In this editorial,various operative applications of 3D printing in paediatric orthopaedic surgery are discussed.The technical aspects and the imaging acquisition with computed tomography and magnetic resonance imaging are outlined.Next,there is a focus on the intraoperative applications of 3D printing during paediatric orthopaedic surgical procedures.An overview of various upper and lower limb deformities in paediatrics is given,in which 3D printing is already implemented,including posttraumatic forearm corrections and proximal femoral osteotomies.The use of patient-specific instrumentation(PSI)or guiding templates during the surgical procedure shows to be promising in reducing operation time,intraoperative haemorrhage and radiation exposure.Moreover,3D-printed models for the use of PSI or patient-specific navigation templates are promising in improving the accuracy of complex limb deformity surgery in children.Lastly,the future of 3D printing in paediatric orthopaedics extends beyond the intraoperative applications;various other medical applications include 3D casting and prosthetic limb replacement.In conclusion,3D printing opportunities are numerous,and the fast developments are exciting,but more evidence is required to prove its superiority over conventional paediatric orthopaedic surgery.

Application Status and Prospect of Three-Dimensional Printing Technology in the Field of Medical Devices

Three-dimensional(3D)printing technology belongs to a new manufacturing science and has been widely used in various fields of industry.This article will apply 3D printing technology as its main research topic,with emphasis on its application in the field of medical devices and prospects for contribution.

Three-dimensional printing for the accurate orthopedics:clinical cases analysis

As an emerging technology to promote the combination of medicine and industry,the three-dimensional(3D)printing has developed rapidly in the fields of orthopedics,while its unique advantages in improving precise treatment still need to be further popularized.In this report,our team have exhibited several classic cases of integrating 3D printing into orthopedic clinical application,thereby further elaborating thoughts and opinions on the significance of 3D printing in the orthopedic clinical application,technical advantages,existing main problems and coping strategies.

An erratum on “Application of three-dimensional printing in interventional medicine” [J Interv Med(February 2020) 1–16]

After the publication of this work,1 the authors noticed and confirmed that the Funding Information was mistakenly omitted from the article.The statement“This study was supported by grants from the National Natural Science Foundation of China,grant no.81370041,81471760,81671655,the Outstanding Clinical Discipline Project of Shanghai Pudong,grant no.PWYgy2018-04.The authors declare that they have no conflicts of interest.”should be included in the Funding information section of the paper which is missing.We apologize for the error.