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Traumatic and degenerative lesions in the cartilage are one of the most difficult and frustrating types of injuries for orthopedic surgeons and patients. Future developments in medical science, regenerative medicine, and materials science may allow the repair of human body parts using 3D bioprinting techniques and serve as a basis for new therapies for tissue and organ regeneration. One future possibility is the treatment of joint cartilage defects with in vivo 3D printing from biological/biocompatible materials to produce a suitable cell attachment and proliferation environment in the damaged site and employ the natural recovery potential of the body. This study focuses on the perspectives of orthopedic surgeons regarding the key factors/determinants and perceived clinical value of a new therapeutic option.
This study aimed to determine the knowledge and expectations of orthopedic surgeons regarding the clinical use of bioprinted cartilage.
The survey, conducted anonymously and self-managed, was sent to orthopedic surgeons from the Catalan Society of Orthopedic and Traumatology Surgery. In accordance with the method devised by Eysenbach, the Checklist for Reporting Results of Internet E-Surveys was used to analyze the results. The following factors were taken into consideration: the type and origin of the information received; its relevance; the level of acceptance of new technologies; and how the technology is related to age, years, and place of experience in the field.
Of the 86 orthopedic surgeons included, 36 believed the age of the patient was a restriction, 53 believed the size of the lesion should be between 1 and 2 cm to be considered for this type of technology, and 51 believed that the graft should last more than 5 years. Surgeons over 50 years of age (38/86, 44%) gave more importance to clinical evidence as compared to surgeons from the other age groups.
The perspective of orthopedic surgeons depends highly on the information they receive and whether it is specialized and consistent, as this will condition their acceptance and implementation of the bioprinted cartilage.
The cartilage is a specialized connective tissue that does not contain nerves, blood, or lymphatic vessels and is formed by the differentiation of mesenchymal cells. It is flexible and composed mainly of extracellular matrix that contains chondrocytes. Defects on the articular cartilage do not heal spontaneously and tend to develop into osteoarthritis, which in turn alters the articular function and can cause disability and progressive loss of quality of life [
The development of regenerative medicine and tissue engineering–oriented techniques may contribute to the knowledge of the field of joint injuries. This, in turn, could lead to better articular disease treatment techniques and resolve the clinical problem of healing critical size articular osteochondral defects [
The key elements of tissue engineering are tissue-forming cells, structural scaffolds, and signaling molecules, the combination and application of which result in a functional tissue construct to promote tissue healing and regeneration [
Autologous chondrocytes could be an obvious choice for regeneration of articular cartilage injuries. However, traditional treatments based on chondrocytes have identified several drawbacks of such chondrocytes: (1) they have a low rate of proliferation; (2) although it is easy to isolate them, the number of obtainable cartilage cells is limited; and (3) there are implications for morbidity of the donor site. Consequently, the use of other cell types for different tissue engineering applications such as stem cells [
Regenerative medicine [
Bioprinting [
In an animal study, Di Bella and collaborators [
Implementation research [
This study aims to understand how orthopedic surgeons make clinical decisions and to assess their knowledge and opinion on this topic as well as their needs concerning the bioprinted cartilage graft.
Two main goals were set: (1) to obtain a better understanding of the orthopedic surgeons’ decision-making process, and, by using this knowledge, to understand which factors would drive surgeons to use the graft on the treatment of cartilage lesions and (2) to identify surgeons’ expectations regarding the use of grafts and the key factors to be addressed for surgeons to consider implantation of such grafts on a patient. Hence, the overall purpose was to define the ideal scenario and characteristics of the graft for successful implantation.
This survey and its questions were defined in the context of both a previous qualitative study [
Approval was obtained from the Committee of University Research from a University of Vic - University Central of Catalonia (registration number 28/2017).
Participants of the study were informed that the survey was anonymous and notified about the average completion time, and all information mentioned in the survey was credited to its source. The results were stored on a university-owned website, with private access for the authors.
Before the final version of the survey was sent, a trial version was sent to 17 orthopedic surgeons to ensure that both the subject and the instructions were understood and to measure the average time for completion. After the results were obtained, some changes were introduced in the survey: questions that asked to rate agreement were scored on 10 possible scores instead of 5 possible scores, adding more options; the writing of the questions and answers was edited; and more specific questions were added.
The final questionnaire, with 25 self-managed questions, allowed identification of the decision-making patterns of orthopedic surgeons. The constituent elements of the questionnaire are configured in five domains: (1) demographic questions, (2) information and knowledge of 3D printing, (3) knowledge about the graft’s qualities, (4) knowledge about the expectations for this new technology, and (5) scientific evidence and clinical trials.
The Col·legi de Metges de Barcelona (the Medical Association of Barcelona) has 1081 currently active orthopedic surgeons registered, including 906 men (83.8%) and 175 women (16.2%). Of the members, a total of 849 also belong to the Catalan Society of Orthopedic and Traumatology Surgery (SCCOT), which is a nonmandatory affiliation. An email was written to all SCCOT surgeons, asking them to participate in the study, with a survey link. Of these, 72 emails were returned to the sender (the email address was wrong), and 777 orthopedic surgeons received the email.
In Spain, orthopedic surgeons can develop their work in the public and private sector at the same time. The specialization in sports orthopedics is not separately regulated. Because the survey was anonymous, we could not determine how many of the respondents were from the academic field.
The survey was voluntary, had no incentives, consisted of only one page, and allowed for review of the answers before sending. Answers could be easily obtained and homogenized, as they were in the same order, level, and presentation within all instances, which reduced the error margin and facilitated data retrieval.
The response rate was 11% (86/777). The average time to completion was 15.43 minutes. The survey was kept active until a sufficient number of answers were collected.
The calculation of the size of the finite sample was obtained using the Murray and Larry [
IBM SPSS Statistics software for Windows, version 21.0 (IBM Corp, Armonk, New York), was used to analyze the answers of the survey. The Kolmogorov-Smirnov test was used to evaluate the homogeneity of the data. A descriptive analysis with the distribution of frequencies, averages, and SDs was conducted. A comparative analysis was conducted using the Kruskal-Wallis test, Mann-Whitney
The results have been categorized into two blocks: the information that affects the decision-making process of orthopedic surgeons and the qualities that a graft should ideally have, to be implanted in patients.
Participants were first asked about their gender, age, experience, and type of hospital where they practiced surgery (
Hospitals in Spain can be classified as low, medium, or high complexity depending on the type of technology they use and the type of medical assistance they offer. Research and teaching are conducted at medium- and high-complexity hospitals.
The main aspect of implementation research is evaluating and determining the level of information specialists need to acquire in order to implement the new technology. To obtain a better understanding of the information orthopedic surgeons depend upon to make decisions, answers have been classified by type and origin of the information, relevance, level of acceptance of new technologies, and how the technology is related to age, place, and years of experience.
Participants were asked if they had received any type of information related to new medical applications and 3D printing (
Almost 70% of the surveyed participants reported that they have received information related to new medical applications and 3D printing via any medium. They considered themselves updated in the medical applications of new technologies as per their own perception.
Demographic data of the participants (N=86).
Demographic | Surgeons, n (%) | |
Women | 32 (37) | |
Men | 54 (63) | |
<40 years | 27 (31) | |
40-50 years | 14 (16) | |
>50 years | 45 (52) | |
5-15 years | 33 (38) | |
15-30 years | 28 (33) | |
>30 years | 25 (29) | |
Yes | 80 (93) | |
No | 6 (7) | |
Hospital of low complexity | 16 (19) | |
Hospital of medium complexity | 34 (40) | |
Hospital of high complexity | 36 (42) |
Information received and new technologies updates.
Source of information | Value | |
Yes | 60 (70) | |
No | 26 (30) | |
Reported scores (range) | 2-10 | |
Mean (SD) score | 6.88 (1.66) |
From the previous question, the relevance of the information was analyzed. Relevance was determined by the effect information had in making surgeons feel more and better informed.
To evaluate the relevance, the source of information was analyzed. We analyzed whether those who had received information (by any medium; n=60) considered themselves better informed than the rest and whether those who had received information from specialized companies (n=20) had more knowledge than those who had not received any such information (
Crossing the two variables from the previous
Regarding the bioprinted cartilage graft specifically, participants who received information on the medical application of 3D printing (n=60) and considered themselves informed (mean 6.27, SD 1.99) were asked how specific and from which source the information they had received on bioprinted cartilage was (
Of the 60 participants who received general information on 3D printing, only 27 (45%) knew about bioprinted cartilage, and the information had been acquired from their colleagues (18%) or the scientific literature (27%).
Level of self-perceived knowledge on 3D printing in relation to the information received (N=86).
Source of information | Surgeons, n (%) | Mean (SD) | |||
Yes | 60 (70) | 6.27 (1.99) | |||
No | 26 (30) | 4.69 (1.73) | |||
Yes | 20 (23) | 6.95 (1.76) | |||
No | 66 (77) | 5.44 (2) |
aMann-Whitney
b
Means of learning about bioprinted cartilage among participants who received information on 3D printing (Question: If you have received any 3D printing information regarding bioprinted cartilage, through which channel was it? N=60).
Means of learning | Surgeons, n (%) |
Through other colleagues | 11 (18) |
I read a lot of new research | 16 (27) |
I read a little new research | 2 (3) |
I have no information about it | 30 (50) |
I’m not interested in it | 1 (2) |
To determine if there was a relationship between the relevance of the information received and the acceptance of new technologies, we analyzed the acceptance level of the bioprinted cartilage graft among participants who had higher self-perceived knowledge (20/86) and had received the information from specialized 3D companies (
Regarding the perception or ease of acceptance of the bioprinted cartilage graft, there was a significant difference between participants who were informed by specialized companies and those who were not (
To define if the process of decision-making by orthopedic surgeons could be linked to their demographic data, three variables were analyzed: age, years of experience, and place of experience (
Considering self-perceived knowledge, the only difference identified was in the age of the participants. Participants aged over 50 years (38/86) considered themselves to be significantly more informed on new technologies than those of other age groups (
Surgeons’ acceptance of the use of bioprinted cartilage grafts for their patients, according to the source of information (Question: If the researchers/biotech industry could give us a cartilage graft made with bioprinting, would you think about the convenience of using it in your patients? N=86).
Source of information | Surgeons, n (%) | Mean (SD) | |||
Yes | 20 (23) | 8.40 (1.53) | |||
No | 66 (77) | 7.53 (1.69) | |||
Yes | 60 (70) | 7.65 (2.38) | |||
No | 26 (30) | 7.92 (1.41) |
b
Influence of demographic data of orthopedic surgeons on the knowledge of new technologies (Do you consider yourself up to date regarding new technologies emerging in the medical field? N=86).
Demographic | Surgeons, n (%) | Mean (SD) | |||||
<40 years | 28 (33) | 6.5 (1.79) | |||||
40-50 years | 20 (23) | 7.2 (1.85) | |||||
>50 years | 38 (44) | 7 (1.45) | |||||
5-15 years | 33 (38) | 6.42 (1.88) | |||||
15-30 years | 28 (33) | 7.14 (1.55) | |||||
>30 years | 25 (29) | 7.2 (1.38) | |||||
Hospital of low complexity | 16 (19) | 6.94 (1.48) | |||||
Hospital of medium complexity | 34 (40) | 6.91 (1.65) | |||||
Hospital of high complexity | 36 (42) | 6.83 (1.79) |
aKruskal Wallis test.
b
The second goal of this study was to identify the qualities of the ideal cartilage graft for application by the orthopedic surgeons in relation to patient characteristics, type of lesion, and perceived difficulties of their use.
The essential characteristics of the bioprinted graft that were analyzed to identify the suitable age of the patient for the implantation, ideal size of the lesion, and duration of the graft. Participants were also asked to choose the most relevant of five suggested qualities (
Regarding the age of the patient, 50% of the participants would not implant the graft on patients aged over 70 years, whereas 42% of them did not consider age to be a delimitating factor. Most of them (62%) considered the ideal size of the injury to be between 1 and 2 cm for implantation of a bioprinted cartilage graft. However, 27 (31%) of participants would consider such grafts for lesions over 3 cm. Almost all participants would reject a graft that lasted less than a year. Moreover, 51 of them (59%) said they would not recommend the graft to the patient unless it lasted more than 5 years.
Of the suggested qualities, the two most often selected (78%) were duration of the graft and patient safety (no side effects to general health). One less-often selected quality was ease of implantation, only considered by 50% of the participants.
The link between the perception in relation to the difficulties and the type of hospital was examined to determine if perceived difficulties were related to surgeons’ place of work or whether it was the individual perception of the orthopedic surgeon (
The main difficulties considered by orthopedics in low-complexity hospitals were outcome uncertainty (ie, lack of clinical trials that prove successful outcomes) and authorization issues by the hospital management. In medium-complexity hospitals, surgeons shared these worries, although to a lesser extent. In high-complexity hospitals, however, the main issue was patient safety, followed by outcome uncertainty.
Determining factors of the archetype graft (N=86).
Factor | Surgeons, n (%) | |
I do not see any age limitation | 36 (42) | |
Under 20 years of age | 7 (8) | |
Over 70 years of age | 43 (50) | |
<1 cm | 6 (7) | |
1-2 cm | 53 (62) | |
>3 cm | 27 (31) | |
<1 year | 6 (7) | |
1-5 years | 29 (34) | |
>5 years | 51 (59) | |
Durability in time | 67 (78) | |
Safety for the patient | 67 (78) | |
Good clinical results | 58 (67) | |
Affordable price | 54 (63) | |
Reliable evidence | 55 (64) | |
Ease of surgical implementation | 43 (50) |
Perceived difficulties with bioprinted cartilage according to place of work (What problems/difficulties do you perceive for its use/work placement? Multiple choices possible)
Difficulty | Surgeons, n (%) | Surgeons in hospitals of low complexitya, n (%) | Surgeons in hospitals of medium complexityb, n (%) | Surgeons in hospitals of high complexityc, n (%) |
Uncertainty in results | 61 (71) | 11 (18) | 23 (38) | 27 (44) |
Authorization by the hospital | 50 (58) | 11 (22) | 16 (32) | 23 (46) |
Patient safety | 46 (53) | 10 (22) | 16 (35) | 30 (65) |
Hard to handle | 38 (44) | 6 (16) | 15 (39) | 17 (45) |
Waiting time | 37 (43) | 8 (22) | 13 (35) | 16 (43) |
Surgical difficulties | 31 (36) | 7 (23) | 9 (29) | 15 (48) |
a16 surgeons were from hospitals of low complexity (19% of the 86 participants).
b34 surgeons were from hospitals of medium complexity (40% of the 86 participants).
c36 surgeons were from hospitals of high complexity (42% of the 86 participants).
Once the qualities of the graft were defined, their consequences on the patient’s life were highlighted, from pain reduction to improvement in the quality of life (everyday life satisfaction). Participants were also asked about the need for clinical trials. These data were crossed with the source of information, via any medium or specialized companies, and with the age of the surgeon, as it was previously observed that it was the only relevant demographic variable (
No significant differences were observed in terms of the importance of pain reduction, which was considered by all participants as a necessary requisite. Surgeons who had received information via any medium were more pessimistic regarding the positive effects or positive impact the bioprinted cartilage graft could have on the patients’ quality of life (
Correlation of variables for the use of a bioprinting cartilage, the need for clinical trials, and age of surgeons.
Variable | Number of surgeons (%) | Mean (SD) | ||||
Yes | 20 (23) | 8.9 (9.96) | ||||
No | 66 (77) | 8.44 (1.83) | ||||
Yes | 60 (70) | 7.53 (1.67) | ||||
No | 26 (30) | 8.27 (1.25) | ||||
Yes | 20 (23) | 8.45 (1.07) | ||||
No | 66 (77) | 7.60 (1.63) | ||||
Yes | 60 (70) | 8.78 (1.71) | ||||
No | 26 (30) | 8.77 (1.53) | ||||
<40 years | 28 (33) | 8.65 (1.87) | ||||
40-50 years | 20 (23) | 8.35 (1.18) | ||||
>50 years | 38 (44) | 9.16 (1.58) |
aMann-Whitney
b
c
Most of the participants highlighted the need for clinical trials, irrespective of the source of information. When the need for clinical trials and the age of the surgeons were crossed, it was clear (
There are a few studies published on the perspective of orthopedic surgeons on the bioprinting cartilage, since it is not yet on the market, but there is research on 3D printed medical implants [
Recent studies represent a significant advance in the clinical translation of human cartilage and the appropriate surgical procedure. The focus of the research is on the biofabrication of biomaterials that maintain the biocompatibility and biodegradability of the original cartilage while increasing the efficiency of cell growth [
Although researchers are moving forward in all fields of cartilage bioprinting, we have not been able to find working groups publishing the issues of implementation, and therefore, knowledge of orthopedic surgeons on this topic is scarce.
In our previous research [
The results of this study show that the information received impacts the decision-making process of orthopedic surgeons in a complex and diverse way, as it depends on several variables: the type and origin of the information and its relevance to their demographic data. Previous research [
Therefore, it could be argued that specialized companies should work closely with orthopedic surgeons to help them acquire more specialized knowledge [
The second set of goals was to analyze the factors that would provide the ideal context and qualities of an archetypal bioprinted cartilage graft as well as factors perceived as difficulties. The characteristics listed on the survey were size of the lesion, duration of the graft, and age of the patient (
For the perceived difficulties in the use of the bioprinted cartilage graft (
It was expected that other difficulties linked to practical aspects, such as the hospital management’s authorization to use the technique and the wait time for the graft, would be linked to the type of hospital. Therefore, in medium-complexity hospitals, authorization is less problematic than either of the two abovementioned aspects: There is not as much bureaucracy involved in medium-complexity hospitals as in a high-complexity hospital, and new technologies are more easily accepted than they are in smaller hospitals. Finally, the need for clinical trials is one of the main difficulties for implementation of the technique (
The present study should be interpreted in the context of its limitations. The initial proposal planned to cover the entirety of the Spanish territory, through the Spanish Society of Orthopedic and Traumatology Surgery and the Spanish Society of the Knee, and English-speaking specialists through the International Cartilage Research Society, but it was not possible to receive authorization from these societies to send the survey. Our coverage of only a small population is a big limitation, as is the low response rate. In addition, there could be a bias, since the participants who answered the survey were probably more interested in the application of new technologies. Finally, the Chi-squared test might provide inexact results when the values input are small.
The process of decision-making is based on precise information of quality, provided by companies specializing in the medical application of 3D printing. This variable seems essential to the acceptance of new technologies. The ideal graft, as described by surgeons, could provide important insight to researchers, at least in the initial stages of development, to satisfy the expectations of surgeons. Implementation research should focus on two variables: ensuring communication flows from researchers to surgeons and ensuring that the opinions of orthopedic surgeons regarding the qualities and issues of the grafts reach researchers, which would help them implement the bioprinted cartilage graft with success.
Catalan Society of Orthopedic and Traumatology Surgery
We thank the Catalan Society of Orthopedic and Traumatology Surgery, and specially its President, Pere Torner, for the help provided to distribute the survey. We also thank Ismael Cerdà for reviewing the survey and Marina Mustieles for her help in the translation of this text.
This study has not been funded by any institution or organization.
ASV conducted the study and data analysis with the help of MY and FLS. The other authors contributed to the writing and editing of the manuscript. All authors read and approved the final version of the manuscript.
None declared.