
==== Front
Heliyon
Heliyon
Heliyon
2405-8440
Elsevier

S2405-8440(24)12751-X
10.1016/j.heliyon.2024.e36720
e36720
Research Article
Global research trends of antibiotic-loaded bone cement: A bibliometric and visualized study
Chen Peisheng a1
Chen Bin a1
Liu Nannan b1
Lin Xiaofeng a
Wei Xiaojuan c
Yu Bin d
Teng Xing drtengx@163.com
e⁎2
Lin Fengfei 596558644@qq.com
a⁎⁎2
a Department of Orthopedics, Fuzhou Second General Hospital, School of Clinical Medicine, Fujian Medical University, Fujian Provincial Clinical Medical Research Center for First Aid and Rehabilitation in Orthopedic Trauma, Fuzhou, 350007, Fujian, People's Republic of China
b Department of Orthopedics Institute, Fuzhou Second General Hospital, Fuzhou, 350007, Fujian, People's Republic of China
c Department of Pharmacy, Fuzhou Second General Hospital, Fuzhou, 350007, Fujian, People's Republic of China
d Division of Orthopedics & Traumatology, Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China
e Department of Orthopedic Trauma, Beijing Jishuitan Hospital, Capital Medical University, Beijing, 100035, People's Republic of China
⁎ Corresponding author. Department of Orthopedic Trauma, Beijing Jishuitan Hospital, Capital Medical University, Beijing, 100035, People's Republic of China. drtengx@163.com
⁎⁎ Corresponding author. Department of Orthopedics, Fuzhou Second General Hospital, School of Clinical Medicine, Fujian Medical University; Fujian Provincial Clinical Medical Research Center for First Aid and Rehabilitation in Orthopedic Trauma, Fuzhou, 350007, Fujian, People's Republic of China. 596558644@qq.com
1 Peisheng Chen, Bin Chen and Nannan Liu contributed equally to this work and share the first authorship.

2 Xing Teng and Fengfei Lin contributed equally to this work and share the last authorship.

22 8 2024
15 9 2024
22 8 2024
10 17 e367203 4 2024
20 8 2024
21 8 2024
© 2024 The Authors. Published by Elsevier Ltd.
2024

https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Objective

Antibiotic-loaded bone cement (ALBC) plays an indispensable role in the treatment of infectious diseases of bone and joint. Here, we intended to analyze the research status, hot spots and frontiers in the field of ALBC, and to provide reference for future research ideas.

Methods

The related English literature in the field of ALBC in the Web of Science Core Collection database was retrieved from January 1, 2009 to July 11, 2023. VOSviewer was used to extract the information of research constituents or bibliometric items such as authors, institutions, countries, and journals. CiteSpace was used to perform cluster analysis and frontier analysis of key words in ALBC research field.

Results

A total of 1091 literatures related to ALBC research were retrieved, and the annual number of publications showed a steady upward trend in the past 15 years. The high-yield countries and regions are mainly represented by the United States, China (including Taiwan, China) and several European countries, such as Germany, England, Spain, Italy, the Netherlands, etc. The top three institutions with the highest number of publications were Shanghai Jiao Tong University, Chang Gung University and Chang Gung Memorial Hospital in China. Four of the top 10 influential scholars come from Germany, namely Konstantinos Anagnostakos, Volker Alt, Andrej Trampuz, and Bernd Fink. The top 10 high-yield journals had an average of 25 articles per journal and an average of 618.9 citations. The top 3 high-yield journals were Journal of Arthroplasty (57 articles, 1213 citations), Clinical Orthopaedics and Related Research (35 articles, 1119 times cited), and Journal of Orthopaedic Research (29 papers, 488 times cited). The keywords with high frequency were infection (266 times), vancomycin (239 times), bone-cement (219 times), gentamicin (216 times), antibiotics (168 times), osteomyelitis (163 times), etc. The clustering knowledge map of high-frequency keywords could be divided into 4 categories: (1) elution, release, mechanical and antibacterial properties of ALBC; (2) Application of ALBC in revision of prosthetic joint infections (PJIs); (3) Antibiotic types and application forms of ALBC; (4) Application of ALBC in the treatment of osteomyelitis. The keywords with the strongest citation bursts analysis revealed a core ("replacement/arthroplasty") and two stages of development in the field of ALBC research. The first stage (2009–2018) focused more on ALBC drug delivery, release, and infection prevention, while the second stage (2018–2023) mainly focused on ALBC drug elution, mechanical properties, and PJIs revision. Starting from 2018, the keyword with the strongest citation bursts had shifted from "acrylic bone cement" to "periprosthetic joint infection".

Conclusion

ALBC research is steadily on the rise. Arthroplasty related applications continue to be the core of ALBC research. The research hotspot and trend are mainly the application in the prevention and treatment of bone and joint infectious diseases and the elution, release, mechanical and antibacterial properties of ALBC.

Keywords

Polymethylmethacrylate
Antibiotic-loaded bone cement
Prosthetic joint infections
Fracture-related infections
Bibliometrics
Visualized analysis
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pmc1 Introduction

Bacterial infections are one of the most devastating complications in orthopedic surgery, especially prosthetic joint infections (PJIs) and fracture-related infections (FRIs), often leads to severe impact on limb function, quality of work and standard of living [1].

Traditional treatments include debridement surgery and intravenous antibiotics. However, there are still some problems, such as poor infection control or bone defects caused by repeated debridement, recurrent infections due to unstable antibiotic concentration or insufficient local bacteriostatic concentrations. Polymethylmethacrylate (PMMA), also known as bone cement or acrylic bone cement, is a non-degradable biomaterial that provides bone support and stability. Meanwhile, antibiotic-loaded PMMA or antibiotic-loaded bone cement (ALBC) can act as a local antibiotic carrier and play an important role in the prevention and treatment of orthopedic infections [2].

Methylmethacrylate (MMA) is the main component of PMMA, which is formed by free radical polymerization. Other components include inhibitors, colorants, antibiotics, and additives that regulate the polymerization process. In clinical application of ALBC, usually by mixing powder and liquid two ingredients, PMMA will gradually change from doughy to solid. During the curing process, it can be shaped and prepared into chain beads, spacers or encapsulated plants. The cured ALBC has certain mechanical properties, which can not only enhance the stability of endoplant fixation, fill anatomical cavities or provide support function, but also play a certain role in anti-infection.

Bibliometrics can transform a large number of documents into knowledge maps, which is conducive to exploring research hotspots and innovative methods efficiently and intuitively [3]. The database Web of Science Core Collection (WoSCC) (https://www.webofscience.com/wos/) is commonly used to perform bibliometric analysis to track the evolution of scientific disciplines. Due to its recognized ability to provide standardized and high-quality academic published data, this study conducted a comprehensive online exploration of the WoSCC database. In this study, the knowledge mapping software VOSviewer and CiteSpace were applied to analyze and visualize the relevant data from the WoSCC database, explore the research status and hot spots of ALBC, and forecast its future research trend, in order to provide certain references for in-depth research in this field.

2 Materials and methods

2.1 Data collection and search methodology

The main focus of this study is ALBC-related research articles and reviews in English. The search strategy of the WoSCC database was presented as follows: TS = ((Antibiotic or “Anti-Bacterial Agents”) AND (PMMA or “polymethyl methacrylate” OR “bone cement” OR “PMMA cement” OR “PMMA-cement”)). The search covered publications from January 1, 2009 to July 11, 2023. The two authors (P. Chen, B. Chen) conducted the literature search independently and then sorted out and summarized the literature. Data cleaning was performed for duplicate and erroneous entries in the published papers. The disputes were confirmed through negotiation with the third author (N. Liu). VOSviewer 1.6.15 (Leiden University, Netherlands) and CiteSpace V5.6.R5 (Drexel University, USA) were used for bibliometric and visualized analysis of research status, hot spots and trends.

2.2 Research methods and observation indicators

Firstly, VOSviewer was used to extract the information of research constituents or bibliometric items such as authors, institutions, countries, and journals. CiteSpace was combined to analyze the hot keywords and research frontiers of ALBC research. It included six observation indicators. (1) The basic information of the included literatures. (2) Analysis of high-yield countries, regions, institutions, and authors: Selected the analysis type as “Coauthorship” in the VOSviewer software, and the analysis units were “Countries”, “Organization”, and “Authors” respectively to analyzed the number of papers published by different countries, regions, institutions, and authors. (3) High-yield journal analysis: Selected “citations” as the analysis type and “sources” as the analysis unit in VOSviewer software to analyzed the number of publications in different cited journals. (4) Highly cited literature analysis: Selected the analysis type as “Co-citation” and the analysis unit as “Cited references” in VOSviewer software to analyzed the development and evolution of ALBC research field, and determined the core literature in this field. (5) Keyword analysis: Set the analysis type as “Co-occurrence” and the analysis unit as “All keywords” in the VOSviewer software, set the occurrence frequency of keywords ≥30 times, and performed cluster analysis on the obtained high-frequency keywords. (6) Frontier analysis: Selected keyword burst analysis in Citespace software, set buest intensity ≥4.

2.3 Statistical analysis

Microsoft Excel office 2010 (Microsoft Corporation, Redmond, USA) was used to draw the publication trend chart of ALBC research, and the exponential trend line function was used to fit the overall publication trend. All information obtained was descriptive data.

3 Results

3.1 Annual distribution and trend of the number of publications

A total of 1091 articles were included (Fig. 1). In the past 15 years, the annual number of papers published in this field has shown a steady upward trend, with more than 50 papers published each year, of which the highest number of papers published in 2020, followed a short decline. The exponential trend forecast line indicates that the number of publications will gradually rise to 101 in 2028 (Fig. 2).Fig. 1 Flow chart of document retrieval.

Fig. 1

Fig. 2 Publication trend of ALBC research.

Fig. 2

3.2 Analysis of productive countries, regions, institutions, and authors

The productive countries and regions in ALBC research are primarily represented by the United States, China (including Taiwan, China), and several European countries, such as Germany, the United Kingdom, Spain, Italy, and the Netherlands (Table 1). The top 10 institutions include Shanghai Jiao Tong University from China, Chang Gung University (Taiwan), Chang Gung Memorial Hospital (Taiwan), the University of Memphis and the Hospital for Special Surgery from the United States, Thomas Jefferson University, the University of Würzburg and Heraeus Medical GmbH from Germany, the University of Lisbon from Portugal, and the AO Research Institute in Davos, Switzerland (Table 2). The top 10 influential scholars in ALBC research include Konstantinos Anagnostakos, Volker Alt, Andrej Trampuz, and Bernd Fink from Germany, Joseph C. Wenke and Antonios G. Mikos from the United States, Daniëlle Neut, Henk J Busscher, and Henny C van der Mei from the Netherlands, and António J Almeida from Portugal (Table 3). It can be seen from the above that there is a significant amount of ALBC research conducted in the United States, China, and European countries represented by Germany, and there is close collaboration among many institutions and scholars in Europe and America (Fig. 3, Fig. 4, Fig. 5).Table 1 Top 10 productive countries and regions in ALBC research.

Table 1No	Country and Region	Number of Publications	Citation Frequency	Total Link Strength	
1	USA	312	7669	111	
2	China	168	4480	26	
3	Germany	119	2745	56	
4	England	74	1769	52	
5	Spain	45	983	20	
6	Italy	43	1167	22	
7	Taiwan, China	43	932	6	
8	Canada	38	1177	32	
9	India	38	932	13	
10	Netherlands	36	1559	20	

Table 2 Top 10 productive institutions in ALBC research.

Table 2No	Institution	Country or Region	Number of Publications	Citation Frequency	Total Link Strength	
1	Shanghai Jiao Tong Univ	China	20	993	22	
2	Chang Gung Univ	Taiwan, China	18	533	28	
3	Chang Gung Mem Hosp	Taiwan, China	16	581	21	
4	Univ Memphis	USA	14	377	39	
5	Univ Wurzburg	Germany	13	499	14	
6	Univ Lisbon	Portugal	13	333	22	
7	Hosp Special Surg	USA	13	228	26	
8	Heraeus Med GmbH	Germany	12	251	15	
9	Thomas Jefferson Univ	USA	12	173	35	
10	AO Res Inst Davos	Switzerland	11	828	35	

Table 3 Top 10 productive authors in ALBC research.

Table 3No	Author	Country	Number of Publications	Citation Frequency	Total Link Strength	
1	Anagnostakos, Konstantinos	Germany	10	499	13	
2	Wenke, Joseph C.	USA	9	367	19	
3	Alt, Volker	Germany	9	144	43	
4	Neut, Danielle	Netherlands	8	405	20	
5	Busscher, Henk J.	Netherlands	8	393	20	
6	Van Der Mei, Henny C.	Netherlands	8	393	20	
7	Mikos, Antonios G.	USA	8	321	45	
8	Almeida, Antonio J.	Portugal	8	269	40	
9	Trampuz, Andrej	Switzerland/Germany	8	106	24	
10	Fink, Bernd	Germany	6	289	5	

Fig. 3 Co-occurrence map of countries and regions in ALBC research.

Fig. 3

Fig. 4 Co-occurrence map of institutions in ALBC research.

Fig. 4

Fig. 5 Co-occurrence map of authors in ALBC research.

Fig. 5

3.3 Analysis of high-impact journals

The average Impact Factor (IF) for the top 10 high-impact journals in 2024 is 3.32 (ranging from 2.1 to 4.9), with 5 journals in Q1, 5 journals in Q2. Half of the top 10 high-impact journals are published in the United States. The top 10 high-impact journals published a total of 250 articles, and the top 4 journals accounted for 58.8 %. In addition, the average number of citations of these 10 journals was 618.9 times. The top three are Journal of Arthroplasty, Clinical Orthopaedics and Related Research, and Journal of Orthopaedic Research. ALBC research has attracted attention from disciplines such as bone and joint diseases, biomaterials, antibiotics, and nursing (Table 4).Table 4 Top 10 high-impact journals in ALBC research.

Table 4No	Journal	IF (2024.06.20)	Publishing Country	Number of Publications	Citation Frequency	Total Link Strength	
1	Journal of Arthroplasty	3.4/Q1	USA	57	1213	451	
2	Clinical Orthopaedics and Related Research	4.2/Q1	USA	35	1119	204	
3	Journal of Orthopaedic Research	2.1/Q2	USA	29	488	217	
4	Journal of Biomedical Materials Research Part B-Applied Biomaterials	3.2/Q2	USA	26	673	170	
5	Injury-International Journal of the Care of the Injured	2.2/Q2	Netherlands	22	923	98	
6	Bone & Joint Journal	4.9/Q1	England	18	521	150	
7	Antibiotics-Basel	4.3/Q1	Switzerland	18	51	112	
8	BMC Musculoskeletal Disorders	2.2/Q2	England	16	143	73	
9	Journal of Materials Science-Materials in Medicine	4.2/Q2	USA	15	366	65	
10	Acta Orthopaedica	2.5/Q1	Sweden	14	692	94	
IF, Impact Factor, a quantitative index to describe the impact of journals.

3.4 Analysis of highly-cited literature

Table 5 is the analysis of the reference lists of the included articles. Additionally, Table 5 shows the top 10 most-cited research papers in the field of ALBC, including 6 articles, 3 reviews, and 1 meta-analysis. Among the 6 articles, 5 focus on the combination, ratio, in vivo and in vitro elution kinetics of antibiotics such as vancomycin, tobramycin, and gentamicin, as well as their effects on the compressive strength and fatigue life of bone cement. Other articles review the effectiveness and safety of ALBC in the prevention and treatment of PJIs.Table 5 Highly-cited literature in ALBC research (top 10 analysis of the reference lists of the included articles).

Table 5No	Title	Journal	First author	Year	Citation Frequency	Total Link Strength	
1	Antibiotic-loaded bone cement for infection prophylaxis in total joint replacement	The Journal of Bone and Joint Surgery. American Volume	William A Jiranek	2006	136	1670	
2	Depot effects of various antibiotics mixed with Palacos resins	Der Chirurg; Zeitschrift für alle Gebiete der operativen Medizen	H W Buchholz	1970	108	1203	
3	Elution characteristics of vancomycin and tobramycin combined in acrylic bone-cement	Journal of Arthroplasty	M J Penner	1996	103	1433	
4	Long-term elution of antibiotics from bone-cement: an in vivo study using the prosthesis of antibiotic-loaded acrylic cement (PROSTALAC) system	Journal of Arthroplasty	B A Masri	1998	94	1251	
5	Antibiotic-impregnated cement spacers for the treatment of infection associated with total hip or knee arthroplasty	The Journal of Bone and Joint Surgery. American Volume	Quanjun Cui	2007	91	1103	
6	Surface roughness, porosity and wettability of gentamicin-loaded bone cements and their antibiotic release	Biomaterials	H van de Belt	2000	84	1044	
7	Prosthetic-joint infections	The New England Journal of Medicine	Werner Zimmerli	2004	79	695	
8	The use of vancomycin and tobramycin in acrylic bone cement: biomechanical effects and elution kinetics for use in joint arthroplasty	Journal of Arthroplasty	J Klekamp	1999	68	931	
9	Efficacy of antibiotic-impregnated cement in total hip replacement	Acta Orthopaedica	Javad Parvizi	2008	68	832	
10	Antibiotic prophylaxis in total hip arthroplasty: effects of antibiotic prophylaxis systemically and in bone cement on the revision rate of 22,170 primary hip replacements followed 0–14 years in the Norwegian Arthroplasty Register	Acta orthopaedica Scandinavica	Lars B Engesaeter	2003	66	693	

3.5 Keyword analysis

A total of 67 keywords were included. The keywords with higher frequency of occurrence include infection (266 times), vancomycin (239 times), bone-cement (219 times), gentamicin (216 times), antibiotics (168 times), and osteomyelitis (163 times). The high-frequency keyword cluster knowledge map of ALBC research is shown in Fig. 6 and can be divided into four categories: (1) the elution/release/mechanical/antimicrobial properties of ALBC; (2) the application of ALBC in PJIs revision; (3) the types and forms of antibiotics used in ALBC; (4) the application of ALBC in the treatment of osteomyelitis.Fig. 6 High-frequency keyword cluster network map of ALBC research.

Fig. 6

3.6 Frontier analysis

Frontier analysis could find keywords with high burst intensity in different time periods, which could indicate the development trend of the research field and predict potential research hotspots. A total of 17 burst words were finally included (Fig. 7). The ALBC research field can be divided into two stages: 2009–2018 and 2018–2023. Arthroplasty (or replacement) serves as the core axis of ALBC research throughout. In the first stage (2009–2018), drug delivery, release, and infection prevention of ALBC received relatively extensive attention and practice. Starting from 2018, the word with the highest burst intensity in the ALBC research field shifted from "acrylic bone cement" to "periprosthetic joint infection (PJI)". In the second stage (2018–2023), the hot topics of ALBC research mainly focused on drug elution, mechanical properties, and PJIs revision.Fig. 7 Burst word analysis of ALBC research.

Fig. 7

4 Discussion

ALBC is increasingly gaining the attention of scholars for its applications in the prevention of infections in joint replacement surgeries, revision of PJIs, and the surgical treatment of infectious bone defects and non-unions. By utilizing the Web of Science database and employing bibliometric analysis software such as VOSviewer and CiteSpace, the current state, research hotspots, and development trends of ALBC research can be objectively described. This multi-angled visualization analysis serves as a reference for subsequent researchers to quickly grasp key areas and ideas in ALBC research.

4.1 Overview of ALBC research

ALBC, prepared by mixing PMMA and antibiotics, is widely used for the prevention and treatment of FRIs and PJIs through the sustained release of the loaded antibiotics. The productive authors, institutions, and countries can lead and promote the rapid development of ALBC research field. This study indicates that European and American countries are leading in the field of ALBC research, with Germany being particularly representative. Notably, the University of Würzburg, Heraeus Medical GmbH in Germany, and scholars such as Konstantinos Anagnostakos, Volker Alt, Andrej Trampuz, and Bernd Fink have made significant contributions to ALBC research. Initially, ALBC was used only for the prevention of bacterial infections. In 1972, Buchholz and colleagues from Hamburg, Germany, were the first to apply it for the treatment of deep-seated infections in total hip prostheses [4]. Among the highly-cited literature, Buchholz's 1970 German publication on the "inventory effect of different antibiotics combined with Palacos resin" ranks second in this analysis. It is also worth noting that Shanghai Jiao Tong University, Chang Gung University (Taiwan), and Chang Gung Memorial Hospital (Taiwan) from China have established a presence in the field of ALBC research. The high-frequency keywords in ALBC research mainly cluster into two aspects: (1) applications in the treatment of PJIs and FRIs; (2) various types/applications/forms of antibiotics, elution, release, mechanics, and antimicrobial properties. The former leans towards clinical applications, while the latter towards basic research. Similarly, the analysis of highly-cited literature primarily focuses on the combinations, ratios, elution dynamics of different antibiotics, and their effects on the mechanical strength and service life of bone cement. Reviews and meta-analyses mainly clarify the effectiveness and safety of ALBC in the prevention and treatment of PJIs. Similar information is also reflected in the "1 + 2″ development context revealed by the burst word analysis.

Through analysis, it can be found that the highly cited literature mainly focused on the combination, ratio, in vitro and in vivo elution kinetics of vancomycin, tobramycin, gentamicin and other antibiotics and their effects on the compressive strength and fatigue life of bone cement. In addition, the efficacy and safety of ALBC in the prevention and treatment of PJIs is also an ongoing hot topic.

4.2 Preparation and application of ALBC

In the preparation of ALBC, antibiotics are typically added to PMMA powder and mixed with a solvent, gradually transitioning from a dough-like state to a solid form. Before solidification, it can be shaped into forms such as beads, spacers, or wrapped implants. The main functions of cured ALBC are twofold: (1) to secure joint prostheses or other implants to the skeleton, enhancing the stability of fixation; (2) to serve as a temporary spacer, filling anatomical cavities, providing support functions, and slowly releasing antibiotics to treat bone and joint infections.

The routine use of ALBC in primary joint replacement surgeries is controversial [[5], [6], [7], [8], [9]]. Although the prophylactic application of ALBC in primary total knee replacement can reduce the incidence of deep PJIs [10], there is a risk of antibiotic resistance and aseptic loosening. Currently, the FDA-approved commercial ALBC products with low antibiotic concentrations are only used in the second stage of two-stage total joint revision surgeries following the removal of the original prosthesis and active PJI control, and may not be suitable for routine primary or uninfected revision cemented joint replacement patients without a high risk of infection [11]. The efficacy of ALBC in PJIs revision is relatively certain. Current PJIs treatment methods include extensive debridement, removal or retention of the prosthesis, including debridement with prosthesis retention, one-stage revision, and two-stage revision, depending on the duration of infection, type of pathogen, soft tissue condition, and patient health status [12]. Debridement with prosthesis retention (DAIR) is usually applied to acute infections within one month of implantation with well-fixed prostheses [13], with a success rate of up to 80 % [14]. Both one-stage and two-stage revisions require extensive debridement and removal of the prosthesis, with the former replacing the prosthesis in one go, and the latter first implanting an ALBC spacer to control the infection before replacing the new prosthesis. The development of antibiotic-loaded joint prostheses is expected to improve the success rate of one-stage revision for PJIs [15], while the success rate of two-stage revision can reach up to 87 %, which is currently the "gold standard" for PJIs treatment [13]. There are certain commonalities in the treatment of FRIs and PJIs, including surgical debridement, systemic or local antibiotic use, and one-stage or two-stage reconstructive surgery. In patients with delayed, systemic symptomatic, difficult-to-treat pathogens, and soft tissue damage, staged treatment is often required. Additionally, ALBC shows promise in the treatment of open fracture bone defects.

4.3 Antibiotic selection for ALBC

Research surrounding antibiotic drug delivery, elution, and release has always been a hot topic in ALBC research. The selection of antibiotics generally has the following five important characteristics [16]: (1) broad-spectrum activity (including Gram-positive and Gram-negative bacteria); (2) low resistance rate; (3) soluble in water; (4) non-allergenic; (5) thermal stability (the exothermic polymerization reaction of cement must not cause changes in the structure and function of the antibiotic). Based on these characteristics, the most commonly mixed antibiotics with PMMA are [2]: (1) gentamicin; (2) tobramycin; (3) vancomycin; (4) clindamycin; (5) erythromycin; (6) ciprofloxacin. Among them, gentamicin and vancomycin are commonly used in Europe, and tobramycin is commonly used in the United States.

When the high concentration of locally released antibiotics in ALBC exceeds the minimal inhibitory concentration (MIC), it can directly act on the infection site, eliminating the pathogen before it forms a protective biofilm. ALBC can be divided into two categories based on the dose of antibiotics mixed with bone cement [16]: high concentration (>2g antibiotic/40g bone cement) and low concentration (<2g antibiotic/40g bone cement). The antibiotic concentration recommended by manufacturers is usually 5 % (w/w) (such as 2g antibiotic/40g bone cement), but the actual load dose also depends on whether ALBC is used for infection prevention or active infection treatment [17]. High-concentration ALBC is typically used as a spacer or prepared in the form of spacers, beads (temporary implants), etc. It is recommended not to use more than 10–15 wt% antibiotics, as this may affect the mechanical properties of bone cement and the stability of the implant. The physical state of the antibiotic can interfere with the curing of PMMA, reducing its mechanical stability, especially liquid antibiotics [18]. Therefore, crystalline antibiotics are preferred in principle. The type of antibiotic is also an important factor, such as rifampicin, which, although in a crystalline state, can inhibit the complete curing of PMMA. ALBC is commonly handmade in clinical practice, with flexible ratios and diverse forms. The mechanical properties of antibiotics and PMMA powder mixed evenly and cured are more balanced, and are expected to provide the maximum antibiotic elution. However, some scholars reserve their opinions on the view that different mixing strategies may lead to differences in the mechanical properties of ALBC [18].

The antibiotic release and elution of ALBC follow a continuous or burst mode. Gentamicin is a typical antibiotic with continuous release kinetics, with a sustained release that hardly declines, while meropenem shows a continuous declining trend over a long period [19]. Vancomycin typically exhibits a burst release, with a high initial release that sharply declines afterward. Moxifloxacin has a longer burst release time than vancomycin. In addition, the following four potential influencing factors need special consideration [2,17,18]: (1) the brand and type of PMMA; (2) the volume, surface area, and their ratio of ALBC: antibiotic elution mainly occurs on the outer layer, and increasing the surface area while matching the lesion's anatomical structure and maintaining the volume of ALBC can increase antibiotic elution, with spheres being superior to cylinders; (3) porosity: processing methods (commercialized/handmade), antibiotic elution, additives, etc.; (4) the type, combination, and ratio of antibiotics: the combined use of antibiotics is expected to produce a synergistic effect, increasing the release of antibiotics and enhancing antimicrobial effects. In dual ALBC (gentamicin + vancomycin), the release of vancomycin and gentamicin increases by 145 % and 45 % respectively [20], and the addition of cefazolin can significantly increase the elution of vancomycin [21].

In summary, the visualization analysis of ALBC-related literature in the Web of Science database effectively reflects the key research directions of ALBC, providing a reference for subsequent in-depth studies on ALBC. Currently, ALBC research is on a steady upward trend. The applications related to joint replacement surgeries remain at the core of ALBC research. The research hotspots and trends mainly focus on the application of ALBC in the prevention and treatment of bone and joint infectious diseases, as well as its elution/release, mechanical, and antimicrobial properties. The conclusions of the articles may be subject to certain biases due to limitations such as analysis tools, content included in the database, and languages. These aspects will be further refined in subsequent research.

Data availability statement

Data associated with this study has been deposited into the Web of Science Core Collection, a publicly available repository.

Funding

Grants for this study were provided by 10.13039/501100003392 Natural Science Foundation of Fujian Province (2020J011186 , 2021J011315 ); Project of Fujian Provincial Clinical Medical Research Center for First Aid and Rehabilitation in Orthopedic Trauma (2020Y2014 ); 10.13039/100018696 Health Scientific Innovation Platform Program of Fuzhou (2019-S-wp3 ); 10.13039/501100013092 Science and Technology Planning Project of Fuzhou (2022-R-009 ).

CRediT authorship contribution statement

Peisheng Chen: Writing – original draft, Formal analysis, Conceptualization. Bin Chen: Writing – original draft, Formal analysis. Nannan Liu: Investigation, Data curation. Xiaofeng Lin: Software, Methodology. Xiaojuan Wei: Investigation. Bin Yu: Writing – review & editing. Xing Teng: Writing – review & editing, Supervision, Project administration. Fengfei Lin: Writing – review & editing, Supervision, Project administration, Funding acquisition.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

Special thanks to all the researchers who have made valuable contributions to this field.
==== Refs
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