Clinical and research applications of synthetic bone substitutes in equine veterinary medicine: A systematic review

Abstract

Background

Bone grafting in equine medicine offers a promising contribution to treating orthopaedic developmental diseases and chondral, osteochondral and segmental bone defects. Among grafts, synthetic bone substitutes—alloplastics—show favourable biological properties addressing numerous limitations presented by autografts, xenografts and allografts.

Objectives

To compile and disseminate clinical data and research findings from existing publications on the use of alloplastics in horses.

Study Design

Systematic review.

Methods

Following Preferred Reporting Items for Systematic Reviews and Meta‐analysis 2020 guidelines, literature searches were conducted in PUBMED, Scopus and Web of Knowledge. The inclusion criteria covered case reports and research articles on the use of alloplastics in the horses. The selected research articles were grouped considering clinical and experimental studies. A risk of bias assessment was performed for the research articles.

Results

Use of synthetic bone substitutes in horses has been described in 17 publications to date, grouped as 5 case reports and 12 research articles. The latter were subdivided by main study issue—as involved subchondral cystic lesion, aneurysmal bone cyst and chondral, osteochondral or segmental bone defects. The four treatment models were distinguished and described.

Main Limitations

The lack of clinical and alloplastics data in some records. Clinical evaluation in some studies was inconsistent or incomplete. A risk of bias particularly arises from missing data, outcome measurement and the reported results.

Conclusions

In equine medicine, hydroxyapatite, calcium phosphate and β‐tricalcium phosphate were the leading alloplastics applied. When applied alone, they demonstrated osteoconductive and osteoinductive properties, while the addition of biologically active additives—especially autologous bone marrow—enhanced these biological properties toward osteogenic and chondrogenic effects. Treatment outcomes were generally favourable, although segmental bone defect treatment requires considering the limitations associated with weight‐bearing effects. These findings suggest alloplastics in horses may be particularly beneficial for treating certain bone diseases.

1. INTRODUCTION

In recent years, the field of bone grafting in equine medicine has been extensively studied and developed, as it offers a promising contribution to the treatment of orthopaedic developmental diseases, ¹ , ² , ³ , ⁴ , ⁵ , ⁶ chondral defects, ⁷ , ⁸ osteochondral defects ⁸ , ⁹ , ¹⁰ and segmental bone defects. ¹¹ , ¹² , ¹³ , ¹⁴ Bone grafts in equine medicine are used to stimulate or enhance bone healing in clinical cases such as osteochondritis dissecans (OCD), ² , ³ subchondral cystic lesion (SCL) ¹ , ⁴ , ⁵ , ⁶ and aneurysmal bone cyst (ABC). ¹⁵ , ¹⁶ In experimental models, bone grafts help fill cartilage ⁷ , ⁸ , ⁹ , ¹⁰ and bone defects, ⁸ , ⁹ , ¹⁰ , ¹¹ , ¹² , ¹³ , ¹⁴ promote new bone growth ⁷ , ⁸ , ⁹ , ¹⁰ , ¹¹ , ¹² , ¹³ , ¹⁴ and restore structural integrity of bone. ¹¹ , ¹³ , ¹⁴ The use of bone grafts in the treatment of bone diseases and bone defects in horses is a continuously evolving area of veterinary medicine starting from the use of autografts. ¹⁷ Over the years, numerous advancements have been made in the materials and techniques employed in such treatment including xenografts, ¹⁸ , ¹⁹ allografts ²⁰ , ²¹ and alloplastics. ¹⁴ , ¹⁶

Autografts represent bone grafts harvested from the same individual. ¹⁷ Their main advantage lies in the presence of living bone cells, growth factors and the natural scaffold, which promote new bone formation, thus providing osteogenic, osteoinductive and osteoconductive effects, respectively. ²² , ²³ However, the application of autografts requires harvesting tissue from an additional surgical site, which increases the risk of complications and prolongs the duration of surgery. ²⁴ Additionally, the amount of bone that can be harvested from single site is limited, and in some cases not meeting the required volume of defect that needs grafting. ²⁵ Another option includes implantation of xenografts which represent bone grafts derived from individuals from different species (e.g., cattle). However, their application in equine veterinary medicine is limited due to the risk of severe immune reactions and graft rejection. ¹⁸ , ¹⁹ An alternative includes implantation of allografts which represent bone grafts obtained from other individuals of the same species. This option eliminates the need for additional surgical intervention in the recipient; however, carries the risk of an undesirable immune response. ²⁶ To address these limitations, numerous studies have been conducted on the use of alloplastics, which represent synthetic bone substitutes. ⁷ , ⁸ , ⁹ , ¹⁰ , ¹¹ , ¹² , ¹³ , ¹⁴

The considerable research interest in synthetic bone substitutes is driven by their potential to provide alternatives to natural grafts, reducing the risk of surgical complications and post‐surgical immune rejection, while also making these procedures more accessible and easier to implement. ²⁷ Therefore, an ideal alloplastic material is expected to possess favourable biological properties, including osteoconductive, osteoinductive, osteogenic and chondrogenic characteristics. Osteoconduction refers to the capacity of a graft to support natural bone formation by providing a structural surface upon which osteoblasts can migrate and into which blood vessels can grow. ²⁸ , ²⁹ Osteoinduction is the process by which osteogenesis is stimulated through the activation of mesenchymal and osteoprogenitor cells in the host tissue, leading to their differentiation into osteoblasts and the subsequent formation of new bone. ²⁸ , ²⁹ The osteogenic property of a graft reflects its intrinsic ability to generate new bone regardless of the presence of host osteoprogenitor cells. ²⁹ , ³⁰ Similarly, the chondrogenic property denotes the graft's capacity to form new cartilage independent of the host's chondroprogenitor cells. ³¹ Moreover, from a practical point of view, an ideal alloplastic should be easy to produce, store and apply. ²⁷

Given the recent increase in clinical interest in the use of synthetic bone substitutes in equine practice, ¹ , ² , ³ , ⁴ , ⁵ , ⁶ , ¹⁵ , ¹⁶ , ³² particularly for the treatment of bone diseases, ¹ , ² , ³ , ⁴ , ⁵ , ⁶ , ¹⁵ , ¹⁶ a systematic review of the clinical applications, procedures performed and outcomes obtained from the use of alloplastics in equine medicine—including their types, formulations and biological properties—would greatly benefit both equine practitioners and researchers. Therefore, the aim of this systematic review is to compile and organise clinical data and research findings from existing publications on alloplastic‐based treatment strategies in equine medicine. Following the PICOT (Population, Intervention, Comparison, Outcome, Time) format, the research question is formulated as: ‘In horses with bone diseases and defects excluding cadavers (P), what synthetic bone substitutes (I), compared to untreated controls/standard treatment procedures (C), have been applied and described as clinically effective and/or biologically favourable (O) in existing publications (T)’.

2. METHODS

2.1. Eligibility criteria

The inclusion criterion for this systematic review encompassed case reports and research articles on synthetic bone substitutes used in equines from 1968 to March 2025.

2.2. Exclusion criteria

Articles without full‐text availability in English or lacking an available abstract were excluded. Records related to equine stem cell cultures, autografts, allografts, xenografts, nonresorbable grafts and cadaver studies on alloplastics were excluded during the selection process.

2.3. Search strategies

Literature searches were conducted in March 2025 using the following electronic search databases; PUBMED (search date: 7 March 2025; search strategy: #1: horse*[tw] OR equine*[tw], #2: bone graft*[tw] OR hydroxyapatite*[tw], #3: #1 AND #2; retrieved records: 241), Scopus (search date: 7 March 2025; search strategy: TITLE‐ABS‐KEY [horse OR equine] AND [‘bone graft’ OR hydroxyapatite]; retrieved records: 664), Web of Knowledge (search date: 7 March 2025; search strategy: #1: TS = [horse* OR equine*], #2: TS = [‘bone graft*’ OR hydroxyapatite*], #3: #1 AND #2; retrieved records: 620). No additional filters and limits were used. Detailed search strategies are available in Text S1.

2.4. Selection process

The selection process was performed following the Preferred Reporting Items for Systematic Reviews and Meta‐analysis (PRISMA) guidelines. ³³ Records were compiled into an Excel file and duplicates were removed manually. An unblinded records selection included title screening, abstract screening and full text screening. The selection process was conducted by two independent reviewers (first author and last author). Any disagreements were resolved by a third party (second author). No automation tools were used. In the title screening step, titles referring to species other than horses and items other than bone grafts were excluded. If species or items could not be determined, the records were proceeded to the next step. In the abstract screening step, abstracts unrelated to horses or bone grafts were excluded. If species or graft type were not specified, the records were proceeded to the next step. Records that survived the selection process underwent full‐text retrieval. At this stage, records were divided into studies on equine stem cells and studies on horses. Records related only to equine stem cell cultures were excluded and summarised in Table S1. Studies on horses were divided into studies on autografts, allografts, xenografts, nonresorbable grafts and alloplastics. Records related to horses and bone autografts were summarised in Table S2, horses and bone allografts in Table S3, horses and xenografts in Table S4, horses and nonresorbable grafts in Table S5, as well as horses and alloplastics in Table S6. Finally, records related to horses and alloplastics were divided into studies on cadaver horses and studies on living horses. At this stage, studies on cadaver horses were excluded; thus, the data collection process included only studies on alloplastics conducted on living horses. Details of the selection process are available in Table S7.

2.5. Data collection process

A data extraction sheet was designed based on the Cochrane Consumers and Communication Review Group template. ³⁴ The data extraction sheet is available in Data S1. The data collection process was conducted by two reviewers (first author, who manually extracted data from each record; and last author, who manually reviewed data extraction). Any disagreements were resolved by a third party (second author). No automation tools were used. The extracted information included: the year of publication, the aim of study, the study type, the scope of Primary Research Question (PRQ), ³⁵ the level of Evidence‐Based Medicine Rating (EBMR) in the hierarchy of evidence (if applicable), ³⁵ , ³⁶ demographic data of horses, main clinical or experimental issue, main diagnostic and/or therapeutic procedure, alloplastic characteristic, therapeutic outcome, funding source and ethical approval.

2.5.1. Record grouping process

Records related to living horses and synthetic bone substitutes (alloplastics) were manually grouped based on the study type—as case reports, research articles (randomised controlled trials, prospective cohort studies, retrospective cohort studies, case–control studies, case series and mechanism‐based reasoning included in the EBMR hierarchy of evidence) and other (reviews, commentary or book chapters). Articles other than clinical cases and research articles were excluded from the final evaluation. All case reports and research articles concerning the use of synthetic bone substitutes in living horses were included in the final analysis. Case reports were described as a separate group without additional divisions. Research articles were subsequently subgrouped based on the main study design—as clinical or experimental—and based on the main study issue—as involved SCL, ABC, chondral and osteochondral defects or segmental bone defects. Data grouping process was conducted by two reviewers (first author, who manually grouped records; and last author, who manually reviewed grouping). Any disagreements were resolved by a third party (second author). No automation tools were used. No additional methods were employed to prepare the data for presentation.

2.5.2. Risk of bias assessment

The risk of bias in research studies was assessed using the Cochrane tool for randomised trials (RoB 2) ³⁷ and the Cochrane tool for ‘Risk Of Bias In Non‐randomized Studies of Interventions (ROBINS‐I)’ for non‐randomised trials and observational studies. ³⁸ The risk of bias was assessed by two independent reviewers (the first and last authors). Any disagreements were resolved by a third party (the second author). The Robvis visualisation tool was used to create a traffic‐light plot. No automation tools were used in this process.

2.5.3. Data synthesis

The risk of bias level was used as a source of heterogeneity. However, due to significant heterogeneity, a meta‐analysis was not feasible. Therefore, data analysis was descriptive, and the results were summarised in tables.

3. RESULTS

3.1. Study selection

A total of 1525 records were retrieved following the search, selection and grouping process, as depicted in Figure 1. The primary reasons for study exclusion were discrepancies with the search parameters, such as content unrelated to bone grafts (a total of 608 records) or horses (a total of 243 records). Of the 99 records concerning equine bone grafts, the most common reason for exclusion, which applied to 53 records, was the use of autografts. Subsequently, 10 records were excluded as related to allografts, 7 records were excluded as using cadavers in alloplastic studies, 6 records were excluded as being performed on equine stem cells, 2 records were excluded as investigating nonresorbable grafts, and only one record was conducted—and thus excluded—on xenografts. Consequently, 20 records met the inclusion criteria for horse studies excluding cadavers on synthetic bone substitutes. These records included 5 case reports, 12 research articles and 3 other records (1 narrative review, ³⁹ 1 commentary ⁴⁰ and 1 book chapter ⁴¹ ). These last 3 records were excluded from the final review; thus, 17 records were considered for further analysis.

FIGURE 1.

PRISMA flow diagram depicting records included and excluded from this review. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta‐analysis.

Each case report described synthetic bone substitutes in a single horse, taking a total of five horses under consideration. The research articles included a total of 645 horses; however, the two most extensive studies ⁴ , ⁵ —conducted on 336 (including only 36 horses treated with alloplastics) ⁴ and 222 (including only 6 horses treated with alloplastics) ⁵ horses—involved retrospective analysis of clinical records in relation to the auction value and athletic ability of treated and control horses, while one study ¹⁰ did not report the number of horses used. Apart from these three studies, a detailed discussion on the use of synthetic bone substitutes in horses is considered in a total of 87 horses.

3.2. Case reports on the use of synthetic bone substitutes in horses

A total of five case reports using synthetic bone substitutes in horses were described and summarised in Table 1. ¹ , ² , ³ , ¹⁵ , ³² All case reports involved treatment of young horses between 4 months ³² and 2 years old. ¹⁵ Four out of five case reports were presented with open growth plates, indicating a high regenerative capacity and strong healing potential.

TABLE 1.

Case reports on using synthetic bone substitutes (alloplastics) in the treatment of bone disease.

Paper	Demographic data	Case type (diagnostic/therapeutic)	Main clinical issue (body region, clinical signs, diagnosis)	Treatment procedure	Alloplastic (type, structure, additives)	Alloplastic biological properties	Outcome monitoring	Outcomes (clinical signs, imaging findings)
Kolvek et al. 1	1‐year‐old Czech‐warmblood filly (1 F)	Therapeutic	Limb region (the proximal phalanx), lameness/SCL	Arthrotomy, surgical arthrodesis, alloplastic placement	Ceramic CP cement, applied alone	No data	Clinical examination, radiography	No lameness (6 weeks), new bone formation (3 months)
Stack et al. 2	15‐month‐old Irish filly (1 F)	Therapeutic	Limb region (the lateral trochlear ridge of the distal femur), lameness, severe joint effusion/OCD	Arthroscopy, debridement and microfracture creation of the subchondral bone, alloplastic placement	Composite HAP tri‐layered scaffold (bone layer: HAP and Col1; intermediate layer: Col1 and HyA; cartilage layer: Col1, Col2 and HyA), combined with autologous bone marrow (delivered from microfracture)	OC, OI, CG	Clinical examination; arthroscopy, radiography, ultrasound, synovial fluid assessment	No lameness (5 months), scaffold covered by immature cartilage (5 months), repair of the subchondral bone (22 months), integrity of the joint surface (22 months)
David et al. 15	2‐year‐old Thoroughbred filly (1 F)	Therapeutic	Head region (the mandible), large firm swelling/ABC, tooth malformations (displacement, distortion, hypoplasia)	Open surgery, ABC debridement, alloplastic placement	Composite HAP sponge‐like structure scaffold (composed of Col1), applied alone	OC, OI	Clinical examination, CT	Oral examination within normal limits (3 months), no masticatory disorders (6 months), bone remodelling (14 months)
Tsuzuki et al. 3	13‐month‐old Thoroughbred filly (1 F)	Therapeutic	Limb region (the medial tibial malleolus), no lameness/joint effusion after exercise/OCD	Arthroscopy, debridement, alloplastic placement	Ceramic β‐TCP a sponge‐like structure scaffold; impregnated with gelatin hydrogel microspheres, PRP, BMP‐2 and MSCs b (cultured b from autologous bone marrow collected from the sternum)	OC, OI, OG, CG	No clinical examination; radiography, arthroscopy, CT, HP (biopsy)	Repair of the subchondral bone (12 weeks), scaffold covered by immature cartilage (16 weeks)
Hu et al. 32	4‐month‐old Trakehner colt (1 M)	Therapeutic	Neck region (the vertebral body of C2‐C3), recumbent foal, ataxia/osteomyelitis	Open surgery, debridement, alloplastic placement	Ceramic β‐TCP c implant (no data on graft structure), combined with autologous blood	No data	Clinical examination; radiography, myelography CT	Improvement in neurological examination (7 months); bone remodelling (45 days), fusion of C2–C3 (60 days)

Abbreviations: ABC, aneurysmal bone cysts; β‐TCP, β‐tricalcium phosphate; BMP‐2, bone morphogenetic protein‐2; C2, second cervical vertebra; C3, third cervical vertebra; CG, chondrogenic; Col1, Type I collagen; Col2, Type II collagen; CP, calcium phosphate; CT, computed tomography; F, female; HAP, hydroxyapatite; HP, histopathology; HyA, hyaluronic acid; M, male; MSCs, mesenchymal stem cells; OC, osteoconductive; OCD, osteochondritis dissecans; OG, osteogenic; OI, osteoinductive; PRP, platelet rich plasma; SCL, subchondral cystic lesions.

^a Pore size in μm.

^b Cultured from autologous bone marrow collected from the sternum.

^c Ultraporous particle.

All case reports described the results of treatment of clinical diseases; among them, three case reports involved the use of synthetic bone substitutes in the limb regions, ¹ , ² , ³ while one case report concerned the head region ¹⁵ and another one the neck region. ³² Within the limb regions, the synthetic bone substitutes were used in the treatment of SCL, also referred to as osseous cyst‐like lesion, in the proximal interphalangeal joint, ¹ as well as OCD in the femoropatellar joint ² and the tarsal joint. ³ These case reports were consistent with early developmental orthopaedic diseases (SCL ¹ or OCD ² , ³ ) with concurrent defects in cartilage and subchondral bone, accompanied by lameness ¹ , ² and joint effusion. ² , ³ The single case report in the head region concerned an ABC in the mandible, ¹⁵ while the case report in the neck region involved osteomyelitis localised between the second and third cervical vertebrae (C2–C3). ³² The mandibular ABC was accompanied by swelling and tooth malformations, ¹⁵ while C2–C3 osteomyelitis was clinically presented with recumbency and ataxia. ³²

All horses were treated surgically using different procedures combined with the application of various synthetic bone substitutes. OCD was addressed using less invasive arthroscopy, ² , ³ while SCL, ¹ ABC ¹⁵ and spinal lesions ³² required open surgical procedures. The leading materials used in these procedures included ceramics ¹ , ³ , ³² and composites. ² , ¹⁵ Among ceramics, calcium phosphate (CP) was used in cement formulation, ¹ and beta‐tricalcium phosphate (β‐TCP) was used as a sponge‐like structure scaffold ³ and an implant with not specified formulation. ³² On the other hand, both composites used were based on hydroxyapatite (HAP) combined with Type I collagen (Col1), Type II collagen (Col2) and hyaluronic acid (HyA) in the form of a tri‐layered scaffold ² or combined with Col1 in the form of a sponge‐like structure scaffold. ¹⁵

In case reports, biological properties were assumed based on the material used. In two case reports—one using CP cement ¹ and one using HAP‐based sponge‐like structure scaffold ¹⁵ —no biologically active additives were combined with alloplastics. In contrast, various biologically active additives were included in the remaining three case reports—one using HAP‐based tri‐layered scaffold ² and two using β‐TCP‐based scaffolds/implants. ³ , ³² In one case, the microfracture was created in the subchondral bone to release the autologous stem cells from the underlying bone marrow. ² In contrast, in two cases, scaffolds/implants were impregnated with autologous blood ³² or mesenchymal stem cells (MSCs)—cultured from autologous bone marrow collected from the sternum—mixed with platelet‐rich plasma (PRP) and bone morphogenetic protein‐2 (BMP‐2). ³ When the HAP‐based sponge‐like structure scaffold was applied alone, osteoconductive and osteoinductive alloplastic properties were reported. ¹⁵ Consequently, when the HAP‐based tri‐layered scaffold ² and β‐TCP‐based sponge‐like structure scaffold ³ were combined with biologically active additives, osteoconductivity, ² , ³ osteoinductivity, ² , ³ osteogenicity ³ and chondrogenic potential ² , ³ were stated. However, the biological properties of applied synthetic bone substitutes have not been described in two cases. ¹ , ³²

Clinical outcomes were reported favourable across all case reports, assessed at various follow‐up intervals ranging from 3 months ¹ to 22 months ² post‐surgery. Clinical improvement was noted in four horses, ¹ , ² , ¹⁵ , ³² while in one case clinical examination data were not available. ³ However, in all cases diagnostic imaging evidenced structural healing of the treated bone. Radiography ¹ , ² , ³ , ³² and computed tomography (CT) ³ , ¹⁵ , ³² confirmed new bone formation, ¹ repair of the subchondral bone, ² , ³ bone remodelling ¹⁵ , ³² and bone fusion, ³² while ultrasound ² and arthroscopy ² , ³ confirmed new cartilage growth ² , ³ and joint surface integration. ²

3.3. Research articles on the use of synthetic bone substitutes in horses

A total of 12 research articles using synthetic bone substitutes in horses were divided into 2 groups: one considering clinical studies ⁴ , ⁵ , ⁶ , ¹⁶ and the other considering experimental studies. ⁷ , ⁸ , ⁹ , ¹⁰ , ¹¹ , ¹² , ¹³ , ¹⁴ Given that all research articles investigated the results of a treatment of clinical diseases or induced defects, the studies were then subdivided regarding the main clinical or experimental issue raised. The clinical studies were subgrouped concerning SCL treatment ⁴ , ⁵ , ⁶ and ABC treatment, ¹⁶ while experimental studies were subgrouped to address the management of chondral and osteochondral defects ⁷ , ⁸ , ⁹ , ¹⁰ and segmental bone defects. ¹¹ , ¹² , ¹³ , ¹⁴ These four treatment models are described in the following subsections.

The clinical studies on SCL involved the treatment of young horses aged between 10 months and 2 years old ⁴ , ⁵ , ⁶ ; however, clinical studies of ABC involved horses of all ages (between 1 and 22 years old). ¹⁶ In contrast, the experimental studies were conducted only on healthy horses without clinical disease aged between the ages of 2 and 17. ⁷ , ⁸ , ⁹ , ¹⁰ , ¹¹ , ¹² , ¹³ , ¹⁴

3.3.1. Clinical models for the treatment of SCL

Clinical studies using the synthetic bone substitutes in SCL treatment involved the limb regions as described and summarised in Table 2. ⁴ , ⁵ , ⁶ SCLs were located in the stifle joint, ⁴ , ⁶ the elbow joint, ⁶ the tarsal joint, ⁵ the carpal joint ⁵ , ⁶ and the interphalangeal joint. ⁵ , ⁶ In one clinical study (a case series involving 38 horses), SCLs were associated with lameness, ⁶ whereas in two other studies, no data on clinical examination were reported. ⁴ , ⁵

TABLE 2.

Research articles on using synthetic bone substitutes (alloplastics) in the treatment of subchondral cystic lesions.

Paper	Demographic data	Study type PRQ/EBMR	Main clinical issue (body region, clinical signs, diagnosis)	Treatment (procedure, control)	Alloplastic (type, structure, additives)	Alloplastic biological properties	Outcome monitoring	Outcomes (clinical signs, imaging findings)
Pérez‐Nogués et al. 4	Treated group: 182 horses (Thoroughbred), 1‐year‐old (119 F, 51 M) a Control group: 154 horses (Thoroughbred), 1‐year‐old (73 F, 79 M) a	Therapeutic/ Level 3 (retrospective cohort study)	Limb region (the medial femoral condyle); no data on clinical signs/SCL	Intralesional injection or arthrotomy or extra‐articular surgery; corticosteroid injection (n = 95) or SCL debridement (n = 31) or screw placement (n = 20) or alloplastic placement (n = 36)	HAP implant (no data on graft structure); no data on application type	No data	No clinical data; performance and auction price tracking	No clinical outcomes follow‐up
Pérez‐Nogués et al. 5	Treated group: 113 horses (Thoroughbred), 1‐year‐old (53 F, 60 M) Control group: 109 horses (Thoroughbred), 1‐year‐old (56 F, 53 M)	Therapeutic/Level 3 (retrospective cohort study)	Limb region (the third metacarpal bone, the third metatarsal bone, the proximal phalanx, the middle phalanx); no data on clinical signs/SCL	Intralesional injection or arthrotomy or extra‐articular surgery; corticosteroid injection (n = 61) or SCL debridement (n = 30) or cortical screw placement (n = 16) or alloplastic placement (n = 6)	HAP implant (no data on graft structure); no data on application type	No data	No clinical data; performance and auction price tracking	No clinical outcomes follow‐up
Ravanetti et al. 6	38 horses (25 Thoroughbred/13 Standardbred), 10‐ to 24‐month‐old (21 F, 17 M)	Therapeutic/Level 4 (case series)	Limb region (the medial femoral condyle, the radius, the fourth carpal bone, the proximal phalanx, the middle phalanx); lameness/SCL	Extra‐articular surgery; SCL debridement, alloplastic placement, pin or screw placement (no control group)	Composite HAP b implant (no data on graft structure); (composed of PLLA); applied alone	OC, OI	Clinical examination; radiography, morphometry	No lameness (120 days) in 36/38 horses (94%), lameness (37 months) in 1/38 horses (3%); repair of the subchondral bone (240 days)

Abbreviations: EBMR, Evidence‐Based Medicine Rating; F, female; HAP, hydroxyapatite; M, male; OC, osteoconductive; OI, osteoinductive; PLLA, poly l‐lactic acid; PRQ, Primary Research Question; SCL, subchondral cystic lesions.

^a Sample size and sex distribution given in the article did not match.

^b Particle size in μm referred to as nanoparticles.

All horses were treated surgically. In one study, extra‐articular SCL debridement was followed by alloplastic and pin or screw placement. ⁶ In contrast, in two studies, using four procedures, only one involved alloplastic placement in the SCL. ⁴ , ⁵ Hence, the sample sizes that were treated with alloplastics in these 2 studies were 36 horses ⁴ and 6 horses, ⁵ respectively. All horses were treated using HAP‐based implants; however, in one study, the implant was characterised in detail, ⁶ while in two studies, no data on alloplastic structure, formulation, biologically active additives and biological properties were provided. ⁴ , ⁵ In this single study, the implant was composed of HAP and poly l‐lactic acid (PLLA). The composite formulation was not described, but the implant appeared as a screw‐like scaffold in the presented arthroscopic images. This HAP‐based implant was applied alone, with no biologically active additives, resulting in a report of osteoconductive and osteoinductive properties of the alloplastic used. ⁶

Similar to the incomplete description of materials and methods, two studies did not provide a detailed or comprehensive follow‐up of clinical outcomes. These studies analysed clinical records related to the auction value and athletic ability of the horses involved, ⁴ , ⁵ with athletic ability representing a brief but acceptable form of clinical outcome reporting. These two studies showed that when comparing four SCL treatment procedures—corticosteroid injection, SCL debridement, screw placement and alloplastic placement—the athletic prognosis was similar. ⁵ However, horses treated with SCL debridement had significantly fewer race starts than those treated with alloplastics. ⁴

In the Ravanetti study, inclusion criteria included a diagnosis of SCL as the cause of lameness, but regional anaesthesia was only done ‘when possible’, ⁶ suggesting that the cause of lameness was not verified in every case. The clinical outcome was reported as favourable, as no lameness was noted in 94% of treated horses just 120 days post‐surgery. The lameness resolved later in one horse, and in one horse, it persisted for even 37 months post‐surgery. In this study, structural healing of the treated bone was evidenced by radiography supported by morphometry, evidencing repair of the subchondral bone just 240 days post‐surgery. ⁶

3.3.2. Clinical model for the treatment of ABC

Clinical study using the synthetic bone substitutes in ABC treatment considered the head region—specifically the mandible—as described in Table 3. ¹⁶ This case series involved four horses. All horses were treated surgically by open surgery, which included ABC debridement and alloplastic placement. Horses were treated using ceramic β‐TCP granules applied alone or combined with biologically active additives—autologous bone marrow collected from the sternum and tuber coxae. Unfortunately, the properties of the alloplastic used have not been reported. However, the clinical outcome was reported as favourable, as no pain, decreased mandibular swelling and reduced lesion size were noted in all treated horses between 6 and 8 months post‐surgery. Reduction of the lesion size was also evidenced radiologically, as radiography and CT revealed the structural healing of the treated bone 24 months post‐surgery. However, in one case, post‐surgery inflammation required removal of residual alloplastic. ¹⁶

TABLE 3.

Research articles on using synthetic bone substitutes (alloplastics) in the treatment of aneurysmal bone cyst.

Paper	Demographic data	Study type PRQ/EBMR	Main clinical issue (body region, clinical signs, diagnosis)	Treatment (procedure, control)	Alloplastic (type, structure, additives)	Alloplastic biological properties	Outcome monitoring	Outcomes (clinical signs, imaging findings)
Spoormakers et al. 16	4 horses (Dutch Warmblood/Icelandic horse /Standardbred /Polo pony), 1‐ to 22‐year‐old (1 F, 3 M)	Therapeutic/Level 4 (case series)	Head region (the mandible); swelling, pain, quidding /ABC	Open surgery; ABC debridement; alloplastic placement (no control group)	Ceramic β‐TCP granules; applied alone or combined with autologous bone marrow (collected from the sternum and tuber coxae)	No data	Clinical examination; radiography, CT	Clinical improvement, no pain (6–8 months); reduction of the lesion size (24 months)

Abbreviations: ABC, aneurysmal bone cysts; β‐TCP, β‐tricalcium phosphate; CT, computed tomography; EBMR, Evidence‐Based Medicine Rating; F, female; M, male; PRQ, Primary Research Question.

3.3.3. Experimental models for the treatment of chondral and osteochondral defects

Experimental studies using the synthetic bone substitutes to treat chondral ⁷ , ⁸ and osteochondral ⁸ , ⁹ , ¹⁰ defects involved the limb regions as described and summarised in Table 4. ⁷ , ⁸ , ⁹ , ¹⁰ Defects were induced surgically in the stifle joint ⁷ , ⁹ and the metacarpophalangeal joint ⁸ during arthroscopy ⁹ or arthrotomy. ⁷ , ⁸ In one study, the defects' anatomical location did not match the main text and the figures presented, and the surgical protocol was not provided. ¹⁰

TABLE 4.

Research articles on using synthetic bone substitutes (alloplastics) in the treatment of chondral and osteochondral defects.

Paper	Demographic data	Study type PRQ/EBMR	Main experimental issue (body region, induced defect)	Treatment (procedure, control)	Alloplastic (type, structure, additives)	Alloplastic biological properties	Outcome monitoring	Outcomes (clinical signs, imaging findings)
Smanik et al. 7	3 horses (mixed breed), 4‐ to 8‐year‐old (3 F)	Therapeutic/Level 1 (randomised controlled trial)	Limb region (the medial trochlear ridge of the femur)/chondral defect	Arthrotomy; microfracture creation of the subchondral bone; subchondral injection of FG or direct injection of FG or subchondral injection of alloplastic with direct injection of FG or control (no injection)	Ceramic CP cement; injected simultaneously with autologous FG	OC	Clinical examination; radiography, post‐mortem: CT, MRI, μCT, gross dissection, HP	Lameness, reduction of joint motion, joint effusion; euthanasia (2 weeks); widening of the microfracture holes, new cartilage growth, new bone formation (no difference in HP between alloplastic and control)
McCarrel et al. 9	12 horses (no breed data), 2‐ to 5‐year‐old (no data on sex distribution)	Therapeutic/Level 1 (randomised controlled trial)	Limb region (the lateral trochlear ridge of the femur)/osteochondral defect	Arthroscopy, alloplastic placement or control (microfracture creation of the subchondral bone)	Composite β‐TCP bi‐phasic scaffold (bone phase: β‐TCP and PLA; cartilage phase: Col1); combined with autologous bone marrow (collected from the sternum)	OC, OI, OG	No clinical examination; radiography, arthroscopy, post‐mortem: MRI, gross dissection, HP, mechanical tests	New cartilage growth (4 months), new bone formation (12 months), euthanasia (24 months); (no difference in HP between alloplastic and positive control)
Kon et al. 8	2 horses (Standardbred), 6‐ to 7‐year‐old (2 M)	Therapeutic/Level 2 (prospective cohort study)	Limb region (the third metacarpal bone)/chondral defect, osteochondral defect	Arthrotomy; defect debridement; alloplastic placement or control (unfilled defect)	Composite HAP a bi‐ and tri‐layered scaffold (bone layer: Mg‐HAP; intermediate layer: HAP and Col1; cartilage layer: Col1); combined with autologous blood (delivered from defect debridement)	OC, OI	Clinical examination b ; arthroscopy, post‐mortem: gross dissection, HP	Lameness, swelling (15 days); new cartilage growth (2 months), euthanasia (6 months); new bone formation (no difference in HP between chondral and osteochondral defects, no control)
Tampieri et al. 10	No data	Therapeutic/Level 2 (prospective cohort study)	Limb region (the knee joint or the metacarpophalangeal joint or the metatarsophalangeal joint c ) /osteochondral defect	No data	Composite HAP a tri‐layered scaffold (bone layer: HAP and Col; intermediate layer: HAP and Col; cartilage layer: Col and HyA); applied alone	No data	No clinical examination; post‐mortem: HP, microscopic assessment	Euthanasia (3 months); new cartilage growth, new bone formation (no data on control)

Abbreviations: β‐TCP, β‐tricalcium phosphate; Col, collagen; Col1, Type I collagen; CP, calcium phosphate; CT, computed tomography; EBMR, Evidence‐Based Medicine Rating; F, female; FG, fibrin glue; HAP, hydroxyapatite; HP, histopathology; HyA, hyaluronic acid; M, male; μCT, microcomputed tomography; Mg‐HAP, magnesium hydroxyapatite; MRI, magnetic resonance imaging; OC, osteoconductive; OG, osteogenic; OI, osteoinductive; PLA, polylactic acid; PRQ, Primary Research Question.

^a Referred to as nanoparticles/nanocrystals.

^b Inconsistent data on clinical examination (lack of description of the examination in materials and methods section).

^c The main text (knee joint) and the figures (the metacarpophalangeal joint/the metatarsophalangeal joint) in the article did not match.

The leading materials used in these procedures included composites based on HAP ⁸ , ¹⁰ or β‐TCP. ⁹ In one study, HAP was combined with magnesium ions and Col1 in the form of a bi‐ or tri‐layered scaffold. ⁸ In the second study, HAP was mixed with Col (with no specified type) and HyA in the form of a tri‐layered scaffold. ¹⁰ In the third study, β‐TCP was blended with Col1 and polylactic acid (PLA) in the form of a bi‐phasic (bi‐layered) scaffold. ⁹ Only one model of chondral defect was treated using ceramic CP cement injected simultaneously with autologous fibrin glue (FG). In this research, FG injection was also tested without alloplastics. ⁷ As there were no other biologically active additives, only the osteoconductive properties of the material used were considered. ⁷ In the model utilising HAP‐based multi‐layered scaffold combined with autologous blood delivered from defect debridement, osteoconductivity and osteoinductivity were reported. ⁸ In the model using β‐TCP‐based bi‐phasic scaffold combined with autologous bone marrow collected from the sternum, osteoconductivity, osteoinductivity and osteogenicity were stated. ⁹ The biological properties of the applied alloplastic have not been described in the model using the HAP‐based tri‐layered scaffold alone. ¹⁰ This study also suffers from a lack of demographic and clinical data, making further comparisons difficult. ¹⁰

Treatment outcomes were favourable across all models, although the clinical examination was described only in one study. ⁷ In another study, clinical data were inconsistently described. ⁸ In the other two studies, no clinical examination was reported. ⁹ , ¹⁰

Clinically assessed horses were lame after chondral ⁷ , ⁸ and osteochondral defects ⁸ induction, which improved over time. ⁷ , ⁸ Horses were also monitored radiographically ⁷ , ⁹ and/or arthroscopically ⁸ , ⁹ and then euthanised at various intervals ranging from 2 weeks ⁷ to 24 months ⁹ post‐surgery. Structural healing of the treated cartilage and bone was confirmed post mortem by new cartilage growth ⁷ , ⁸ , ⁹ , ¹⁰ and new bone formation with histological evaluation. ⁷ , ⁸ , ⁹ , ¹⁰ Interestingly, the new growing tissues did not differ histopathologically between the alloplastic‐treated and the control groups. ⁷ , ⁸ McCarrel's study ⁹ used a positive control, comparing the cartilage repair device with microfracture results. The histological findings did not show that the repair tissue in the alloplastic‐treated group was superior to that in the positive control groups. However, in Smanik's study, ⁷ which included an untreated negative control, no significant histological differences were observed between the treated and control groups. Nonetheless, certain limitations—such as the short study period in this research—may have influenced these findings.

3.3.4. Experimental models for the treatment of segmental bone defects

Experimental studies using the synthetic bone substitutes to treat segmental bone defects involved the limb regions as described and summarised in Table 5. ¹¹ , ¹² , ¹³ , ¹⁴ Defects were induced surgically in the third ¹² and fourth ¹¹ metacarpal bones as well as the second and fourth metatarsal bones ¹³ , ¹⁴ using ostectomy ¹¹ , ¹² , ¹³ , ¹⁴ or osteotomy. ¹³

TABLE 5.

Research articles on using synthetic bone substitutes (alloplastics) in the treatment of segmental bone defects.

Paper	Demographic data	Study type PRQ/EBMR	Main experimental issue (body region, induced defect)	Treatment (procedure, control)	Alloplastic (type, structure, additives)	Alloplastic biological properties	Outcome monitoring	Outcomes (clinical signs, imaging findings)
Grzeskowiak et al. 11	5 horses (Thoroughbred/Quarter Horse/Rocky Mountain/Standardbred/mixed breed), 4‐ to 10‐year‐old (5 F)	Therapeutic/Level 1 (randomised controlled trial)	Limb region (the fourth metacarpal bone)/segmental bone defect	Ostectomy, alloplastic placement or control (unfilled defect)	Composite HAP block scaffold (composed of PU and DBP); applied alone	OC, OI	No clinical examination; thermography, ultrasound, radiography, CT, HP (biopsy)	No pain, no lameness a ; new cartilage growth, new bone formation (60 days) (more with alloplastic than control)
Nóbrega et al., 2017 12	6 horses (crossbreed), 6‐ to 8‐year‐old (6 F)	Therapeutic/Level 2 (prospective cohort study)	Limb region (the third metacarpal bone)/segmental bone defect	Ostectomy; alloplastic placement or control (unfilled defect)	Composite CC implant (no data on graft structure) (composed of PU); applied alone	OC	No clinical examination; HP (biopsy)	New bone formation (less with alloplastic than control) (120 days)
Perrier et al. 13	9 horses (no breed data), 3‐ to 8‐year‐old (no data on sex distribution)	Therapeutic/Level 1 (randomised controlled trial)	Limb region (the second metatarsal bone, the fourth metatarsal bone)/segmental bone defect	Ostectomy and osteotomy; alloplastic placement or autologous CBG or control (unfilled defect)	Ceramic CP cement; combined with rhBMP‐2	OC, OI	Clinical examination b ; radiography, post‐mortem: HP, mechanical tests	No lameness, swelling (2 weeks); new bone formation (10 weeks); euthanasia (12 weeks); new bone formation (more with alloplastic than control)
Waselau et al. 14	8 horses (various breeds), 6‐ to 17‐year‐old (8 F)	Therapeutic/Level 2 (prospective cohort study)	Limb region (the second metatarsal bone, the fourth metatarsal bone)/segmental bone defect	Osteotomy; alloplastic placement or control (unfilled defect)	Composite CP cement (composed of Mg and saccharose) or ceramic CP cement; applied alone	No data	Clinical examination; radiography, post‐mortem: CT, mechanical tests, HP	No lameness, no swelling, no drainage; new bone formation and remodelling (4 weeks); euthanasia (7 weeks); new bone formation (more with Mg‐CP than CP or control)

Abbreviations: CBG, cancellous bone graft; CC, calcium carbonate; CP, calcium phosphate; CT, computed tomography; DBP, decellularised bone particles; EBMR, Evidence‐Based Medicine Rating; F, female; HAP, hydroxyapatite; HP, histopathology; Mg, magnesium oxide; OC, osteoconductive; OI, osteoinductive; PRQ, Primary Research Question; PU, polyurethane; rhBMP‐2, recombinant human bone morphogenetic protein‐2.

^a Declared in the discussion section, not reported in the results section.

^b Inconsistent data on clinical examination (lack of description of the examination in materials and methods section).

The leading materials used in these procedures included composites based on HAP, ¹¹ calcium carbonate (CC) ¹² or CP. ¹⁴ In one study, HAP was combined with polyurethane (PU) and decellularised bone particles (DBP) and used in the form of a block scaffold. ¹¹ In the second study, CC was combined with PU; however, the implant formulation has not been detailed. ¹³ In the third study, CP cement was combined with magnesium oxide and saccharose in two quantitative proportions. ¹⁴ Only one model of segmental bone defect was treated using ceramic CP cement combined with recombinant human bone morphogenetic protein‐2 (rhBMP‐2). ¹⁴ In this model, osteoconductivity and osteoinductivity were reported. ¹⁴ In all other models, ¹¹ , ¹² , ¹⁴ the application of composites alone resulted in the evidence of the osteoconductive ¹¹ , ¹² and osteoinductive ¹¹ properties of the alloplastic used. In one model, the biological properties of the applied alloplastic have not been described. ¹⁴

Treatment outcomes were predominantly favourable across all models, although the clinical examination was reported only in one study. ¹⁴ In the other two studies, a favourable clinical outcome was declared only in the results ¹³ or discussion ¹¹ sections. In another study, no clinical examination was reported. ¹² Clinically assessed horses were not lame after defect induction ¹¹ , ¹³ , ¹⁴ and local swelling was confirmed in one study. ¹³ Horses were also monitored radiographically ¹¹ , ¹³ , ¹⁴ and with CT ¹¹ for bone healing as well as ultrasonographically ¹¹ and/or thermographically ¹¹ for post‐surgery wound assessment. Two studies were terminated by euthanasia at various intervals ranging from 7 ¹⁴ to 12 weeks ¹³ post‐surgery and then the histopathology (HP) samples were collected. Two other studies were finished without euthanising horses; however, HP samples were also collected by biopsy at various intervals ranging from 60 ¹¹ to 120 days ¹² post‐surgery. Structural healing of the treated bone was confirmed with HP by new bone formation ¹¹ , ¹² , ¹³ , ¹⁴ and bone remodelling. ¹⁴ However, the higher growth of new bone was reported histopathologically predominantly when composite HAP block scaffold, ceramic CP cement, composite CP cement alloplastics were used than in the control. ¹¹ , ¹³ , ¹⁴ In contrast, in one study, less growth of new bone was reported when composite CC alloplastics were used than in the control. ¹²

3.4. The risks of bias in research studies

The risks of bias in individual research articles are depicted in the traffic‐light plot presented in Figure 2. The randomised trials ⁷ , ⁹ , ¹¹ , ¹³ show low risk of bias arising from the randomisation process, deviations from intended interventions and missing outcome data; except for one study on segmental bone defect, which has inconsistent data on clinical examination. Some clinical data were described in the results section; however, their assessment was not described in the materials and methods section. ¹³ All randomised trials ⁷ , ⁹ , ¹¹ , ¹³ show at least some concerns in measuring the outcome and selection of the reported results; as timepoints in which individual clinical signs and both imaging and HP findings are described are difficult to determine, and some results are simply missing. However, the biggest problem causing a high risk of bias in measuring the outcome is the lack of clinical examination. ⁹ , ¹¹

FIGURE 2.

Traffic‐light plot of risk of bias in research studies representing (A) randomised trials and (B) non‐randomised trials or observational studies of interventions regarding the treatment of horses using alloplastics.

Among non‐randomised trials or observational studies, ⁴ , ⁵ , ⁶ , ⁸ , ¹⁰ , ¹² , ¹⁴ , ¹⁶ almost all research showed low risk of bias in classifying interventions and deviation from intended interventions; while one study ¹⁰ induced moderate to critical doubts in all assessed domains. In this study, ¹⁰ no demographic data were provided, the body region declared in the main text (knee joint) did not match with the body region presented on figures (the metacarpophalangeal joint or the metatarsophalangeal joint), treatment protocol was not provided, part of the alloplastic characteristic was missing, and the outcome was not clinically monitored as both clinical examination and diagnostic imaging were missing. ¹⁰ In two studies, ⁶ , ¹⁶ a moderate risk of bias due to confounding and a moderate risk of bias due to participant selection arose from the case series study type, as this type of study could not be assessed as comparable to a well‐performed randomised trial. While in the other two studies, ⁴ , ⁵ a moderate risk of bias due to confounding and participant selection arose from the study's retrospective nature, where important data were generalised or omitted. In these two studies, ⁴ , ⁵ the alloplastic characteristic and clinical monitoring of treatment outcome were missing, making them overly judged as being at critical risk of bias. One study was overly judged as critical ¹² due to the missing data on the alloplastic characteristic; however, this study also lacked outcome monitoring via clinical examination and diagnostic imaging. One other study ⁸ suffered from the lack of a clinical examination in the materials and methods section; however, some clinical signs and arthroscopic assessment of the defective joint were presented. Thus, in this group, only two studies ⁶ , ¹⁶ showed low to moderate risk of bias across all domains, representing a well‐described case series.

4. DISCUSSION

Despite significant advances in tissue engineering and biomaterials, no single, universally accepted optimal synthetic bone substitute exists. ⁴² This is due to the inability to combine, within a single material, all favourable biological properties: the biological activity and absence of immune reactions of autografts ²² , ²³ ; the unlimited availability of xenografts, ¹⁸ , ¹⁹ allografts ²³ and alloplastics ¹ , ² , ³ , ⁴ , ⁵ , ⁶ , ⁷ , ⁸ , ⁹ , ¹⁰ , ¹¹ , ¹² , ¹³ , ¹⁴ , ¹⁵ , ¹⁶ ; and controlled degradation ⁴² adjusted to equine clinical requirements. ¹ , ² , ³ , ⁴ , ⁵ , ⁶ , ¹⁵ , ¹⁶ , ³² Therefore, this systematic review summarises the clinical applications, procedures and outcomes associated with the use of alloplastics in equine medicine, aiming to systematise their characteristics and highlight the resulting benefits for equine practitioners and researchers.

4.1. Effect of alloplastic properties on their clinical applications

In biomaterials nomenclature, four main categories of materials are distinguished: ceramics, composites, polymers and metals. ⁴³ In equine medicine, composites and ceramics are predominately used; among them, HAP, CP and β‐TCP are the leading alloplastics applied clinically ¹ , ² , ³ , ⁴ , ⁵ , ⁶ , ¹⁵ , ¹⁶ , ³² and experimentally. ⁷ , ⁸ , ⁹ , ¹⁰ , ¹¹ , ¹² , ¹³ , ¹⁴ These alloplastics continue to be the most extensively studied owing to their compositional resemblance to the native mineral phase of bone, namely HAP (Ca₁₀[PO₄]₆[OH]₂), CP (CaP) and β‐TCP (β‐Ca₃[PO₄]₂). ⁴⁴

In the reviewed studies, HAP was used in the form of microsize ⁶ and nanosize ⁸ , ¹⁰ particles. Unfortunately, in many studies, the particle size was not reported, ² , ⁴ , ⁵ , ¹¹ , ¹⁵ even though the biological properties of HAP vary significantly across different formulations and are strongly influenced by grain size and specific surface area. It is worth noting that HAP particle size markedly affects the kinetics and efficiency of water adsorption, which is related to its specific surface area; as that particle size decreases, osteoinductivity increases. ⁴⁵ , ⁴⁶

Another way to enhance the biological, chemical or mechanical properties of HAP is by incorporating specific ions into the ceramic crystal lattice to create composites. ⁴⁷ In equine studies, HAP doped with Mg ions was used to treat chondral and osteochondral defects, aiming to increase the physicochemical, structural and morphological compatibility of the composite with new bone formation. ⁸ In addition to enhancing osteoconductivity, Mg ions confer a density and elasticity to the newly formed tissue that are comparable to those of native bone. Therefore, incorporating Mg into HAP may be pivotal for improving bone healing, ⁴⁸ although this effect has not yet been studied in equine specimens by comparing Mg‐doped and non‐doped HAP grafts in one study. On the other hand, CP doped with Mg and saccharose was used to treat segmental bone defects in horses, resulting in greater fragment anchorage, enhanced bone healing and superior osteogenesis compared with non‐doped CP cement and unfilled defect. ¹⁴

CP cements are formulated as a powder‐liquid system that sets in place upon mixing, typically forming HAP or a combination of unreacted and secondary phases. Because they harden in place, CP cements provide a practical solution for irregular or hard‐to‐reach bone defects, particularly in minimally invasive procedures. ⁴⁹ Consequently, CP cements have been applied clinically for filling SCL, ¹ experimentally induced chondral defect, ⁷ and experimentally induced segmental bone defects. ¹³ , ¹⁴

Finally, β‐TCP is one of the most widely used synthetic bone substitutes in human medicine ⁴⁴ ; however, in equine medicine, its application is less common, giving way to HAP and CP. β‐TCP exhibits not only osteoconductive but also osteoinductive and osteogenic properties, promoting complete bone defect regeneration by stimulating bone‐like cell resorption. ⁴⁴ The responses of bone‐like cells are closely related to the porosity of β‐TCP, as high porosity levels—ranging from 60% to 90%—influence the particle surface area available for cellular interaction, ⁵⁰ which is critical for nutrient exchange and cell migration. ⁵¹ β‐TCP scaffolds typically exhibit pore diameters ranging from <10 μm for micropores to 100–500 μm for macropores. ⁵¹ In the reviewed studies, the use of β‐TCP scaffolds was described in two studies—including sponge‐like structure scaffold ³ and bi‐phasic (bi‐layered) scaffold, ⁹ although porosity was reported only for sponge‐like structure scaffold. ³ Overall, β‐TCP porosity was described in two studies as microporous ³ and ultraporous, ³² while in two other studies it was not reported. ⁹ , ¹⁶ The ultraporous form was found to better mimic the architecture of native bone and to more effectively promote bone ingrowth and vascularisation. ⁵² Despite ongoing research, the physicochemical characteristics of β‐TCP—including its crystallographic structure—remain incompletely understood. ⁴⁴ Consequently, its clinical outcomes, both in humans ⁴⁴ and horses, ¹⁶ may be somewhat unpredictable. This was likely exemplified in one case involving ABC treatment, in which residual ceramic β‐TCP granules required removal ¹⁶ probably due to post‐surgical immune‐based graft rejection. ²⁷

One may observe, in the given studies, ⁶ , ⁹ that polymer/ceramic implants were composed of various forms of PLA biodegradable polymer. PLA exists in two mirror‐forms, called l‐ and d‐lactic acid resulting in: PLLA, poly‐d‐lactic acid and poly‐d,l‐lactic acid. They all share typical features—good biocompatibility, biodegradability and stimulation of biological activity. However, they differ in melting temperature, tensile strength and degradation time. These features predefine their future application in bone, cartilage or soft tissues matching their specific rate of regeneration. McCarrel et al. ⁹ described application of bi‐layered scaffolds composed of PLA and β‐TCP for the osteochondral defect regeneration, while Ravanetti et al. ⁶ reported application of the screw implants for subchondral cysts composed of PLLA blended with HAP. Consequently, these two polymers differed in their dissolution times within tissues: PLLA requires approximately 8–12 months for complete absorption, whereas PLA takes up to 48 months. ⁵³ In the case of the PLA composite, horses were euthanised after 24 months, at which time there was no radiographic difference between PLA and positive control group. ⁹ For PLLA composite, one horse was monitored for 37 months, after which the radiolucency representing the original screw‐like shape implant was not visible on the radiographs. ⁶ In both cases, PLLA and PLA were providing biomechanical support and a three‐dimensional structure and ultimately degrading into natural body metabolites. ⁵⁴ However, radiological assessment of these implant absorptions demonstrated limited value, as PLA and PLLA are radiolucent; therefore, their absorption rate assessment based solely on radiographic appearance is debatable.

4.2. Effect of biological active additives on the alloplastic properties

Synthetic bone substitutes hold great potential in bone regeneration, as they exhibit favourable biological properties. When applied alone, HAP composites ⁶ , ¹¹ , ¹⁵ and CC composites ¹² have demonstrated osteoconductive ⁶ , ¹¹ , ¹² , ¹⁵ and osteoinductive ⁶ , ¹¹ , ¹⁵ properties by providing a structural surface that supports osteoblast migration and vascular ingrowth, ²⁸ , ²⁹ as well as by stimulating the activation of mesenchymal and osteoprogenitor cells in host tissue. ²⁸ , ²⁹ However, the incorporation of biologically active additives has been shown to further enhance the biological properties of HAP composites, ² β‐TCP composites ⁹ and β‐TCP ceramics, ³ endowing them with osteogenic ² , ³ , ⁹ and, in some cases, chondrogenic ³ properties by promoting new tissue formation that can occur independently of host osteoprogenitor ²⁹ , ³⁰ or chondroprogenitor cells. ³¹

In equine studies, several biologically active additives have been used to enhance the regenerative capacity of alloplastics, including: autologous blood, ⁸ , ³² autologous bone marrow ² , ⁹ , ¹⁶ and MSCs cultured from autologous bone marrow and combined with PRP and BMP‐2. ³ While also osteogenic ² , ³ , ⁹ and/or chondrogenic ³ effects were observed following the addition of bone marrow or MSCs, only osteoconductive and osteoinductive properties were reported when autologous blood was used. ⁸ , ³² Interestingly, supplementation with rhBMP‐2 alone, ¹³ without the combination of MSCs, PRP and BMP‐2, ³ did not extend the biological properties of alloplastics to include osteogenicity. This suggests that neither blood nor growth factors alone can supply the osteoprogenitor or chondroprogenitor cells necessary to promote and support new bone formation or new cartilage growth independent of host cells. ²⁹ , ³⁰ , ³¹ Therefore, the addition of bone marrow to synthetic bone substitutes—as a source of biologically active additives—is particularly beneficial in equine medicine. Consequently, autologous bone marrow is the most commonly used additive, which may be derived from the sternum, ³ , ⁹ , ¹⁶ from the tuber coxae ¹⁶ or from microfractures intentionally created in the subchondral bone at the site of alloplastic placement. ²

4.3. Benefits of using alloplastic in OCD treatment

In OCD, one of the main challenges lies in the need to regenerate both the articular cartilage and the underlying subchondral bone. Conventional techniques such as debridement, ⁸ drilling ⁷ and microfracture creation ⁷ , ⁹ primarily target cartilage repair by relying on MSCs migration from bone marrow. However, the microfracture creation technique is currently discouraged due to its association with SCL formation. ⁵⁵ Furthermore, the conventional approaches often lead to the formation of fibrocartilage, which lacks the biomechanical strength and viscoelastic properties of native hyaline cartilage, ⁸ , ⁹ In cases with large lesions extending into the subchondral bone, the treatment becomes even more complex, as it involves the regeneration of two distinct tissues with different healing capacities. ⁸ , ⁹ Consequently, several authors have emphasised the need for bi‐ ⁸ , ⁹ and tri‐layered ² , ⁸ , ¹⁰ scaffolds designed to meet the biological and functional requirements necessary to guide the simultaneous regeneration of bone and hyaline cartilage in large OCD lesions. For example, in a case report on OCD treatment, Tsuzuki et al. ³ demonstrated that the use of an impregnated, sponge‐like structure scaffold (designed as a bilayer) promoted tissue regeneration within the lesion. However, the newly formed tissue was identified as fibrocartilage, underscoring the persistent challenge of achieving true hyaline cartilage repair in vivo. Concluding, in the context of osteochondral tissue engineering, experimental models for the treatment of chondral and osteochondral defects are employed to develop optimal bi‐ or tri‐layered scaffolds. ⁷ , ⁸ , ⁹ , ¹⁰ These approaches aim to simultaneously recreate both cartilage and bone within a single construct using three‐dimensional porous biomaterials seeded with host cells. ⁸ In such scaffolds, each layer is specifically designed to support the regeneration of a particular tissue type, mimicking the properties of the cartilage layer, bone layer and—when applied—intermediate layer. ² , ⁸ , ⁹ , ¹⁰ In equine studies, several scaffold composites have been applied, including HAP tri‐layered scaffold combined with Col1, Col2 and HyA, ² HAP bi‐ and tri‐layered scaffold combined with Mg ions and Col1, ⁸ HAP tri‐layered scaffold combined with Col (unspecified type) and HyA ¹⁰ and β‐TCP bi‐layered scaffold combined with Col1 and PLA. ⁹

In such scaffolds, both the ratio of ceramic particles to extracellular matrix (ECM) components and the specific ECM composition influence the properties of each individual layer. The cartilage layer is composed solely of ECM components, ² , ⁸ , ⁹ , ¹⁰ whereas intermediate ⁸ , ¹⁰ and bone ⁸ , ⁹ , ¹⁰ layers typically contain alloplastics incorporated in smaller and larger proportions, respectively. Among ECM components, Col1 predominates in bone tissue and contributes to its mechanical strength. It also provides numerous cell‐binding sites that enhance the adhesion and proliferation of MSC. ⁵⁶ Although its mechanical properties are not ideal for cartilage, Col1 supports short‐term chondrogenic activity ⁵⁶ and is therefore used to compose the cartilage layer (solely ⁸ , ⁹ or in combination with Col2 and HyA ² ), intermediate layer (with HyA ² or HAP ⁸ ) and bone layer (with HAP ² ). In contrast, Col2 is the primary ECM component of hyaline cartilage, contributing to its mechanical viscoelasticity, though it lacks substantial tensile strength. Col2 promotes the chondrogenic differentiation of MSCs; however, it does not provide the osteogenic signalling necessary for bone regeneration. ⁵⁶ Consequently, the use of Col2 in scaffold design is generally restricted to the chondral layer. ² However, its incorporation enhances the regeneration of hyaline cartilage, which has been demonstrated during OCD treatment by observed post‐surgery integrity of the treated joint surface. ²

4.4. Benefits of using alloplastic in cysts treatment

SCLs pose a significant therapeutic challenge, particularly when their location involves both the articular cartilage and the subchondral bone. Although conventional treatment of SCLs varies widely—from intralesional corticosteroid injection, bone cyst debridement, to cortical pin or screw placement ⁴ , ⁵ , ⁶ —the overall therapeutic aims remain consistent: to combat the inflammation within the fibrous lining of the cyst, to reduce cyst size within the subchondral bone, improve the quality of bone at the defect site and stimulate repair of the overlying articular cartilage. ¹

To date, no randomised studies have been conducted to compare different SCL treatment procedures, and there is no consensus regarding the optimal therapeutic approach. ⁶ Although Pérez‐Nogués et al. ⁴ , ⁵ compared several SCL treatment strategies, including intralesional placement of alloplastics, these studies were retrospective and primarily focused on the horses' auction value and athletic ability. They provided limited clinical data, did not state clinical inclusion criteria (e.g., lameness or joint effusion) and therefore did not demonstrate the need for treatment. Additionally, they did not report post‐treatment lameness examinations and included insufficient characterisation of the alloplastics used. Notable, only one case report ¹ and one case series study ⁶ have described an application of ceramic CP cement ¹ or composite HAP implant ⁶ for SCL filling, ¹ performed with ⁶ and without ¹ the placement of translesional pin or screw. Both studies reported satisfactory clinical outcomes ¹ , ⁶ ; however, some complications were observed. ⁶ In one case, the implant has dislodged from the bone tunnel and was radiographically identified between the bone and the overlying fascia. ⁶ In another case, radiographs taken 30 days post‐surgery revealed that the implant had been inserted too deeply. ⁶ These findings suggest that refinements in surgical procedures are still required and highlight the need for further experimental and prospective cohort studies on the use of synthetic bone substitutes in the treatment of SCLs.

A similar issue—the lack of experimental and prospective cohort studies—also applies to the treatment of ABSc using alloplastics. As with the treatment of SCLs, only one case report ¹⁵ and one case series study ¹⁶ have been published to date. These studies emphasise that a major clinical challenge in the management of ABCs is the large volume of bone required to fill the defect following debridement. ¹⁵ , ¹⁶ This poses a limitation for the use of autografts, as the amount of graft material that can be harvested from a donor site is inherently limited. ²⁵ The donor sites include the most commonly used tuber coxae, sternum, but also rib, proximal medial aspect of the tibia and proximal humerus, and harvesting is associated with additional surgical morbidity, including incisional infection possible in all harvesting sites, osteomyelitis reported particularly in the sternum and proximal tibia, pneumothorax and haemothorax when the sternum and ribs were used as donor sites or catastrophic fracture during anaesthetic recovery when the graft was obtained from the tibia or humerus. ²⁴

Therefore, the use of synthetic bone substitutes represents a promising alternative, as demonstrated by successful outcomes following intralesional placement of composite HAP sponge‐like structure scaffold ¹⁵ and ceramic β‐TCP granules. ¹⁶ Follow‐up clinical, ¹⁵ , ¹⁶ radiographical ¹⁵ and CT ¹⁵ , ¹⁶ evaluations revealed favourable clinical improvement, ¹⁵ , ¹⁶ reduction in lesion size ¹⁵ , ¹⁶ and evidence of bone remodelling. ¹⁵ However, complications were also observed. ¹⁶ In one case, an inflammatory reaction developed at the site of residual β‐TCP granules, necessitating removal of the alloplastics. Following removal, the ABC healed satisfactorily. ¹⁶

4.5. Benefits of using alloplastic in bone defect treatment

In the treatment of segmental bone defects—particularly in equine orthopaedic experimental models ¹¹ , ¹² , ¹³ , ¹⁴ —a variety range of alloplastics have been investigated for their osteoconductive ¹¹ , ¹² , ¹³ and osteoinductive ¹¹ , ¹³ potential, as well as clinical applicability. ¹¹ , ¹² , ¹³ , ¹⁴ These include ceramic CP cements, ¹³ composite CP cements, ¹⁴ composite HAP scaffolds ¹¹ and composite CC implants with unspecified structure. ¹² Each graft offers distinct biological and mechanical advantages; however, a notable advancement is the development of Mg‐doped injectable CP cement. ¹⁴

In this prospective cohort study, the Mg‐CP cement group demonstrated enhanced callus formation and greater fragment stability at the osteotomy site, suggesting superior mechanical support. ¹⁴ However, this model involved osteotomy of the second and fourth metatarsal bones, which are non‐weight‐bearing. ¹⁴ As Perrier et al. ¹³ pointed out, although the second and fourth metatarsal bones are suitable for reproducible and low‐risk defect models, they may not accurately reflect the healing environment of major weight‐bearing bones such as the third metacarpal or metatarsal bone, ¹² the femur ¹³ or the tibia. ¹³

Interestingly, among the four experimental models developed for the treatment of segmental bone defects, ¹¹ , ¹² , ¹³ three involved the fourth metacarpal bone ¹¹ or the second and fourth metatarsal bones. ¹³ , ¹⁴ The results of these studies were satisfactory, demonstrating favourable new bone formation that was more pronounced in the alloplastic groups than the controls. ¹¹ , ¹² , ¹³ In contrast, the only studies conducted on the third metacarpal bone produced opposite findings. ¹² Therefore, these results should be extrapolated to equine clinical practice with caution, considering the limitation associated with weight‐bearing effects and the limited availability of regional cancellous bone, given that the defect was created in the proximal diaphysis of the metacarpus, an area with relatively sparse cancellous bone. Consequently, further research using more clinically relevant, load‐bearing bone models is warranted.

4.6. Limitations and future directions

The main limitation of this study stems from the limited number of existing publications, particularly research articles on the use of synthetic bone substitutes in horses. This could be explained by the fact that appropriate large animal models are costly and often impractical for achieving adequate sample sizes as well as there are growing ethical concerns on horses as experimental models, which limit the number of randomised controlled trials. Among the case reports described, at least two OCD lesions ² , ³ would typically heal without the use of bone substitutes, which raises questions about the actual beneficial effect of the alloplastic material itself. Another limitation comes from a large variety of synthetic materials used both in case reports and research publications. The synthetic bone substitutes field has been ‘a hot topic’ in human bone regenerative medicine, and thus a large variety of biomaterials has been proposed to serve as bone substitutes. In this study, almost every publication described different materials, so it limited the possibility of comparing outcomes of the same material for different clinical problems. Some authors did not report precise details on the materials used—for example, declaring the use of HAP implant with no further specification ⁴ , ⁵ —which, given the variety of materials on the market, makes it impossible to detect which one was used in a particular study based on the presented data. Moreover, some studies in this systematic review lacked basic data on follow‐up and clinical examination, ³ , ⁴ , ⁵ , ⁹ , ¹⁰ , ¹¹ , ¹² which is a significant limitation of this review that affects treatment effect estimation. It is also evident that research articles show high heterogeneity in the hierarchy of evidence. Therefore, data analysis was descriptive, and meta‐analysis was not performed, which is another limitation of this systematic review.

Both veterinary and human regenerative medicine increasingly rely on bone substitute materials to manage critical‐sized defects, fractures and degenerative conditions. ⁵⁷ However, compared with veterinary medicine, a wider range of bone graft substitutes has been developed and validated in human medicine through preclinical studies ⁵⁸ , ⁵⁹ , ⁶⁰ , ⁶¹ , ⁶² , ⁶³ and extensive clinical trials. ⁶⁴ , ⁶⁵ , ⁶⁶ , ⁶⁷ These studies have also been collated and critically assessed in systematic reviews, ⁴² , ⁶⁸ which are currently lacking in the field of equine regenerative medicine. Therefore, this systematic review not only fills this gap but also proposes future directions for equine research by facilitating the translation of biomaterials originally designed for human regenerative medicine into veterinary practice, as both species share fundamental biological requirements for bone healing. ⁶⁹ Moreover, the comparatively fewer regulatory barriers in veterinary medicine compared with human medicine ⁷⁰ may enable more rapid adoption of human‐grade synthetic bone substitutes in equine applications. In human medicine, HAP is the leading alloplastic biomaterial in revision surgery ⁴² , ⁵⁸ , ⁵⁹ , ⁶⁴ ; CP and calcium sulphate dominate orthopaedic traumatology ⁴² , ⁶⁰ , ⁶⁵ , ⁶⁷ ; β‐TCP is widely used in spinal surgery ⁴² , ⁶¹ ; and synthetic polymers are the leading biomaterials in neurosurgery. ⁴² , ⁶² Given that HAP, ² , ⁴ , ⁵ , ⁶ , ⁸ , ¹⁰ , ¹¹ , ¹⁵ CP ¹ , ⁷ , ¹³ , ¹⁴ and β‐TCP ³ , ⁹ , ¹⁶ , ³² have already been applied in equine clinical and research settings, calcium sulphate, ⁶⁷ synthetic polymers ⁶² and zirconium dioxide–doped bioactive glass ⁶³ warrant further human‐to‐equine translation. In particular, HAP, CP, synthetic polymers and collagen‐based composites appear to be promising materials for 3D‐bioprinting, exhibiting diverse cell compatibility and viscosity profiles, which determine their suitability for 3D bioprinting, advantages, limitations and potential applications. ⁴² , ⁵⁸ , ⁵⁹ , ⁶⁵ , ⁷¹ Potentially, 3D‐printed bone scaffolds may find application in advanced treatments of equine bone diseases, for example, critical bone defects. Therefore, we hope that outlining these general trends will help guide future research and accelerate progress in equine regenerative medicine.

5. CONCLUSIONS

In equine medicine, HAP, CP and β‐TCP were the leading alloplastic biomaterials applied clinically and experimentally. In case reports, both ceramics and composites were used; however, in research studies, composites were the predominant alloplastic materials. Bi‐ and tri‐layered scaffolds were employed to fill chondral and osteochondral defects—both naturally occurring in the SCL and experimentally induced—and, less frequently, cements or granules were used. Conversely, cements were mainly applied to enhance bone healing capacity—particularly in segmental bone defects—and scaffolds were used less often. When applied alone, alloplastics demonstrated osteoconductive and osteoinductive properties. Nevertheless, the addition of biologically active additives derived from autologous bone marrow further enhanced their biological properties, providing osteogenic and, in some cases, chondrogenic effects. Treatment outcomes were generally favourable, although clinical evaluation in some studies was inconsistent or incomplete. Structural healing of treated cartilage and bone was effectively monitored using ultrasonography/arthroscopy and radiography/CT, respectively. Experimental studies supported by histological assessment revealed that, when alloplastics were applied, the regenerated cartilage and bone tissue exhibited a structure similar to that of native tissue. However, the greater new bone formation observed during the healing of segmental bone defects in alloplastic‐treated groups compared with controls should be extrapolated to the equine clinical practice with caution, considering the limitations associated with weight‐bearing effects. These findings suggest that the use of alloplastics in horses may be particularly beneficial for the treatment of bone diseases.

FUNDING INFORMATION

The publication was (co)financed by Science development fund of the Warsaw University of Life Sciences—SGGW.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflicts of interest.

AUTHOR CONTRIBUTIONS

Katarzyna Skierbiszewska: Conceptualization; investigation; methodology; writing – review and editing; writing – original draft; formal analysis; data curation. Bernard Turek: Formal analysis; validation; writing – original draft; writing – review and editing; supervision. Tomasz Jasiński: Conceptualization; investigation; methodology; formal analysis; writing – original draft; writing – review and editing. Michał Kaczorowski: Formal analysis; writing – original draft; writing – review and editing. Natalia Kozłowska: Formal analysis; writing – original draft; writing – review and editing. Julia Higuchi: Formal analysis; writing – original draft; writing – review and editing. Małgorzata Domino: Conceptualization; investigation; writing – original draft; writing – review and editing; visualization; project administration; formal analysis; methodology.

DATA INTEGRITY STATEMENT

No new data were created or analysed in this study.

ETHICAL ANIMAL RESEARCH

Not applicable.

Supporting information

Data S1: An example of data extraction template.

Table S1: Summary of records on equine bone graft related to equine stem cells.

Table S2: Summary of records on equine bone autografts.

Table S3: Summary of records on equine bone allografts.

Table S4: Summary of records on equine bone xenografts.

Table S5: Summary of records on equine bone nonresorbable grafts.

Table S6: Summary of records on equine bone alloplastics. Records included in this systematic review are marked with an asterisk (*).

Table S7: Search records.

Text S1: Search strategies and search strings.

DATA AVAILABILITY STATEMENT

Data sharing is not applicable to this article as no new data were created or analysed in this study.