Osteochondral scaffolds for early treatment of cartilage defects in osteoarthritic joints: from bench to clinic

doi:10.3877/cma.j.issn.2096-112X.2020.01.002

Biomaterials Translational ›› 2020, Vol. 1 ›› Issue (1): 3-17.doi: 10.3877/cma.j.issn.2096-112X.2020.01.002

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Osteochondral scaffolds for early treatment of cartilage defects in osteoarthritic joints: from bench to clinic

Maryam Tamaddon¹, Helena Gilja¹, Ling Wang², J. Miguel Oliveira³^,⁴^,⁵, Xiaodan Sun⁶, Rongwei Tan⁷, Chaozong Liu¹^,^*()

1 Institute of Orthopaedic & Musculoskeletal Science, University College London, Royal National Orthopaedic Hospital, London, UK
2 State Key Laboratory for Manufacturing System Engineering, School of Mechanical Engineering, Xi’an Jiaotong University, Xi’an, Shaanxi Province, China
3 3B’s Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Portugal
4 ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal
5 The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Avepark, Portugal
6 School of Materials Science and Engineering, Tsinghua University, Beijing, China
7 Shenzhen Lando Biomaterials Co. Ltd. Merchants Guangming Science Park, Shenzhen, Guangdong Province, China

Received:2020-06-30 Revised:2020-09-14 Accepted:2020-09-25 Online:2020-12-28 Published:2020-12-28
Contact: Chaozong Liu E-mail:chaozong.liu@ucl.ac.uk

Abstract

Abstract:

Osteoarthritis is a degenerative joint disease, typified by the loss in the quality of cartilage and bone at the interface of a synovial joint, resulting in pain, stiffness and reduced mobility. The current surgical treatment for advanced stages of the disease is joint replacement, where the non-surgical therapeutic options or less invasive surgical treatments are no longer effective. These are major surgical procedures which have a substantial impact on patients’ quality of life and lifetime risk of requiring revision surgery. Treatments using regenerative methods such as tissue engineering methods have been established and are promising for the early treatment of cartilage degeneration in osteoarthritis joints. In this approach, 3-dimensional scaffolds (with or without cells) are employed to provide support for tissue growth. However, none of the currently available tissue engineering and regenerative medicine products promotes satisfactory durable regeneration of large cartilage defects. Herein, we discuss the current regenerative treatment options for cartilage and osteochondral (cartilage and underlying subchondral bone) defects in the articulating joints. We further identify the main hurdles in osteochondral scaffold development for achieving satisfactory and durable regeneration of osteochondral tissues. The evolution of the osteochondral scaffolds - from monophasic to multiphasic constructs - is overviewed and the osteochondral scaffolds that have progressed to clinical trials are examined with respect to their clinical performances and their potential impact on the clinical practices. Development of an osteochondral scaffold which bridges the gap between small defect treatment and joint replacement is still a grand challenge. Such scaffold could be used for early treatment of cartilage and osteochondral defects at early stage of osteoarthritis and could either negate or delay the need for joint replacements.

Key words: cartilage injury, osteoarthritis, osteochondral scaffold, regenerative medicine, subchondral defect, tissue engineering

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Grade	Description of changes
Grade 0	No changes
Grade I	Doubtful narrowing of the joint space and possible osteophytic lipping
Grade II	Definite osteophytes and possible narrowing of the joint space
Grade III	Moderate multiple osteophytes, definite narrowing of the joint space, and some sclerosis, and possible deformity of the bone ends
Grade IV	Large osteophytes marked narrowing of the joint space, severe sclerosis, and definite deformity of the bone ends

Grade	Description of changes
Grade 0	No changes
Grade I	Doubtful narrowing of the joint space and possible osteophytic lipping
Grade II	Definite osteophytes and possible narrowing of the joint space
Grade III	Moderate multiple osteophytes, definite narrowing of the joint space, and some sclerosis, and possible deformity of the bone ends
Grade IV	Large osteophytes marked narrowing of the joint space, severe sclerosis, and definite deformity of the bone ends

Grade	Description of changes
Grade 0	Normal	-
Grade 1	Nearly normal	Superficial lesions. Soft indentation and/or superficial fissures and cracks
Grade 2	Abnormal	Lesions extending down to < 50% of cartilage depth
Grade 3	Severely abnormal	Cartilage defects extending down > 50% of cartilage depth as well as down to calcified layer and down to but not through the subchondral bone. Blisters are included in this Grade
Grade 4	Severely abnormal	Osteochondral injuries, lesions extending to the subchondral bone plate or deeper into the trabecular bone

Grade	Description of changes
Grade 0	Normal	-
Grade 1	Nearly normal	Superficial lesions. Soft indentation and/or superficial fissures and cracks
Grade 2	Abnormal	Lesions extending down to < 50% of cartilage depth
Grade 3	Severely abnormal	Cartilage defects extending down > 50% of cartilage depth as well as down to calcified layer and down to but not through the subchondral bone. Blisters are included in this Grade
Grade 4	Severely abnormal	Osteochondral injuries, lesions extending to the subchondral bone plate or deeper into the trabecular bone

Structure	Device	Materials	References
Biphasic	Agili-C^TM (CartiHeal, Tel Aviv, Israel)	Aragonite-hyaluronate biphasic scaffold. Thin hyaluronate covered cartilage phase, overlying a thick bone phase	Kon et al.⁷⁸
	TruFitTM (Smith and Nephew, USA)	Chondral phase: PLGA, osseous phase: calcium sulfate and PGA fibres	Carmont et al.^79-84
	Chondro-mimetic (Collagen Solutions, UK)	Chondral phase: Collagen-GAG;	Getgood et al.⁸⁵
	Chondro-mimetic (Collagen Solutions, UK)	Osseous layer: Collagen, GAG, CP	Getgood et al.⁸⁵
	Biphasic	Chondral phase: PLGA;	Chiang et al.⁸⁶
	Biphasic	Osseous phase: PLGA-TCP, made by particulate leaching method	Chiang et al.⁸⁶
	Chondro-Gide	Bilayered collagen I/III scaffold	Kusano et al.^87-89
Multiphasic	MaioRegen^® (Fin-Ceramica Faenza S.p.A., Italy)	Chondral phase: Type I equine collagen;	Kon et al.^90-96
		Intermediate phase: Type I collagen (60%) and Mg-enriched HA (40%);
		Osseous phase: A mineralised blend of type I collagen (30%) and 70% of Mg-enriched HA

Osteochondral scaffolds for early treatment of cartilage defects in osteoarthritic joints: from bench to clinic

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No.	Study title	Identifier No.	Submission date	Status/sponsor	Conditions	Intervention/follow up/results
1	Clinical and Radiological Results of Osteochondral (OC) Repair Using MaioRegen in Knee and Ankle Surgery	NCT02345564	11-Sep-14	Unknown/Barmherzige Brüder Eisenstadt	OC lesion of talus degenerative lesion of articular cartilage of knee; size 2-4 cm²	MaioRegen/18 months/no results posted
2	A Prospective, Post-marketing Registry on the Use of ChondroMimetic for the Repair of OCDs	NCT01209390	6-Aug-10	Terminated (slow recruitment rate)/TiGenix n.v.	OCDs knee, less than 12 mm diameter and 8 mm depth	Chondromimetic device/6, 12, 24, 36 months/no results posted
3	Study for the Treatment of Knee Chondral and OC Lesions	NCT01282034	21-Jan-11	Completed Feb 2016/FinCeramica Faenza Spa	Chondral and OC knee lesions; Grades III/IV outerbridge, 2-9 cm²	MaioRegen/6, 12, 24 months/no results posted
4	Repair of articular OCD	NCT01409447	3-Aug-11	Unknown/National Taiwan University Hospital	Osteochondritis dissecans knee, less than 3 cm	BiPhasic/-/no results posted
5	Chondrofix OC allograft prospective study	NCT01410136	2-Aug-11	Terminated/Zimmer Orthobiologics, Inc.	Articular cartilage disorder, degeneration, defect and acute injury; Up to two cartilage lesion, each measuring less than 8 cm²	Chondrofix OC allograft/24 up to 60 months/no results posted
6	Agili-C^TM Implant Performance Evaluation in the Repair of Cartilage and OCDs	NCT02423629	3-Dec-14	Completed/Cartiheal (2009) Ltd.	Cartilage or OCD of the knee, ICRS Grade III or above, 1-7 cm²	Agili-C/6, 12, 18, 24 months/no results posted
7	BiPhasic Cartilage Repair Implant (BiCRI) IDE Clinical Trial - Taiwan	NCT01477008	14-Nov-11	Active, not recruiting/BioGend Therapeutics Co. Ltd.	Chondral and OCD of femoral condyles and trochlea; ICRS grade 3-4 lesion, Outerbridge grade 4, or OCD grades 3-4, 12.5 mm diameter with one implant or if larger with two implants	BiPhasic Cartilage Implant/preop, 6 weeks, 3, 6 and 12 months/no results posted
8	Evaluation of the Agili-C Biphasic Implant in the Knee Joint	NCT01471236	10-Nov-11	Completed/Cartiheal (2009) Ltd.	Cartilage diseases, osteochondritis dissecans, less than 2 cm² and 3 mm depth	Agili-C/3, 6, 9, 12, 18, 24 months/no results posted
9	Pivotal Study to Evaluate the Safety and Efficacy of GelrinC for Treatment of Cartilage Defects	NCT03262909	17-Aug-17	Recruiting/Regentis Biomaterials	Knee joint cartilage defects, ICRS III or IV, lesion size between 1 and 5 cm² post debridement, less than or equal to 2.5 cm in diameter	GelrinC/24 months/no results posted

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