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Dr. Matthias Schlund

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Linkedin biotis-bordeaux

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33 (0)5 57 57 14 88

Bioingénierie Tissulaire (BioTis)

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Batiment BBS (Bordeaux Biologie Santé), 5e étage

2, rue du Dr Hoffmann Martinot,

33000, Bordeaux, France

Mailing Address:

Université de Bordeaux, Campus Carreire

146, rue Léo Saignat, Case 84,

33076, Bordeaux Cedex, France

Tissular integration and material biocompatibility

Abstract

Reference

Project Leader

The use of autologous tissue for reconstructing a defect is associated with well-recognized issues. Harvesting autologous tissue causes morbidity at the donor site, which becomes a secondary operative site with risks of functional consequences and complications. Furthermore, autologous tissue requires a molding period to adapt to the recipient area. In contrast, the use of alloplastic materials for reconstruction offers numerous advantages. Many alloplastic materials are used daily in cranio-maxillofacial surgery, particularly in trauma and the reconstruction of defects: metallic materials (especially titanium), ceramics (calcium-phosphate ceramics, bioglass), and polymers (silicone, porous polyethylene, polyether-ether-ketone, methyl methacrylate, polydioxanone, etc.) [1,4].

▷[1] Hsieh TY, Dhir K, Binder WJ, Hilger PA. Alloplastic Facial Implants. Facial Plast Surg. déc 2021;37(6):741‑50.

▷[2] Zanotti B, Zingaretti N, Verlicchi A, Robiony M, Alfieri A, Parodi PC. Cranioplasty: Review of Materials. J Craniofac Surg. nov 2016;27(8):2061‑72.

▷[3] Dubois L, Steenen SA, Gooris PJJ, Bos RRM, Becking AG. Controversies in orbital reconstruction-III. Biomaterials for orbital reconstruction: a review with clinical recommendations. Int J Oral Maxillofac Surg. janv 2016;45(1):41‑50.

▷[4] Bourry M, Hardouin JB, Fauvel F, Corre P, Lebranchu P, Bertin H. Clinical evaluation of the efficacy of materials used for primary reconstruction of orbital floor defects: Meta-analysis. Head Neck. févr 2021;43(2):679‑90.

▷[5] Thrivikraman G, Athirasala A, Twohig C, Boda SK, Bertassoni LE. Biomaterials for Craniofacial Bone Regeneration. Dent Clin North Am. oct 2017;61(4):835‑56.

▷[6] Henry J, Amoo M, Taylor J, O’Brien DP. Complications of Cranioplasty in Relation to Material: Systematic Review, Network Meta-Analysis and Meta-Regression. Neurosurgery. 16 août 2021;89(3):383‑94.

▷[7] Axmann S, Paridaens D. Anterior surface breakdown and implant extrusion following secondary alloplastic orbital implantation surgery. Acta Ophthalmol. mai 2018;96(3):310‑3.

▷[8] Grob S, Yonkers M, Tao J. Orbital Fracture Repair. Semin Plast Surg. févr 2017;31(1):31‑9.

▷[9] Rayess HM, Svider P, Hanba C, Patel VS, Carron M, Zuliani G. Adverse Events in Facial Implant Surgery and Associated Malpractice Litigation. JAMA Facial Plast Surg. 1 mai 2018;20(3):244‑8.

▷[10] Kholaki O, Hammer DA, Schlieve T. Management of Orbital Fractures. Atlas Oral Maxillofac Surg Clin North Am. 2019;27(2):157‑65.

▷[11] Lee HBH, Nunery WR. Orbital adherence syndrome secondary to titanium implant material. Ophthalmic Plast Reconstr Surg. févr 2009;25(1):33‑6.

▷[12] Dubois L, Steenen SA, Gooris PJJ, Mourits MP, Becking AG. Controversies in orbital reconstruction--II. Timing of post-traumatic orbital reconstruction: a systematic review. Int J Oral Maxillofac Surg. avr 2015;44(4):433‑40.

▷[13] L’Heureux N, McAllister TN, de la Fuente LM. Tissue-engineered blood vessel for adult arterial revascularization. N Engl J Med. 4 oct 2007;357(14):1451‑3.

▷[14] Magnan L, Kawecki F, Labrunie G, Gluais M, Izotte J, Marais S, et al. In vivo remodeling of human cell-assembled extracellular matrix yarns. Biomaterials. juin 2021;273:120815.

They eliminate the need for autologous tissue harvesting, thus avoiding donor-site morbidity and significantly reducing operative time. Additionally, these materials can be machined to be pre-shaped for a given recipient site, improving both precision and efficiency. They can even be custom-made from imaging of the patient’s defect, maximizing accuracy and saving operative time [2,5].

However, the limited biocompatibility of many biomaterials remains a serious obstacle to their long-term success in numerous applications. Indeed, alloplastic materials—even those considered biocompatible—induce a chronic inflammatory reaction known as a “foreign-body response,” which may lead to scar fibrosis, functional impairment, or even reconstruction failure with implant “rejection” [3,6,8]. These complications often require complex and costly secondary procedures, performed in a compromised environment with increased scarring and infection risks [9]. Autologous tissue, by contrast, is by definition fully biocompatible, as its implantation triggers minimal inflammatory reaction. Moreover, unlike synthetic implants, living tissue can perform biological functions, be remodeled by host cells, and does not create a site susceptible to infection.

Orbital fractures are a good example of this issue. These fractures behave differently from “typical” fractures. The orbit is a cavity with immobile walls, making the classical algorithm of fracture treatment—reduction and fixation—poorly suited. A nondisplaced orbital fracture with no functional consequences requires no treatment. Conversely, a displaced fracture will cause functional disturbances (diplopia, restricted ocular movements) and morphological changes (loss of globe projection or enophthalmos) due to herniation of orbital tissues through the fracture into adjacent cavities (the maxillary sinus for the orbital floor, the nasal cavity for the medial wall). Management relies on repositioning the orbital contents into the orbit and reconstructing the orbital wall. This reconstruction was traditionally performed using autologous tissue: bone, cartilage, fascia, periosteum, or even biological tissue of allogenic or xenogenic origin. Today, orbital wall reconstruction is most often achieved using an alloplastic material [3]. The type of material varies widely between teams and countries [3]. Unfortunately, some patients develop an uncontrolled inflammatory response that becomes chronic (lasting years) and results in thick fibrosis, leading to diplopia from extraocular muscle restriction or enophthalmos due to tissue retraction [8,10]. In polymer implants, excessive fibrosis can even cause secondary implant displacement. Titanium offers excellent biocompatibility, but tissues often incorporate firmly into the material, once again leading to retraction or adhesions with restricted muscle movement [3,11]. Secondary reconstructions in these cases are very challenging due to difficult dissection. Even primary orbital reconstruction after fracture does not guarantee a perfectly predictable result. An anatomically perfect reconstruction does not ensure a functionally or morphologically perfect outcome because of the cicatricial evolution of the orbital soft tissues [12]. The need for secondary procedures should therefore not be underestimated. Furthermore, when the bony anatomy is properly restored, the role of soft tissues in outcome deterioration becomes predominant. Developing strategies to limit and control cicatricial fibrosis therefore appears to be a particularly relevant objective.

The Cell-Assembled extracellular Matrix (CAM) is a biological membrane synthesized in vitro by human dermal fibroblasts. This membrane has already been used in the bioengineered fabrication of vascular grafts successfully implanted into the human arterial circulation [13]. Entirely biological and non-denatured by chemical treatments, the membrane is “accepted” by the host and does not cause chronic inflammatory reaction after implantation [14]. It therefore does not resorb but is instead remodeled very slowly. The CAM is ideally suited to cover a more solid material. Our strategy is thus to provide a thin, uniform cicatricial envelope to avoid unpredictable and heterogeneous fibrotic responses. By masking the material from the host’s immune cells, the CAM should prevent foreign-body inflammatory reactions and thereby uncontrolled fibrosis or soft-tissue adhesions. Moreover, it would create a cleavage plane that facilitates dissection if secondary reconstruction becomes necessary.

Our project therefore aims to evaluate this innovative strategy by implanting various alloplastic materials known to induce inflammatory reactions, either covered or not covered with CAM, in an in vivo rat model.