Evaluation of an injectable rhGDF-5/PLGA construct for minimally invasive periodontal regenerative procedures: a histological study in the dog

• Published in: Journal of clinical periodontology Vol. 37; no. 4; pp. 390 - 397
• Main Authors: Kwon, David H., Bennett, William, Herberg, Samuel, Bastone, Patrizia, Pippig, Susanne, Rodriguez, Nancy A., Susin, Cristiano, Wikesjö, Ulf M. E.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2010; Blackwell
• Subjects: Absorbable Implants; Alveolar Bone Loss - etiology; Alveolar Bone Loss - therapy; Animals; Biocompatible Materials - administration & dosage; Biological and medical sciences; Biotechnology; bone; cementum; Dentistry; Disease Models, Animal; Dogs; Drug Carriers - administration & dosage; Facial bones, jaws, teeth, parodontium: diseases, semeiology; Fundamental and applied biological sciences. Psychology; GDF-5; Growth Differentiation Factor 5 - administration & dosage; Growth Differentiation Factor 5 - physiology; Guided Tissue Regeneration, Periodontal - methods; Health. Pharmaceutical industry; Humans; Industrial applications and implications. Economical aspects; Injections, Intralesional; Lactic Acid - administration & dosage; Male; Mandible - drug effects; Mandible - surgery; Medical sciences; Miscellaneous; Non tumoral diseases; Otorhinolaryngology. Stomatology; periodontal ligament; Periodontal Pocket - complications; Periodontal Pocket - drug therapy; periodontal regeneration; Periodontium - drug effects; Periodontium - physiology; PLGA; Polyglycolic Acid - administration & dosage; Recombinant Proteins; tissue engineering; Tissue Scaffolds; Glycolic acid copolymer; Fissipedia; Evaluation; Carnivora; Lactone copolymer; Tissue engineering; Lactic acid copolymer; Histology; Dentistry; Injection; Regeneration; Invasive procedure; Vertebrata; Periodontal ligament; periodontal regeneration; Mammalia; PLGA; Animal; GDF-5; Bone; Dog; Cementum
• ISSN: 0303-6979; 1600-051X
• DOI: 10.1111/j.1600-051X.2010.01546.x

Kwon DH, Bennett W, Herberg S, Bastone P, Pippig S, Rodriguez NA, Susin C, Wikesjö UME. Evaluation of an injectable rhGDF‐5/PLGA construct for minimally invasive periodontal regenerative procedures: a histological study in the dog. J Clin Periodontol 2010; 37: 390–397. doi: 10.1111/j.1600‐051X.2010.01546.x. Aim: To evaluate the injectability, biocompatibility, safety, and periodontal wound healing/regeneration following application of a novel bioresorbable recombinant human growth/differentiation factor‐5 (rhGDF‐5)/poly(lactic‐co‐glycolic acid) (PLGA) construct. Material and Methods: Periodontal pockets (3 × 6 mm, width × depth) were surgically created over the buccal roots of the second and fourth mandibular pre‐molars in eight adult Hound Labrador mongrel dogs. Surgeries including injection of the rhGDF‐5/PLGA construct into the pockets were sequenced that four animals provided 2‐/4‐week and four animals 6‐/8‐week observations of sites receiving rhGDF‐5/PLGA or serving as sham‐surgery control. Results: The rhGDF‐5/PLGA construct was easy to prepare and apply. Approximately 0.2 ml (93 μg rhGDF‐5)/tooth was used. Clinical and radiographic healing was exemplary without adverse events. Healing was characterized by a non‐specific connective tissue attachment, acellular/cellular cementum, periodontal ligament (PDL), bone regeneration, and a junctional epithelium. PLGA fragments were observed in 4/7, 2/8, and 1/8 sites at 2, 4, and 6 weeks, respectively. Associated inflammatory reactions exhibited no limiting effect on periodontal wound healing/regeneration. Root resorption/ankylosis was not observed. Bone formation showed apparent increased maturity (lamellar bone) at 6 weeks in sites receiving rhGDF‐5/PLGA compared with the control. Both protocols exhibited significant increases in PDL, cementum, and bone regeneration over time, without significant differences between treatments. In time, PDL and cementum regeneration was twofold greater for the control at 4 weeks (p=0.04) while increased bone formation was observed at sites receiving rhGDF‐5/PLGA (p<0.01). Conclusions: In conclusion, the rhGDF‐5/PLGA construct appears to be a safe technology for injectable, ease‐of‐use application of rhGDF‐5‐stimulated periodontal wound healing/regeneration. Additional work to optimize the polymer carrier and rhGDF‐5 release kinetics/dose might be required before evaluating the efficacy of this technology in clinical settings using minimally invasive approaches.