1968

• Sullivans & Atkins

  First systematic description of gingival grafting, including healing mechanisms, and set the foundation for modern soft tissue grafting techniques in periodontics and implantology.

  

1969

1970

1971

1972

1973

1974

1975

• Karring et al

  Landmark study that demonstrated that connective tissue dictates the phenotype of overlying epithelium in the oral mucosa.

  

1976

• Melcher

  Introduction of the concept of "compartmentalization" in the literature, which was fundamental for the development of periodontal regenerative therapies.

  

1977

1978

1979

• Listgarten & Rosenberg

  A histological investigation of human periodontal tissues following reattachment procedures provided critical insight into the healing and reformation processes after periodontitis-induced damage, enhancing our biological understanding of periodontal regeneration.

  

1980

• Caton et al

  A comparative histological study evaluating the influence of four different regenerative procedures on connective tissue attachment levels highlighted key variations in regenerative outcomes.

  

1980

• Karring et al

  An early experimental study assessing the healing potential of periodontitis-affected roots implanted into bone revealed that diseased tissues retain regenerative capacity under certain conditions, supporting the foundational concept of GTR and the importance of the healing environment.

  

1981

1982

• Nyman et al

  One of the first clinical studies in humans to clearly report new attachment formation following surgery, this study provided early clinical validation for the GTR concept.

  

1983

1984

• Gottlow et al

  A landmark paper that explicitly introduced the term Controlled Tissue Regeneration, demonstrating that tissue healing could be actively regulated through the use of barrier membranes—marking a conceptual turning point.

  

1985

• Karring et al

  A follow-up in vivo study providing experimental evidence for Melcher’s hypothesis, confirming that PDL cells can guide true regeneration of periodontal structures.

  

1986

• Gottlow et al

  One of the earliest clinical case reports applying GTR in humans, demonstrating that barrier membranes can promote new attachment formation, thereby translating theory into practice.

  

1987

• Nyman et al

  A landmark histological study confirming that new cementum, PDL, and bone could form following GTR in humans, offering definitive biological proof of true periodontal regeneration.

  

1988

• Dahlin et al

  The first animal study to successfully apply GTR principles to bone defects rather than the periodontium, representing the origin of the concept of Guided Bone Regeneration (GBR).

  

1989

• Bowers et al

  A pivotal human study evaluating multiple surgical regenerative techniques, verifying their ability to reconstitute the full new attachment apparatus, including cementum, PDL, and alveolar bone.

  

1990

• Wikesjö & Nilvéus

  A classic study highlighting the importance of wound stability, particularly the blood clot,s for regenerative success.

  

1991

1992

1993

1994

• Schenk et al

  An experimental study describing the bone healing pattern,confirming the original hypothesis of GBR that membrane coverage of bone defects creates a suitable environment—referred to as a secluded space—for bone regeneration.

  

1995

• Sigurdsson et al

  The study evaluated bone and cementum regeneration following periodontal reconstructive surgery using recombinant human bone morphogenetic protein-2 in a beagle dog model.

  

1996

1997

• Zitzmann et al

  One of the earliest clinical studies comparing biodegradable collagen membranes versus ePTFE membrane.

  

1997

• Heijl et al

  The first pivotal clinical trial demonstrating the effectiveness of Enamel Matrix Derivative (EMD/EMDOGAIN®) in humans, marking a shift from physical barrier-based therapy to biologically mediated regeneration.

  

1998

1999

• Sculean et al

  One of the first controlled clinical trials to directly compare GTR and EMD under the same conditions, providing valuable evidence for selecting between two major regenerative therapies.

  

2000

• Bartold et al

  The paper explains the roles of different cells—like fibroblasts, immune cells, and epithelial cells—in tissue health, inflammation, healing, and periodontal regeneration. The difference between regeneration and reconstruction and why understanding the tissues and molecular pathways involved is key to achieving predictable outcomes are well described.

  

2001

• Guiha et al

  This study demonstrated that subepithelial connective tissue grafts undergo rapid and complete revascularization from the periodontal and supraperiosteal plexuses, with limited evidence of new bone or cementum formation.

  

2001

• Goldstein et al

  The first human histological evidence of new connective tissue attachmentn following root coverage with a subepithelial connective tissue graft, confirming true periodontal regeneration.

  

2002

2003

• Berglundh et al

  A landkmark paper describing the healing sequence that leads to implant osseointegration.

  

2003

• Nevins et al

  The first human histological evidence that the use of rhPDGF-BB combined with bone allograft promotes periodontal regeneration in Class II furcation defects.

  

2003

• Donos et al

  Preclinical histological evidence showing periodontal regeneration—including new cementum with inserting collagen fibers and significant bone fill—following GTR and/or enamel matrix derivative in surgically created degree III furcation defects in monkeys.

  

2004

• Abrahamsson et al

  A landmark paper describing the healing sequence that leads to implant osseointegration on different implant surfaces.

  

2004

• Wikesjö et al

  One of the preclinical studies supporting the use of rhBMP for enhanced bone formation.

  

2004

• Seo et al

  This study laid the groundwork for biologically advanced, cell-based regenerative therapies beyond conventional biomaterials or growth factors.

  

2005

• Araújo & Lindhe

  One of the earliest preclinical studies demonstrating thin buccal bone wall undergoes rapid resorption with over 2 mm of vertical loss after tooth extraction.

  

2005

• Graziani et al

  An animal study confirming that periodontal healing following GTR in recession-type defects can lead to long-term complete periodontal regeneration.

  

2006

2007

2008

2009

• Araújo & Lindhe

  A foundational study showing that tooth extraction is not merely a surgical procedure but a biological turning point, emphasizing the importance of flapless, minimally invasive techniques to preserve ridge architecture and enhance regenerative outcomes.

  

2010

2011

2012

• Miron et al

  An in vivo study investigating how different autogenous bone harvesting techniques influence the release of growth factors.

  

2012

• Liu et al

  An in vitro study showing that mesenchymal stem cells derived from inflamed periodontal ligaments have impaired immunomodulatory function, highlighting the impact of inflammatory conditions on stem cell-based periodontal regeneration.

  

2012

• Nunez et al

  Preclinical study demonstrating that implantation of cementum- or PDL-derived cells promotes true periodontal regeneration, including new cementum and connective tissue attachment, in canine intrabony defects.

  

2013

• Dickinson et al

  This study provides a detailed temporal mapping of early periodontal wound healing and regeneration, clarifying the rapid cellular events that shape regenerative outcomes.

  

2014

2015

2016

2017

2018

2019

• Gruber

  The impact of immune cells on bone regeneration is presumably a way to reinitiate the developmental mechanisms of intramembranous and endochondral bone formation.